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Sample records for association study analysis

  1. Multivariate Methods for Meta-Analysis of Genetic Association Studies.

    Science.gov (United States)

    Dimou, Niki L; Pantavou, Katerina G; Braliou, Georgia G; Bagos, Pantelis G

    2018-01-01

    Multivariate meta-analysis of genetic association studies and genome-wide association studies has received a remarkable attention as it improves the precision of the analysis. Here, we review, summarize and present in a unified framework methods for multivariate meta-analysis of genetic association studies and genome-wide association studies. Starting with the statistical methods used for robust analysis and genetic model selection, we present in brief univariate methods for meta-analysis and we then scrutinize multivariate methodologies. Multivariate models of meta-analysis for a single gene-disease association studies, including models for haplotype association studies, multiple linked polymorphisms and multiple outcomes are discussed. The popular Mendelian randomization approach and special cases of meta-analysis addressing issues such as the assumption of the mode of inheritance, deviation from Hardy-Weinberg Equilibrium and gene-environment interactions are also presented. All available methods are enriched with practical applications and methodologies that could be developed in the future are discussed. Links for all available software implementing multivariate meta-analysis methods are also provided.

  2. MetaGenyo: a web tool for meta-analysis of genetic association studies.

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    Martorell-Marugan, Jordi; Toro-Dominguez, Daniel; Alarcon-Riquelme, Marta E; Carmona-Saez, Pedro

    2017-12-16

    Genetic association studies (GAS) aims to evaluate the association between genetic variants and phenotypes. In the last few years, the number of this type of study has increased exponentially, but the results are not always reproducible due to experimental designs, low sample sizes and other methodological errors. In this field, meta-analysis techniques are becoming very popular tools to combine results across studies to increase statistical power and to resolve discrepancies in genetic association studies. A meta-analysis summarizes research findings, increases statistical power and enables the identification of genuine associations between genotypes and phenotypes. Meta-analysis techniques are increasingly used in GAS, but it is also increasing the amount of published meta-analysis containing different errors. Although there are several software packages that implement meta-analysis, none of them are specifically designed for genetic association studies and in most cases their use requires advanced programming or scripting expertise. We have developed MetaGenyo, a web tool for meta-analysis in GAS. MetaGenyo implements a complete and comprehensive workflow that can be executed in an easy-to-use environment without programming knowledge. MetaGenyo has been developed to guide users through the main steps of a GAS meta-analysis, covering Hardy-Weinberg test, statistical association for different genetic models, analysis of heterogeneity, testing for publication bias, subgroup analysis and robustness testing of the results. MetaGenyo is a useful tool to conduct comprehensive genetic association meta-analysis. The application is freely available at http://bioinfo.genyo.es/metagenyo/ .

  3. Multivariate Meta-Analysis of Genetic Association Studies: A Simulation Study.

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    Binod Neupane

    Full Text Available In a meta-analysis with multiple end points of interests that are correlated between or within studies, multivariate approach to meta-analysis has a potential to produce more precise estimates of effects by exploiting the correlation structure between end points. However, under random-effects assumption the multivariate estimation is more complex (as it involves estimation of more parameters simultaneously than univariate estimation, and sometimes can produce unrealistic parameter estimates. Usefulness of multivariate approach to meta-analysis of the effects of a genetic variant on two or more correlated traits is not well understood in the area of genetic association studies. In such studies, genetic variants are expected to roughly maintain Hardy-Weinberg equilibrium within studies, and also their effects on complex traits are generally very small to modest and could be heterogeneous across studies for genuine reasons. We carried out extensive simulation to explore the comparative performance of multivariate approach with most commonly used univariate inverse-variance weighted approach under random-effects assumption in various realistic meta-analytic scenarios of genetic association studies of correlated end points. We evaluated the performance with respect to relative mean bias percentage, and root mean square error (RMSE of the estimate and coverage probability of corresponding 95% confidence interval of the effect for each end point. Our simulation results suggest that multivariate approach performs similarly or better than univariate method when correlations between end points within or between studies are at least moderate and between-study variation is similar or larger than average within-study variation for meta-analyses of 10 or more genetic studies. Multivariate approach produces estimates with smaller bias and RMSE especially for the end point that has randomly or informatively missing summary data in some individual studies, when

  4. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    DEFF Research Database (Denmark)

    Evangelou, Evangelos; Kerkhof, Hanneke J; Styrkarsdottir, Unnur

    2014-01-01

    Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.......Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects....

  5. Data analysis in the post-genome-wide association study era

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    Qiao-Ling Wang

    2016-12-01

    Full Text Available Since the first report of a genome-wide association study (GWAS on human age-related macular degeneration, GWAS has successfully been used to discover genetic variants for a variety of complex human diseases and/or traits, and thousands of associated loci have been identified. However, the underlying mechanisms for these loci remain largely unknown. To make these GWAS findings more useful, it is necessary to perform in-depth data mining. The data analysis in the post-GWAS era will include the following aspects: fine-mapping of susceptibility regions to identify susceptibility genes for elucidating the biological mechanism of action; joint analysis of susceptibility genes in different diseases; integration of GWAS, transcriptome, and epigenetic data to analyze expression and methylation quantitative trait loci at the whole-genome level, and find single-nucleotide polymorphisms that influence gene expression and DNA methylation; genome-wide association analysis of disease-related DNA copy number variations. Applying these strategies and methods will serve to strengthen GWAS data to enhance the utility and significance of GWAS in improving understanding of the genetics of complex diseases or traits and translate these findings for clinical applications. Keywords: Genome-wide association study, Data mining, Integrative data analysis, Polymorphism, Copy number variation

  6. Gene set-based analysis of polymorphisms: finding pathways or biological processes associated to traits in genome-wide association studies

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    Medina, Ignacio; Montaner, David; Bonifaci, Nuria; Pujana, Miguel Angel; Carbonell, José; Tarraga, Joaquin; Al-Shahrour, Fatima; Dopazo, Joaquin

    2009-01-01

    Genome-wide association studies have become a popular strategy to find associations of genes to traits of interest. Despite the high-resolution available today to carry out genotyping studies, the success of its application in real studies has been limited by the testing strategy used. As an alternative to brute force solutions involving the use of very large cohorts, we propose the use of the Gene Set Analysis (GSA), a different analysis strategy based on testing the association of modules of functionally related genes. We show here how the Gene Set-based Analysis of Polymorphisms (GeSBAP), which is a simple implementation of the GSA strategy for the analysis of genome-wide association studies, provides a significant increase in the power testing for this type of studies. GeSBAP is freely available at http://bioinfo.cipf.es/gesbap/ PMID:19502494

  7. On the analysis of genome-wide association studies in family-based designs: a universal, robust analysis approach and an application to four genome-wide association studies.

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    Sungho Won

    2009-11-01

    Full Text Available For genome-wide association studies in family-based designs, we propose a new, universally applicable approach. The new test statistic exploits all available information about the association, while, by virtue of its design, it maintains the same robustness against population admixture as traditional family-based approaches that are based exclusively on the within-family information. The approach is suitable for the analysis of almost any trait type, e.g. binary, continuous, time-to-onset, multivariate, etc., and combinations of those. We use simulation studies to verify all theoretically derived properties of the approach, estimate its power, and compare it with other standard approaches. We illustrate the practical implications of the new analysis method by an application to a lung-function phenotype, forced expiratory volume in one second (FEV1 in 4 genome-wide association studies.

  8. Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE Cohorts

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    Unjin Shim

    2014-12-01

    Full Text Available Metabolic syndrome (MetS is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs, important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs, explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE was used for analysis, which include 8,842 individuals (age, 52.2 ± 8.9 years; body mass index, 24.6 ± 3.2 kg/m2. A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 × 10-6, and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 × 10-7, Bonferroni-adjusted p < 0.05. Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF, the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

  9. Meta-analysis of Genome-Wide Association Studies for Extraversion

    DEFF Research Database (Denmark)

    van den Berg, Stéphanie M; de Moor, Marleen H M; Verweij, K. J. H.

    2016-01-01

    small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found...... at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero...

  10. An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations.

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    Arunabha Majumdar

    2018-02-01

    Full Text Available Simultaneous analysis of genetic associations with multiple phenotypes may reveal shared genetic susceptibility across traits (pleiotropy. For a locus exhibiting overall pleiotropy, it is important to identify which specific traits underlie this association. We propose a Bayesian meta-analysis approach (termed CPBayes that uses summary-level data across multiple phenotypes to simultaneously measure the evidence of aggregate-level pleiotropic association and estimate an optimal subset of traits associated with the risk locus. This method uses a unified Bayesian statistical framework based on a spike and slab prior. CPBayes performs a fully Bayesian analysis by employing the Markov Chain Monte Carlo (MCMC technique Gibbs sampling. It takes into account heterogeneity in the size and direction of the genetic effects across traits. It can be applied to both cohort data and separate studies of multiple traits having overlapping or non-overlapping subjects. Simulations show that CPBayes can produce higher accuracy in the selection of associated traits underlying a pleiotropic signal than the subset-based meta-analysis ASSET. We used CPBayes to undertake a genome-wide pleiotropic association study of 22 traits in the large Kaiser GERA cohort and detected six independent pleiotropic loci associated with at least two phenotypes. This includes a locus at chromosomal region 1q24.2 which exhibits an association simultaneously with the risk of five different diseases: Dermatophytosis, Hemorrhoids, Iron Deficiency, Osteoporosis and Peripheral Vascular Disease. We provide an R-package 'CPBayes' implementing the proposed method.

  11. Association Between Coronary Artery Disease Genetic Variants and Subclinical Atherosclerosis: An Association Study and Meta-analysis.

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    Zabalza, Michel; Subirana, Isaac; Lluis-Ganella, Carla; Sayols-Baixeras, Sergi; de Groot, Eric; Arnold, Roman; Cenarro, Ana; Ramos, Rafel; Marrugat, Jaume; Elosua, Roberto

    2015-10-01

    Recent studies have identified several genetic variants associated with coronary artery disease. Some of these genetic variants are not associated with classical cardiovascular risk factors and the mechanism of such associations is unclear. The aim of the study was to determine whether these genetic variants are related to subclinical atherosclerosis measured by carotid intima media thickness, carotid stiffness, and ankle brachial index. A cross-sectional study nested in the follow-up of the REGICOR cohort was undertaken. The study included 2667 individuals. Subclinical atherosclerosis measurements were performed with standardized methods. Nine genetic variants were genotyped to assess associations with subclinical atherosclerosis, individually and in a weighted genetic risk score. A systematic review and meta-analysis of previous studies that analyzed these associations was undertaken. Neither the selected genetic variants nor the genetic risk score were significantly associated with subclinical atherosclerosis. In the meta-analysis, the rs1746048 (CXCL12; n = 10581) risk allele was directly associated with carotid intima-media thickness (β = 0.008; 95% confidence interval, 0.001-0.015), whereas the rs6725887 (WDR12; n = 7801) risk allele was inversely associated with this thickness (β = -0.013; 95% confidence interval, -0.024 to -0.003). The analyzed genetic variants seem to mediate their association with coronary artery disease through different mechanisms. Our results generate the hypothesis that the CXCL12 variant appears to influence coronary artery disease risk through arterial remodeling and thickening, whereas the WDR12 risk variant could be related to higher plaque vulnerability. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Analysis of Genome-Wide Association Studies with Multiple Outcomes Using Penalization

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    Liu, Jin; Huang, Jian; Ma, Shuangge

    2012-01-01

    Genome-wide association studies have been extensively conducted, searching for markers for biologically meaningful outcomes and phenotypes. Penalization methods have been adopted in the analysis of the joint effects of a large number of SNPs (single nucleotide polymorphisms) and marker identification. This study is partly motivated by the analysis of heterogeneous stock mice dataset, in which multiple correlated phenotypes and a large number of SNPs are available. Existing penalization methods designed to analyze a single response variable cannot accommodate the correlation among multiple response variables. With multiple response variables sharing the same set of markers, joint modeling is first employed to accommodate the correlation. The group Lasso approach is adopted to select markers associated with all the outcome variables. An efficient computational algorithm is developed. Simulation study and analysis of the heterogeneous stock mice dataset show that the proposed method can outperform existing penalization methods. PMID:23272092

  13. Pathway-based analysis of a melanoma genome-wide association study: analysis of genes related to tumour-immunosuppression.

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    Nils Schoof

    Full Text Available Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs in 43 genes (39 genomic regions related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (p(emp=0.002, as well as the subgroups related to the generation of tolerogenic dendritic cells (p(emp=0.006 and secretion of suppressive factors (p(emp=0.0004, thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.

  14. Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index

    DEFF Research Database (Denmark)

    Minster, Ryan L; Sanders, Jason L; Singh, Jatinder

    2015-01-01

    BACKGROUND: The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems. METHODS: We conducted a genome-wide association study and a genome-wide linkage analysis to map quantitative trait loci associated with the HAI and a modified HAI weighted...

  15. Improved score statistics for meta-analysis in single-variant and gene-level association studies.

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    Yang, Jingjing; Chen, Sai; Abecasis, Gonçalo

    2018-06-01

    Meta-analysis is now an essential tool for genetic association studies, allowing them to combine large studies and greatly accelerating the pace of genetic discovery. Although the standard meta-analysis methods perform equivalently as the more cumbersome joint analysis under ideal settings, they result in substantial power loss under unbalanced settings with various case-control ratios. Here, we investigate the power loss problem by the standard meta-analysis methods for unbalanced studies, and further propose novel meta-analysis methods performing equivalently to the joint analysis under both balanced and unbalanced settings. We derive improved meta-score-statistics that can accurately approximate the joint-score-statistics with combined individual-level data, for both linear and logistic regression models, with and without covariates. In addition, we propose a novel approach to adjust for population stratification by correcting for known population structures through minor allele frequencies. In the simulated gene-level association studies under unbalanced settings, our method recovered up to 85% power loss caused by the standard methods. We further showed the power gain of our methods in gene-level tests with 26 unbalanced studies of age-related macular degeneration . In addition, we took the meta-analysis of three unbalanced studies of type 2 diabetes as an example to discuss the challenges of meta-analyzing multi-ethnic samples. In summary, our improved meta-score-statistics with corrections for population stratification can be used to construct both single-variant and gene-level association studies, providing a useful framework for ensuring well-powered, convenient, cross-study analyses. © 2018 WILEY PERIODICALS, INC.

  16. Imputation-based analysis of association studies: candidate regions and quantitative traits.

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    Bertrand Servin

    2007-07-01

    Full Text Available We introduce a new framework for the analysis of association studies, designed to allow untyped variants to be more effectively and directly tested for association with a phenotype. The idea is to combine knowledge on patterns of correlation among SNPs (e.g., from the International HapMap project or resequencing data in a candidate region of interest with genotype data at tag SNPs collected on a phenotyped study sample, to estimate ("impute" unmeasured genotypes, and then assess association between the phenotype and these estimated genotypes. Compared with standard single-SNP tests, this approach results in increased power to detect association, even in cases in which the causal variant is typed, with the greatest gain occurring when multiple causal variants are present. It also provides more interpretable explanations for observed associations, including assessing, for each SNP, the strength of the evidence that it (rather than another correlated SNP is causal. Although we focus on association studies with quantitative phenotype and a relatively restricted region (e.g., a candidate gene, the framework is applicable and computationally practical for whole genome association studies. Methods described here are implemented in a software package, Bim-Bam, available from the Stephens Lab website http://stephenslab.uchicago.edu/software.html.

  17. Association between Herpesviruses and Chronic Periodontitis: A Meta-Analysis Based on Case-Control Studies.

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    Zhu, Ce; Li, Fei; Wong, May Chun Mei; Feng, Xi-Ping; Lu, Hai-Xia; Xu, Wei

    2015-01-01

    Numerous studies have investigated the associations between herpesviruses and chronic periodontitis; however, the results remain controversial. To derive a more precise estimation, a meta-analysis on all available studies was performed to identify the association between herpesviruses and chronic periodontitis. A computerized literature search was conducted in December 2014 to identify eligible case-control studies from the PUBMED and EMBASE databases according to inclusion and exclusion criteria. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess the association between herpesviruses and risk of chronic periodontitis. A fixed or random effects model was determined based on a heterogeneity test. Sensitivity analysis was conducted to investigate stability and reliability. Publication bias was investigated using the Begg rank correlation test and Egger's funnel plot. Ten eligible studies were included to investigate the association between Epstein-Barr virus (EBV) and chronic periodontitis. The results showed that EBV has a significant association with chronic periodontitis compared with periodontally healthy group (OR = 5.74, 95% CI = 2.53-13.00, Pchronic periodontitis was analyzed in 10 studies. The pooled result showed that HCMV also has a significant association with chronic periodontitis (OR = 3.59, 95% CI = 1.41-9.16, P = 0.007). Similar results were found in the sensitivity analyses. No significant publication bias was observed. Two eligible studies were included to investigate the association between herpes simplex virus (HSV) and chronic periodontitis risk. The association between HSV and chronic periodontitis was inconclusive (OR = 2.81 95% CI = 0.95-8.27, P = 0.06). Only one included study investigated the association between human herpesvirus 7 (HHV-7) and chronic periodontitis risk (OR = 1.00, 95% CI = 0.21-4.86). The findings of this meta-analysis suggest that two members of the herpesvirus family, EBV

  18. MetaSeq: privacy preserving meta-analysis of sequencing-based association studies.

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    Singh, Angad Pal; Zafer, Samreen; Pe'er, Itsik

    2013-01-01

    Human genetics recently transitioned from GWAS to studies based on NGS data. For GWAS, small effects dictated large sample sizes, typically made possible through meta-analysis by exchanging summary statistics across consortia. NGS studies groupwise-test for association of multiple potentially-causal alleles along each gene. They are subject to similar power constraints and therefore likely to resort to meta-analysis as well. The problem arises when considering privacy of the genetic information during the data-exchange process. Many scoring schemes for NGS association rely on the frequency of each variant thus requiring the exchange of identity of the sequenced variant. As such variants are often rare, potentially revealing the identity of their carriers and jeopardizing privacy. We have thus developed MetaSeq, a protocol for meta-analysis of genome-wide sequencing data by multiple collaborating parties, scoring association for rare variants pooled per gene across all parties. We tackle the challenge of tallying frequency counts of rare, sequenced alleles, for metaanalysis of sequencing data without disclosing the allele identity and counts, thereby protecting sample identity. This apparent paradoxical exchange of information is achieved through cryptographic means. The key idea is that parties encrypt identity of genes and variants. When they transfer information about frequency counts in cases and controls, the exchanged data does not convey the identity of a mutation and therefore does not expose carrier identity. The exchange relies on a 3rd party, trusted to follow the protocol although not trusted to learn about the raw data. We show applicability of this method to publicly available exome-sequencing data from multiple studies, simulating phenotypic information for powerful meta-analysis. The MetaSeq software is publicly available as open source.

  19. metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis.

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    Cichonska, Anna; Rousu, Juho; Marttinen, Pekka; Kangas, Antti J; Soininen, Pasi; Lehtimäki, Terho; Raitakari, Olli T; Järvelin, Marjo-Riitta; Salomaa, Veikko; Ala-Korpela, Mika; Ripatti, Samuli; Pirinen, Matti

    2016-07-01

    A dominant approach to genetic association studies is to perform univariate tests between genotype-phenotype pairs. However, analyzing related traits together increases statistical power, and certain complex associations become detectable only when several variants are tested jointly. Currently, modest sample sizes of individual cohorts, and restricted availability of individual-level genotype-phenotype data across the cohorts limit conducting multivariate tests. We introduce metaCCA, a computational framework for summary statistics-based analysis of a single or multiple studies that allows multivariate representation of both genotype and phenotype. It extends the statistical technique of canonical correlation analysis to the setting where original individual-level records are not available, and employs a covariance shrinkage algorithm to achieve robustness.Multivariate meta-analysis of two Finnish studies of nuclear magnetic resonance metabolomics by metaCCA, using standard univariate output from the program SNPTEST, shows an excellent agreement with the pooled individual-level analysis of original data. Motivated by strong multivariate signals in the lipid genes tested, we envision that multivariate association testing using metaCCA has a great potential to provide novel insights from already published summary statistics from high-throughput phenotyping technologies. Code is available at https://github.com/aalto-ics-kepaco anna.cichonska@helsinki.fi or matti.pirinen@helsinki.fi Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  20. Evolutionary Meta-Analysis of Association Studies Reveals Ancient Constraints Affecting Disease Marker Discovery

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    Dudley, Joel T.; Chen, Rong; Sanderford, Maxwell; Butte, Atul J.; Kumar, Sudhir

    2012-01-01

    Genome-wide disease association studies contrast genetic variation between disease cohorts and healthy populations to discover single nucleotide polymorphisms (SNPs) and other genetic markers revealing underlying genetic architectures of human diseases. Despite scores of efforts over the past decade, many reproducible genetic variants that explain substantial proportions of the heritable risk of common human diseases remain undiscovered. We have conducted a multispecies genomic analysis of 5,831 putative human risk variants for more than 230 disease phenotypes reported in 2,021 studies. We find that the current approaches show a propensity for discovering disease-associated SNPs (dSNPs) at conserved genomic positions because the effect size (odds ratio) and allelic P value of genetic association of an SNP relates strongly to the evolutionary conservation of their genomic position. We propose a new measure for ranking SNPs that integrates evolutionary conservation scores and the P value (E-rank). Using published data from a large case-control study, we demonstrate that E-rank method prioritizes SNPs with a greater likelihood of bona fide and reproducible genetic disease associations, many of which may explain greater proportions of genetic variance. Therefore, long-term evolutionary histories of genomic positions offer key practical utility in reassessing data from existing disease association studies, and in the design and analysis of future studies aimed at revealing the genetic basis of common human diseases. PMID:22389448

  1. Is sarcopenia associated with depression? A systematic review and meta-analysis of observational studies.

    Science.gov (United States)

    Chang, Ke-Vin; Hsu, Tsai-Hsuan; Wu, Wei-Ting; Huang, Kuo-Chin; Han, Der-Sheng

    2017-09-01

    to explore whether sarcopenia is associated with depression. electronic literature databases from PubMed, Scopus, Embase and Google Scholar were searched. A systematic review and meta-analysis of observational studies was conducted. community and outpatient clinic. people with and without diagnoses of sarcopenia. outcome measures of depression. about 15 articles were included, 5 of which were retrieved for narrative review. The crude odds ratios (ORs) between sarcopenia and depression were extracted from the remaining 10 studies, 6 of which also included adjusted ORs. Sarcopenia was associated with depression without adjusting covariates (crude OR, 1.640; 95% confidence interval (CI), 1.247-2.155). After adjusting for potential confounders such as age, gender, cognitive performance and physical activity, sarcopenia still demonstrated a significant positive association with depression (adjusted OR, 1.821; 95% CI, 1.160-2.859). A stratified analysis showed that the studies that used bioelectrical impedance analysis for measurement of body composition tended to have an elevated association between sarcopenia and depression compared with those that used dual-energy X-ray absorptiometry or equation estimation. sarcopenia was independently associated with depression. The causal relationship between the two clinical conditions requires future validation with cohort studies. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

  2. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

    DEFF Research Database (Denmark)

    Zillikens, M Carola; Demissie, Serkalem; Hsu, Yi-Hsiang

    2017-01-01

    Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorpt...... a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.......-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p 

  3. Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes

    KAUST Repository

    Chatterjee, Nilanjan; Chen, Yi-Hau; Luo, Sheng; Carroll, Raymond J.

    2009-01-01

    Although prospective logistic regression is the standard method of analysis for case-control data, it has been recently noted that in genetic epidemiologic studies one can use the "retrospective" likelihood to gain major power by incorporating various population genetics model assumptions such as Hardy-Weinberg-Equilibrium (HWE), gene-gene and gene-environment independence. In this article we review these modern methods and contrast them with the more classical approaches through two types of applications (i) association tests for typed and untyped single nucleotide polymorphisms (SNPs) and (ii) estimation of haplotype effects and haplotype-environment interactions in the presence of haplotype-phase ambiguity. We provide novel insights to existing methods by construction of various score-tests and pseudo-likelihoods. In addition, we describe a novel two-stage method for analysis of untyped SNPs that can use any flexible external algorithm for genotype imputation followed by a powerful association test based on the retrospective likelihood. We illustrate applications of the methods using simulated and real data. © Institute of Mathematical Statistics, 2009.

  4. Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes

    KAUST Repository

    Chatterjee, Nilanjan

    2009-11-01

    Although prospective logistic regression is the standard method of analysis for case-control data, it has been recently noted that in genetic epidemiologic studies one can use the "retrospective" likelihood to gain major power by incorporating various population genetics model assumptions such as Hardy-Weinberg-Equilibrium (HWE), gene-gene and gene-environment independence. In this article we review these modern methods and contrast them with the more classical approaches through two types of applications (i) association tests for typed and untyped single nucleotide polymorphisms (SNPs) and (ii) estimation of haplotype effects and haplotype-environment interactions in the presence of haplotype-phase ambiguity. We provide novel insights to existing methods by construction of various score-tests and pseudo-likelihoods. In addition, we describe a novel two-stage method for analysis of untyped SNPs that can use any flexible external algorithm for genotype imputation followed by a powerful association test based on the retrospective likelihood. We illustrate applications of the methods using simulated and real data. © Institute of Mathematical Statistics, 2009.

  5. Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis.

    Science.gov (United States)

    Alg, Varinder S; Ke, Xiayi; Grieve, Joan; Bonner, Stephen; Walsh, Daniel C; Bulters, Diederik; Kitchen, Neil; Houlden, Henry; Werring, David J

    2018-01-15

    Abnormalities in Matrix Metalloproteinase (MMP) genes, which are important in extracellular matrix (ECM) maintenance and therefore arterial wall integrity are a plausible underlying mechanism of intracranial aneurysm (IA) formation, growth and subsequent rupture. We investigated whether the rs243865 C > T SNP (single nucleotide polymorphism) within the MMP-2 gene (which influences gene transcription) is associated with IA compared to matched controls. We conducted a case-control genetic association study, adjusted for known IA risk factors (smoking and hypertension), in a UK Caucasian population of 1409 patients with intracranial aneurysms (IA), and 1290 matched controls, to determine the association of the rs243865 C > T functional MMP-2 gene SNP with IA (overall, and classified as ruptured and unruptured). We also undertook a meta-analysis of two previous studies examining this SNP. The rs243865 T allele was associated with IA presence in univariate (OR 1.18 [95% CI 1.04-1.33], p = .01) and in multi-variable analyses adjusted for smoking and hypertension status (OR 1.16 [95% CI 1.01-1.35], p = .042). Subgroup analysis demonstrated an association of the rs243865 SNP with ruptured IA (OR 1.18 [95% CI 1.03-1.34] p = .017), but, not unruptured IA (OR 1.17 [95% CI 0.97-1.42], p = .11). Our study demonstrated an association between the functional MMP-2 rs243865 variant and IAs. Our findings suggest a genetic role for altered extracellular matrix integrity in the pathogenesis of IA development and rupture.

  6. SNP-based pathway enrichment analysis for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Potkin Steven G

    2011-04-01

    Full Text Available Abstract Background Recently we have witnessed a surge of interest in using genome-wide association studies (GWAS to discover the genetic basis of complex diseases. Many genetic variations, mostly in the form of single nucleotide polymorphisms (SNPs, have been identified in a wide spectrum of diseases, including diabetes, cancer, and psychiatric diseases. A common theme arising from these studies is that the genetic variations discovered by GWAS can only explain a small fraction of the genetic risks associated with the complex diseases. New strategies and statistical approaches are needed to address this lack of explanation. One such approach is the pathway analysis, which considers the genetic variations underlying a biological pathway, rather than separately as in the traditional GWAS studies. A critical challenge in the pathway analysis is how to combine evidences of association over multiple SNPs within a gene and multiple genes within a pathway. Most current methods choose the most significant SNP from each gene as a representative, ignoring the joint action of multiple SNPs within a gene. This approach leads to preferential identification of genes with a greater number of SNPs. Results We describe a SNP-based pathway enrichment method for GWAS studies. The method consists of the following two main steps: 1 for a given pathway, using an adaptive truncated product statistic to identify all representative (potentially more than one SNPs of each gene, calculating the average number of representative SNPs for the genes, then re-selecting the representative SNPs of genes in the pathway based on this number; and 2 ranking all selected SNPs by the significance of their statistical association with a trait of interest, and testing if the set of SNPs from a particular pathway is significantly enriched with high ranks using a weighted Kolmogorov-Smirnov test. We applied our method to two large genetically distinct GWAS data sets of schizophrenia, one

  7. Statistical testing and power analysis for brain-wide association study.

    Science.gov (United States)

    Gong, Weikang; Wan, Lin; Lu, Wenlian; Ma, Liang; Cheng, Fan; Cheng, Wei; Grünewald, Stefan; Feng, Jianfeng

    2018-04-05

    The identification of connexel-wise associations, which involves examining functional connectivities between pairwise voxels across the whole brain, is both statistically and computationally challenging. Although such a connexel-wise methodology has recently been adopted by brain-wide association studies (BWAS) to identify connectivity changes in several mental disorders, such as schizophrenia, autism and depression, the multiple correction and power analysis methods designed specifically for connexel-wise analysis are still lacking. Therefore, we herein report the development of a rigorous statistical framework for connexel-wise significance testing based on the Gaussian random field theory. It includes controlling the family-wise error rate (FWER) of multiple hypothesis testings using topological inference methods, and calculating power and sample size for a connexel-wise study. Our theoretical framework can control the false-positive rate accurately, as validated empirically using two resting-state fMRI datasets. Compared with Bonferroni correction and false discovery rate (FDR), it can reduce false-positive rate and increase statistical power by appropriately utilizing the spatial information of fMRI data. Importantly, our method bypasses the need of non-parametric permutation to correct for multiple comparison, thus, it can efficiently tackle large datasets with high resolution fMRI images. The utility of our method is shown in a case-control study. Our approach can identify altered functional connectivities in a major depression disorder dataset, whereas existing methods fail. A software package is available at https://github.com/weikanggong/BWAS. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Berndt, Sonja I; Camp, Nicola J; Skibola, Christine F; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S; Smedby, Karin E; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S; Lan, Qing; Teras, Lauren R; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R; Hartge, Patricia; Purdue, Mark P; Birmann, Brenda M; Vajdic, Claire M; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G; Shanafelt, Tait D; Novak, Anne J; Kay, Neil E; Liebow, Mark; Cunningham, Julie M; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A; Diver, W Ryan; Link, Brian K; Weiner, George J; Conde, Lucia; Bracci, Paige M; Riby, Jacques; Arnett, Donna K; Zhi, Degui; Leach, Justin M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G; Achenbach, Sara J; Vachon, Celine M; Goldin, Lynn R; Strom, Sara S; Leis, Jose F; Weinberg, J Brice; Caporaso, Neil E; Norman, Aaron D; De Roos, Anneclaire J; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María-Dolores; Vermeulen, Roel C H|info:eu-repo/dai/nl/216532620; Travis, Ruth C; Southey, Melissa C; Milne, Roger L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R; Villano, Danylo J; Maria, Ann; Spinelli, John J; Gascoyne, Randy D; Connors, Joseph M; Bertrand, Kimberly A; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E; Snowden, John A; Wright, Josh; Fraumeni, Joseph F; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R; Chanock, Stephen J; Rothman, Nathaniel; Slager, Susan L

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and

  9. Association between type 1 diabetes mellitus and risk of epilepsy: A meta-analysis of observational studies.

    Science.gov (United States)

    Yan, Dandan; Zhao, Enfa; Zhang, Hong; Luo, Xiaohui; Du, Yajuan

    2017-01-01

    A potential association between type 1 diabetes mellitus and subsequent epilepsy emerged in recent studies. This study aimed to evaluate the possible relationship between type 1 diabetes mellitus and epilepsy using meta-analysis. Pubmed, ISI Web of Knowledge, Embase and Cochrane Library were searched for potential studies of the association between type 1 diabetes mellitus and epilepsy from inception to February 1, 2017. Two investigators independently screened studies for inclusion and extracted related data; discrepancies were solved by consensus. Random effects model of Hazard Ratio (HR) was used to estimate the strength of association. We identified 13 papers from potentially relevant articles of which 3 cohort studies met the inclusion criteria. Random effects meta-analysis showed that type 1 diabetes mellitus was associated with an increased risk of epilepsy with HR = 3.29 (95% CI: 2.61-4.14; I 2 = 0, p = 0.689). Similar results were observed in type 1 diabetes mellitus patents younger than 18-years-old with HR = 2.96 (95% CI: 2.28-3.84; I 2 = 0, p = 0.571). Meta-analysis of 2 studies that adjusted for potential confounders yielded an increased risk of epilepsy with HR = 2.89 (95% CI: 2.26-3.70; I 2 = 0, p = 0.831). The meta-analysis indicates that type 1 diabetes mellitus is associated with a statistically significant increased risk for epilepsy compared to those without type 1 diabetes mellitus.

  10. Network Graph Analysis of Gene-Gene Interactions in Genome-Wide Association Study Data

    Directory of Open Access Journals (Sweden)

    Sungyoung Lee

    2012-12-01

    Full Text Available Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs. For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR is one of the powerful and efficient methods for detecting high-order gene-gene (GxG interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI. Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

  11. Network graph analysis of gene-gene interactions in genome-wide association study data.

    Science.gov (United States)

    Lee, Sungyoung; Kwon, Min-Seok; Park, Taesung

    2012-12-01

    Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs). For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR) is one of the powerful and efficient methods for detecting high-order gene-gene (GxG) interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE) data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI). Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

  12. GWAMA: software for genome-wide association meta-analysis

    Directory of Open Access Journals (Sweden)

    Mägi Reedik

    2010-05-01

    Full Text Available Abstract Background Despite the recent success of genome-wide association studies in identifying novel loci contributing effects to complex human traits, such as type 2 diabetes and obesity, much of the genetic component of variation in these phenotypes remains unexplained. One way to improving power to detect further novel loci is through meta-analysis of studies from the same population, increasing the sample size over any individual study. Although statistical software analysis packages incorporate routines for meta-analysis, they are ill equipped to meet the challenges of the scale and complexity of data generated in genome-wide association studies. Results We have developed flexible, open-source software for the meta-analysis of genome-wide association studies. The software incorporates a variety of error trapping facilities, and provides a range of meta-analysis summary statistics. The software is distributed with scripts that allow simple formatting of files containing the results of each association study and generate graphical summaries of genome-wide meta-analysis results. Conclusions The GWAMA (Genome-Wide Association Meta-Analysis software has been developed to perform meta-analysis of summary statistics generated from genome-wide association studies of dichotomous phenotypes or quantitative traits. Software with source files, documentation and example data files are freely available online at http://www.well.ox.ac.uk/GWAMA.

  13. Bias due to two-stage residual-outcome regression analysis in genetic association studies.

    Science.gov (United States)

    Demissie, Serkalem; Cupples, L Adrienne

    2011-11-01

    Association studies of risk factors and complex diseases require careful assessment of potential confounding factors. Two-stage regression analysis, sometimes referred to as residual- or adjusted-outcome analysis, has been increasingly used in association studies of single nucleotide polymorphisms (SNPs) and quantitative traits. In this analysis, first, a residual-outcome is calculated from a regression of the outcome variable on covariates and then the relationship between the adjusted-outcome and the SNP is evaluated by a simple linear regression of the adjusted-outcome on the SNP. In this article, we examine the performance of this two-stage analysis as compared with multiple linear regression (MLR) analysis. Our findings show that when a SNP and a covariate are correlated, the two-stage approach results in biased genotypic effect and loss of power. Bias is always toward the null and increases with the squared-correlation between the SNP and the covariate (). For example, for , 0.1, and 0.5, two-stage analysis results in, respectively, 0, 10, and 50% attenuation in the SNP effect. As expected, MLR was always unbiased. Since individual SNPs often show little or no correlation with covariates, a two-stage analysis is expected to perform as well as MLR in many genetic studies; however, it produces considerably different results from MLR and may lead to incorrect conclusions when independent variables are highly correlated. While a useful alternative to MLR under , the two -stage approach has serious limitations. Its use as a simple substitute for MLR should be avoided. © 2011 Wiley Periodicals, Inc.

  14. Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts.

    Directory of Open Access Journals (Sweden)

    Vesna Boraska

    Full Text Available Brachial circumference (BC, also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05 in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.

  15. Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology

    OpenAIRE

    Springelkamp, Henriët; Mishra, Aniket; Hysi, Pirro G.; Gharahkhani, Puya; Höhn, René; Khor, Chiea-Chuen; Cooke Bailey, Jessica N.; Luo, Xiaoyan; Ramdas, Wishal D.; Vithana, Eranga; Koh, Victor; Yazar, Seyhan; Xu, Liang; Forward, Hannah; Kearns, Lisa S.

    2015-01-01

    Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asia...

  16. Elevated alanine aminotransferase is strongly associated with incident metabolic syndrome: a meta-analysis of prospective studies.

    Directory of Open Access Journals (Sweden)

    Zhengtao Liu

    Full Text Available BACKGROUND: The incidence of metabolic syndrome (MetS is rapidly increasing worldwide and associated with alanine aminotransferase (ALT activity. However, the impact of ALT activity on MetS incidence is inconsistent in published literature. We therefore estimated the association between elevated ALT activity and incident MetS through a meta-analysis of prospective cohort studies. METHODS/PRINCIPAL FINDINGS: All published prospective cohort studies on the association between elevated ALT activity and incident MetS were retrieved from Pubmed, Embase, and the Institute for Scientific Information (ISI. In all, seven prospective cohort studies, with 31545 participants and 2873 cases of incident MetS were recruited. If there was insignificant heterogeneity (P-value>0.05 and I(2<50%, the fixed-effect model was used to calculate the pooled relative risks (RRs of incident MetS induced by raised ALT. Otherwise, the random-effect model was used. The calculated RR was 1.81 (95% confidence interval [CI]: 1.49-2.14 when the incidence of MetS was compared between the highest versus the lowest classification of ALT activities. The pooled RR was 1.13 (95% CI: 1.11-1.16 in dose-response analysis with 5 units per liter (U/l of ALT increment. Subgroup analysis suggested that gender disparity might be the main origin of heterogeneity in overall analysis (P = 0.007 between RRs of gender-specific subgroups evaluated with 5 U/l increments of ALT. Women had a higher dose-response risk of MetS incidence (1.38, 95% CI: 1.20-1.55 than men. Furthermore, sensitivity analysis confirmed the stability of results. No publication bias was found in our meta-analysis. CONCLUSIONS/SIGNIFICANCE: Current evidence from prospective studies supports the association between ALT elevation and increasing MetS incidence. This association is closer and more consistent in female population. Further studies are needed to confirm this association and to investigate the potential mechanism of

  17. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

    DEFF Research Database (Denmark)

    Wang, Zhaoming; McGlynn, Katherine A.; Rajpert-De Meyts, Ewa

    2017-01-01

    The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the fi...

  18. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study.

    Directory of Open Access Journals (Sweden)

    Jibin Liu

    Full Text Available Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM risk.Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015. Study-specific risk estimates were pooled under the random-effects model.Two case-control studies (846 MM patients and 843 controls and five cohort studies (including 844,246 participants and 5,737 MM cases were identified. For caffeinated coffee, the pooled relative risk (RR of MM was 0.81 [95% confidential interval (95% CI = 0.68-0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912-0.999 for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326. Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81-1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake.This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings.

  19. A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

    DEFF Research Database (Denmark)

    Amin Al Olama, Ali; Kote-Jarai, Zsofia; Schumacher, Fredrick R

    2013-01-01

    Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS inc...

  20. A systematic analysis of the association studies between CASP8 ...

    Indian Academy of Sciences (India)

    precision medicine or health. Keywords: Breast cancer; CASP8; rs1045485 polymorphism; meta-analysis. Introduction. CASP8 ... peptidase that can activate various cellular proteases or proteins, leading to apoptosis through the .... While meta-analysis shed light on the trend of association between SNP and disease risk,.

  1. A meta-analysis of genome-wide association studies of follicular lymphoma

    Directory of Open Access Journals (Sweden)

    Skibola Christine F

    2012-10-01

    Full Text Available Abstract Background B-cell non-Hodgkin lymphoma represents a diverse group of hematological malignancies, of which follicular lymphoma (FL is one of the most common subtypes. Family and epidemiological studies suggest an important genetic role in the etiology of FL. In recent genome-wide association studies (GWAS of FL, several genetic susceptibility loci have been identified on chromosome 6p21.33 (rs6457327 and 6p21.32 (rs10484561, rs2647012 in the human leukocyte antigen class I and class II regions. To identify new genetic variants and further elucidate the genetic basis of FL, a meta-analysis was performed of the top 1000 SNPs associated with FL risk from two GWAS in the US, Denmark and Sweden (592 cases, 1541 controls, with independent validation in 107 cases and 681 controls. Results rs9275517 and rs3117222 in the HLA class II region were validated and inversely associated with FL risk (rs9275517: OR = 0.63, 95% CI = 0.55-0.73, p = 4.03 × 10-11; rs3117222: OR = 0.66, 95% CI = 0.57-0.77, p = 1.45 × 10-7. rs9275517, which is in high linkage disequilibrium with rs2647012 (r2 = 0.9, was no longer associated with FL after conditioning on rs2647012. The rs3117222 association was independent of established FL SNPs, but not of the HLA-DPB1*0301 allele. Using publicly available gene expression profiles with matching genotype information, we found that rs3117222 also was significantly correlated with increased HLA-DPB1 expression. Conclusions By performing a meta-analysis of two GWAS of FL, we further validated the relevance of HLA-DPB1*0301 as a protective allele in the pathogenesis of FL. Moreover, the protective rs3117222 A allele correlated with increased levels of HLA-DPB1, suggesting a possible disease mechanism involving HLA-DPB1 expression regulation. Our results add further support to the major role of HLA genetic variation in the pathogenesis of FL.

  2. Association between smoking and the risk of acute mountain sickness: a meta-analysis of observational studies.

    Science.gov (United States)

    Xu, Chen; Lu, Hong-Xiang; Wang, Yu-Xiao; Chen, Yu; Yang, Sheng-Hong; Luo, Yong-Jun

    2016-01-01

    People rapidly ascending to high altitudes (>2500 m) may suffer from acute mountain sickness (AMS). The association between smoking and AMS risk remains unclear. Therefore, we performed a meta-analysis to evaluate the association between smoking and AMS risk. The association between smoking and AMS risk was determined according to predefined criteria established by our team. Meta-analysis was conducted according to the PRISMA guidelines. We included all relevant studies listed in the PubMed and Embase databases as of September 2015 in this meta-analysis and performed systemic searches using the terms "smoking", "acute mountain sickness" and "risk factor". The included studies were required to provide clear explanations regarding their definitions of smoking, the final altitudes reached by their participants and the diagnostic criteria used to diagnose AMS. Odds ratios ( ORs ) were used to evaluate the association between smoking and AMS risk across the studies, and the Q statistic was used to test OR heterogeneity, which was considered significant when P  smoking patients and 1986 non-smoking controls to analyze the association between smoking and AMS risk. We observed a significant association between AMS and smoking ( OR  = 0.71, 95% CI 0.52-0.96, P  = 0.03). We determined that smoking may protect against AMS development. However, we do not advise smoking to prevent AMS. More studies are necessary to confirm the role of smoking in AMS risk.

  3. Association between exposure to noise and risk of hypertension: a meta-analysis of observational epidemiological studies.

    Science.gov (United States)

    Fu, Wenning; Wang, Chao; Zou, Li; Liu, Qiaoyan; Gan, Yong; Yan, Shijiao; Song, Fujian; Wang, Zhihong; Lu, Zuxun; Cao, Shiyi

    2017-12-01

    An increasing amount of original studies suggested that exposure to noise could be associated with the risk of hypertension, but the results remain inconsistent and inconclusive. We aimed to synthesize available epidemiological evidence about the relationship between various types of noise and hypertension, and to explore the potential dose-response relationship between them in an up-to-date meta-analysis. We conducted a literature search of PubMed and Embase from these databases' inception through December 2016 to identify observational epidemiological studies examining the association between noise and risk of hypertension. A random effects model was used to combine the results of included studies. Dose-response meta-analysis was conducted to examine the potential dose-response relationship. In total, 32 studies (five cohort studies, one case-control study, and 26 cross-section studies) involving 264 678 participants were eligible for inclusion. Pooled result showed that living or working in environment with noise exposure was significantly associated with increased risk of hypertension (odds ratio 1.62; 95% confidence interval: 1.40-1.88). We found no evidence of a curve linear association between noise and risk of hypertension. A dose-response analysis suggested that, for an increment of per 10 dB(A) of noise, the combined odds ratio of hypertension was 1.06 (95% confidence interval: 1.04-1.08). Integrated epidemiological evidence supports the hypothesis that exposure to noise may be a risk factor of hypertension, and there is a positive dose-response association between them.

  4. Rare variant association analysis in case-parents studies by allowing for missing parental genotypes.

    Science.gov (United States)

    Li, Yumei; Xiang, Yang; Xu, Chao; Shen, Hui; Deng, Hongwen

    2018-01-15

    The development of next-generation sequencing technologies has facilitated the identification of rare variants. Family-based design is commonly used to effectively control for population admixture and substructure, which is more prominent for rare variants. Case-parents studies, as typical strategies in family-based design, are widely used in rare variant-disease association analysis. Current methods in case-parents studies are based on complete case-parents data; however, parental genotypes may be missing in case-parents trios, and removing these data may lead to a loss in statistical power. The present study focuses on testing for rare variant-disease association in case-parents study by allowing for missing parental genotypes. In this report, we extended the collapsing method for rare variant association analysis in case-parents studies to allow for missing parental genotypes, and investigated the performance of two methods by using the difference of genotypes between affected offspring and their corresponding "complements" in case-parent trios and TDT framework. Using simulations, we showed that, compared with the methods just only using complete case-parents data, the proposed strategy allowing for missing parental genotypes, or even adding unrelated affected individuals, can greatly improve the statistical power and meanwhile is not affected by population stratification. We conclude that adding case-parents data with missing parental genotypes to complete case-parents data set can greatly improve the power of our strategy for rare variant-disease association.

  5. Association of sedentary behaviour with colon and rectal cancer: a meta-analysis of observational studies.

    Science.gov (United States)

    Cong, Y J; Gan, Y; Sun, H L; Deng, J; Cao, S Y; Xu, X; Lu, Z X

    2014-02-04

    Sedentary behaviour is ubiquitous in modern society. Emerging studies have focused on the health consequences of sedentary behaviour, including colorectal cancer, but whether sedentary behaviour is associated with the risks of colon and rectal cancer remains unclear. No systematic reviews have applied quantitative techniques to independently compute summary risk estimates. We aimed to conduct a meta-analysis to investigate this issue. We searched PubMed, Embase, and Google Scholar databases up to May 2013 to identify cohort and case-control studies that evaluated the association between sedentary behaviour and colon or rectal cancer. A random-effect model was used to pool the results of included studies. Publication bias was assessed by using Begg's funnel plot. Twenty-three studies with 63 reports were included in our meta-analysis. These groups included 4,324,462 participants (27,231 colon cancer cases and 13,813 rectal cancer cases). Sedentary behaviour was significantly associated with colon cancer (relative risk (RR): 1.30, 95% confidence interval (CI): 1.22-1.39) but did not have a statistically significant association with rectal cancer (RR 1.05, 95% CI, 0.98-1.13). Subgroup analyses suggested that the odds ratio (OR) of colon cancer was 1.46 (95% CI: 1.22-1.68) in the case-control studies, and the RR was 1.27 (95% CI: 1.18-1.36) in the cohort studies, the OR of rectal cancer was 1.06 (95% CI: 0.85-1.33) in the case-control studies, and the RR was 1.06 (95% CI, 1.01-1.12) in the cohort studies. Sedentary behaviour is associated with an increased risk of colon cancer. Subgroup analyses suggest a positive association between sedentary behaviour and risk of rectal cancer in cohort studies. Reducing sedentary behaviour is potentially important for the prevention of colorectal cancer.

  6. Excess mortality associated with hypopituitarism in adults: a meta-analysis of observational studies.

    Science.gov (United States)

    Pappachan, Joseph M; Raskauskiene, Diana; Kutty, V Raman; Clayton, Richard N

    2015-04-01

    Several previous observational studies showed an association between hypopituitarism and excess mortality. Reports on reduction of standard mortality ratio (SMR) with GH replacement have been published recently. This meta-analysis assessed studies reporting SMR to clarify mortality risk in hypopituitary adults and also the potential benefit conferred by GH replacement. A literature search was performed in Medline, Embase, and Cochrane library up to March 31, 2014. Studies with or without GH replacement reporting SMR with 95% confidence intervals (95% CI) were included. Patient characteristics, SMR data, and treatment outcomes were independently assessed by two authors, and with consensus from third author, studies were selected for analysis. Meta-analysis was performed in all studies together, and those without and with GH replacement separately, using the statistical package metafor in R. Six studies reporting a total of 19 153 hypopituiatary adults with a follow-up duration of more than 99,000 person years were analyzed. Hypopituitarism was associated with an overall excess mortality (weighted SMR, 1.99; 95% CI, 1.21-2.76) in adults. Female hypopituitary adults showed higher SMR compared with males (2.53 vs 1.71). Onset of hypopituitarism at a younger age was associated with higher SMR. GH replacement improved the mortality risk in hypopituitary adults that is comparable to the background population (SMR with GH replacement, 1.15; 95% CI, 1.05-1.24 vs SMR without GH, 2.40; 95% CI, 1.46-3.34). GH replacement conferred lower mortality benefit in hypopituitary women compared with men (SMR, 1.57; 95% CI, 1.38-1.77 vs 0.95; 95% CI, 0.85-1.06). There was a potential selection bias of benefit of GH replacement from a post-marketing data necessitating further evidence from long-term randomized controlled trials. Hypopituitarism may increase premature mortality in adults. Mortality benefit from GH replacement in hypopituitarism is less pronounced in women than men.

  7. Is meat consumption associated with depression? A meta-analysis of observational studies.

    Science.gov (United States)

    Zhang, Yi; Yang, Ye; Xie, Ming-Sheng; Ding, Xiang; Li, Hui; Liu, Zhi-Chen; Peng, Shi-Fang

    2017-12-28

    A number of epidemiological studies have examined the effect of meat consumption on depression. However, no conclusion has been reached. The aim of this study was to examine the relationship between meat consumption and depression. The electronic databases of PUBMED and EMBASE were searched up to March 2017, for observational studies that examined the relationship between meat consumption and depression. The pooled odds ratio (OR) for the prevalence of depression and the relative risk (RR) for the incidence of depression, as well as their corresponding 95% confidence interval (CI), were calculated respectively (the highest versus the lowest category of meat consumption). A total of eight observational studies (three cross-sectional, three cohort and two case-control studies) were included in this meta-analysis. Specifically, six studies were related to the prevalence of depression, and the overall multi-variable adjusted OR suggested no significant association between meat consumption and the prevalence of depression (OR = 0.89, 95% CI: 0.65 to 1.22; P = 0.469). In contrast, for the three studies related to the incidence of depression, the overall multi-variable adjusted RR evidenced an association between meat consumption and a moderately higher incidence of depression (RR = 1.13, 95% CI: 1.03 to 1.24; P = 0.013). Meat consumption may be associated with a moderately higher risk of depression. However, it still warrants further studies to confirm such findings due to the limited number of prospective studies.

  8. SQC: secure quality control for meta-analysis of genome-wide association studies.

    Science.gov (United States)

    Huang, Zhicong; Lin, Huang; Fellay, Jacques; Kutalik, Zoltán; Hubaux, Jean-Pierre

    2017-08-01

    Due to the limited power of small-scale genome-wide association studies (GWAS), researchers tend to collaborate and establish a larger consortium in order to perform large-scale GWAS. Genome-wide association meta-analysis (GWAMA) is a statistical tool that aims to synthesize results from multiple independent studies to increase the statistical power and reduce false-positive findings of GWAS. However, it has been demonstrated that the aggregate data of individual studies are subject to inference attacks, hence privacy concerns arise when researchers share study data in GWAMA. In this article, we propose a secure quality control (SQC) protocol, which enables checking the quality of data in a privacy-preserving way without revealing sensitive information to a potential adversary. SQC employs state-of-the-art cryptographic and statistical techniques for privacy protection. We implement the solution in a meta-analysis pipeline with real data to demonstrate the efficiency and scalability on commodity machines. The distributed execution of SQC on a cluster of 128 cores for one million genetic variants takes less than one hour, which is a modest cost considering the 10-month time span usually observed for the completion of the QC procedure that includes timing of logistics. SQC is implemented in Java and is publicly available at https://github.com/acs6610987/secureqc. jean-pierre.hubaux@epfl.ch. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  9. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

    DEFF Research Database (Denmark)

    Murabito, Joanne M; White, Charles C; Kavousi, Maryam

    2012-01-01

    BACKGROUND: -Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based coh...

  10. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

    NARCIS (Netherlands)

    Murabito, Joanne M.; White, Charles C.; Kavousi, Maryam; Sun, Yan V.; Feitosa, Mary F.; Nambi, Vijay; Lamina, Claudia; Schillert, Arne; Coassin, Stefan; Bis, Joshua C.; Broer, Linda; Crawford, Dana C.; Franceschini, Nora; Frikke-Schmidt, Ruth; Haun, Margot; Holewijn, Suzanne; Huffman, Jennifer E.; Hwang, Shih-Jen; Kiechl, Stefan; Kollerits, Barbara; Montasser, May E.; Nolte, Ilja M.; Rudock, Megan E.; Senft, Andrea; Teumer, Alexander; van der Harst, Pim; Vitart, Veronique; Waite, Lindsay L.; Wood, Andrew R.; Wassel, Christina L.; Absher, Devin M.; Allison, Matthew A.; Amin, Najaf; Arnold, Alice; Asselbergs, Folkert W.; Aulchenko, Yurii; Bandinelli, Stefania; Barbalic, Maja; Boban, Mladen; Brown-Gentry, Kristin; Couper, David J.; Criqui, Michael H.; Dehghan, Abbas; den Heijer, Martin; Dieplinger, Benjamin; Ding, Jingzhong; Doerr, Marcus; Espinola-Klein, Christine; Felix, Stephan B.; Ferrucci, Luigi; Folsom, Aaron R.; Fraedrich, Gustav; Gibson, Quince; Goodloe, Robert; Gunjaca, Grgo; Haltmayer, Meinhard; Heiss, Gerardo; Hofman, Albert; Kieback, Arne; Kiemeney, Lambertus A.; Kolcic, Ivana; Kullo, Iftikhar J.; Kritchevsky, Stephen B.; Lackner, Karl J.; Li, Xiaohui; Lieb, Wolfgang; Lohman, Kurt; Meisinger, Christa; Melzer, David; Mohler, Emile R.; Mudnic, Ivana; Mueller, Thomas; Navis, Gerjan; Oberhollenzer, Friedrich; Olin, Jeffrey W.; O'Connell, Jeff; O'Donnell, Christopher J.; Palmas, Walter; Penninx, Brenda W.; Petersmann, Astrid; Polasek, Ozren; Psaty, Bruce M.; Rantner, Barbara; Rice, Ken; Rivadeneira, Fernando; Rotter, Jerome I.; Seldenrijk, Adrie; Stadler, Marietta; Summerer, Monika; Tanaka, Toshiko; Tybjaerg-Hansen, Anne; Uitterlinden, Andre G.; van Gilst, Wiek H.; Vermeulen, Sita H.; Wild, Sarah H.; Wild, Philipp S.; Willeit, Johann; Zeller, Tanja; Zemunik, Tatijana; Zgaga, Lina; Assimes, Themistocles L.; Blankenberg, Stefan; Campbell, Harry; Boerwinkle, Eric; Cooke, John P.; de Graaf, Jacqueline; Herrington, David; Kardia, Sharon L. R.; Mitchell, Braxton D.; Murray, Anna; Muenzel, Thomas; Newman, Anne B.; Oostra, Ben A.; Rudan, Igor; Shuldiner, Alan R.; Snieder, Harold; van Duijn, Cornelia M.; Voelker, Uwe; Wright, Alan F.; Wichmann, H. -Erich; Wilson, James F.; Witteman, Jacqueline C. M.; Liu, Yongmei; Hayward, Caroline; Borecki, Ingrid B.; Ziegler, Andreas; North, Kari E.; Cupples, L. Adrienne; Kronenberg, Florian; Dorr, M.; Munzel, T.; Volker, U.

    Background-Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.

  11. Statistical power and utility of meta-analysis methods for cross-phenotype genome-wide association studies.

    Science.gov (United States)

    Zhu, Zhaozhong; Anttila, Verneri; Smoller, Jordan W; Lee, Phil H

    2018-01-01

    Advances in recent genome wide association studies (GWAS) suggest that pleiotropic effects on human complex traits are widespread. A number of classic and recent meta-analysis methods have been used to identify genetic loci with pleiotropic effects, but the overall performance of these methods is not well understood. In this work, we use extensive simulations and case studies of GWAS datasets to investigate the power and type-I error rates of ten meta-analysis methods. We specifically focus on three conditions commonly encountered in the studies of multiple traits: (1) extensive heterogeneity of genetic effects; (2) characterization of trait-specific association; and (3) inflated correlation of GWAS due to overlapping samples. Although the statistical power is highly variable under distinct study conditions, we found the superior power of several methods under diverse heterogeneity. In particular, classic fixed-effects model showed surprisingly good performance when a variant is associated with more than a half of study traits. As the number of traits with null effects increases, ASSET performed the best along with competitive specificity and sensitivity. With opposite directional effects, CPASSOC featured the first-rate power. However, caution is advised when using CPASSOC for studying genetically correlated traits with overlapping samples. We conclude with a discussion of unresolved issues and directions for future research.

  12. A strategy analysis for genetic association studies with known inbreeding

    Directory of Open Access Journals (Sweden)

    del Giacco Stefano

    2011-07-01

    Full Text Available Abstract Background Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the beta-thalassemia, which is

  13. GPFrontend and GPGraphics: graphical analysis tools for genetic association studies.

    Science.gov (United States)

    Uebe, Steffen; Pasutto, Francesca; Krumbiegel, Mandy; Schanze, Denny; Ekici, Arif B; Reis, André

    2010-09-21

    Most software packages for whole genome association studies are non-graphical, purely text based programs originally designed to run with UNIX-like operating systems. Graphical output is often not intended or supposed to be performed with other command line tools, e.g. gnuplot. Using the Microsoft .NET 2.0 platform and Visual Studio 2005, we have created a graphical software package to analyze data from microarray whole genome association studies, both for a DNA-pooling based approach as well as regular single sample data. Part of this package was made to integrate with GenePool 0.8.2, a previously existing software suite for GNU/Linux systems, which we have modified to run in a Microsoft Windows environment. Further modifications cause it to generate some additional data. This enables GenePool to interact with the .NET parts created by us. The programs we developed are GPFrontend, a graphical user interface and frontend to use GenePool and create metadata files for it, and GPGraphics, a program to further analyze and graphically evaluate output of different WGA analysis programs, among them also GenePool. Our programs enable regular MS Windows users without much experience in bioinformatics to easily visualize whole genome data from a variety of sources.

  14. GPFrontend and GPGraphics: graphical analysis tools for genetic association studies

    Directory of Open Access Journals (Sweden)

    Schanze Denny

    2010-09-01

    Full Text Available Abstract Background Most software packages for whole genome association studies are non-graphical, purely text based programs originally designed to run with UNIX-like operating systems. Graphical output is often not intended or supposed to be performed with other command line tools, e.g. gnuplot. Results Using the Microsoft .NET 2.0 platform and Visual Studio 2005, we have created a graphical software package to analyze data from microarray whole genome association studies, both for a DNA-pooling based approach as well as regular single sample data. Part of this package was made to integrate with GenePool 0.8.2, a previously existing software suite for GNU/Linux systems, which we have modified to run in a Microsoft Windows environment. Further modifications cause it to generate some additional data. This enables GenePool to interact with the .NET parts created by us. The programs we developed are GPFrontend, a graphical user interface and frontend to use GenePool and create metadata files for it, and GPGraphics, a program to further analyze and graphically evaluate output of different WGA analysis programs, among them also GenePool. Conclusions Our programs enable regular MS Windows users without much experience in bioinformatics to easily visualize whole genome data from a variety of sources.

  15. A genome-wide association study meta-analysis of clinical fracture in 10,012 African American women

    Directory of Open Access Journals (Sweden)

    Kira C. Taylor

    2016-12-01

    Full Text Available Background: Osteoporosis is a major public health problem associated with excess disability and mortality. It is estimated that 50–70% of the variation in osteoporotic fracture risk is attributable to genetic factors. The purpose of this hypothesis-generating study was to identify possible genetic determinants of fracture among African American (AA women in a GWAS meta-analysis. Methods: Data on clinical fractures (all fractures except fingers, toes, face, skull or sternum were analyzed among AA female participants in the Women's Health Initiative (WHI (N = 8155, Cardiovascular Health Study (CHS (N = 504, BioVU (N = 704, Health ABC (N = 651, and the Johnston County Osteoarthritis Project (JoCoOA (N = 291. Affymetrix (WHI and Illumina (Health ABC, JoCoOA, BioVU, CHS GWAS panels were used for genotyping, and a 1:1 ratio of YRI:CEU HapMap haplotypes was used as an imputation reference panel. We used Cox proportional hazard models or logistic regression to evaluate the association of ~2.5 million SNPs with fracture risk, adjusting for ancestry, age, and geographic region where applicable. We conducted a fixed-effects, inverse variance-weighted meta-analysis. Genome-wide significance was set at P < 5 × 10−8. Results: One SNP, rs12775980 in an intron of SVIL on chromosome 10p11.2, reached genome-wide significance (P = 4.0 × 10−8. Although this SNP has a low minor allele frequency (0.03, there was no evidence for heterogeneity of effects across the studies (I2 = 0. This locus was not reported in any previous osteoporosis-related GWA studies. We also interrogated previously reported GWA-significant loci associated with fracture or bone mineral density in our data. One locus (SMOC1 generalized, but overall there was not substantial evidence of generalization. Possible reasons for the lack of generalization are discussed. Conclusion: This GWAS meta-analysis of fractures in African American women identified a potentially novel

  16. The association between mood state and chronobiological characteristics in bipolar I disorder: a naturalistic, variable cluster analysis-based study.

    Science.gov (United States)

    Gonzalez, Robert; Suppes, Trisha; Zeitzer, Jamie; McClung, Colleen; Tamminga, Carol; Tohen, Mauricio; Forero, Angelica; Dwivedi, Alok; Alvarado, Andres

    2018-02-19

    Multiple types of chronobiological disturbances have been reported in bipolar disorder, including characteristics associated with general activity levels, sleep, and rhythmicity. Previous studies have focused on examining the individual relationships between affective state and chronobiological characteristics. The aim of this study was to conduct a variable cluster analysis in order to ascertain how mood states are associated with chronobiological traits in bipolar I disorder (BDI). We hypothesized that manic symptomatology would be associated with disturbances of rhythm. Variable cluster analysis identified five chronobiological clusters in 105 BDI subjects. Cluster 1, comprising subjective sleep quality was associated with both mania and depression. Cluster 2, which comprised variables describing the degree of rhythmicity, was associated with mania. Significant associations between mood state and cluster analysis-identified chronobiological variables were noted. Disturbances of mood were associated with subjectively assessed sleep disturbances as opposed to objectively determined, actigraphy-based sleep variables. No associations with general activity variables were noted. Relationships between gender and medication classes in use and cluster analysis-identified chronobiological characteristics were noted. Exploratory analyses noted that medication class had a larger impact on these relationships than the number of psychiatric medications in use. In a BDI sample, variable cluster analysis was able to group related chronobiological variables. The results support our primary hypothesis that mood state, particularly mania, is associated with chronobiological disturbances. Further research is required in order to define these relationships and to determine the directionality of the associations between mood state and chronobiological characteristics.

  17. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

    Science.gov (United States)

    Zillikens, M Carola; Demissie, Serkalem; Hsu, Yi-Hsiang; Yerges-Armstrong, Laura M; Chou, Wen-Chi; Stolk, Lisette; Livshits, Gregory; Broer, Linda; Johnson, Toby; Koller, Daniel L; Kutalik, Zoltán; Luan, Jian'an; Malkin, Ida; Ried, Janina S; Smith, Albert V; Thorleifsson, Gudmar; Vandenput, Liesbeth; Hua Zhao, Jing; Zhang, Weihua; Aghdassi, Ali; Åkesson, Kristina; Amin, Najaf; Baier, Leslie J; Barroso, Inês; Bennett, David A; Bertram, Lars; Biffar, Rainer; Bochud, Murielle; Boehnke, Michael; Borecki, Ingrid B; Buchman, Aron S; Byberg, Liisa; Campbell, Harry; Campos Obanda, Natalia; Cauley, Jane A; Cawthon, Peggy M; Cederberg, Henna; Chen, Zhao; Cho, Nam H; Jin Choi, Hyung; Claussnitzer, Melina; Collins, Francis; Cummings, Steven R; De Jager, Philip L; Demuth, Ilja; Dhonukshe-Rutten, Rosalie A M; Diatchenko, Luda; Eiriksdottir, Gudny; Enneman, Anke W; Erdos, Mike; Eriksson, Johan G; Eriksson, Joel; Estrada, Karol; Evans, Daniel S; Feitosa, Mary F; Fu, Mao; Garcia, Melissa; Gieger, Christian; Girke, Thomas; Glazer, Nicole L; Grallert, Harald; Grewal, Jagvir; Han, Bok-Ghee; Hanson, Robert L; Hayward, Caroline; Hofman, Albert; Hoffman, Eric P; Homuth, Georg; Hsueh, Wen-Chi; Hubal, Monica J; Hubbard, Alan; Huffman, Kim M; Husted, Lise B; Illig, Thomas; Ingelsson, Erik; Ittermann, Till; Jansson, John-Olov; Jordan, Joanne M; Jula, Antti; Karlsson, Magnus; Khaw, Kay-Tee; Kilpeläinen, Tuomas O; Klopp, Norman; Kloth, Jacqueline S L; Koistinen, Heikki A; Kraus, William E; Kritchevsky, Stephen; Kuulasmaa, Teemu; Kuusisto, Johanna; Laakso, Markku; Lahti, Jari; Lang, Thomas; Langdahl, Bente L; Launer, Lenore J; Lee, Jong-Young; Lerch, Markus M; Lewis, Joshua R; Lind, Lars; Lindgren, Cecilia; Liu, Yongmei; Liu, Tian; Liu, Youfang; Ljunggren, Östen; Lorentzon, Mattias; Luben, Robert N; Maixner, William; McGuigan, Fiona E; Medina-Gomez, Carolina; Meitinger, Thomas; Melhus, Håkan; Mellström, Dan; Melov, Simon; Michaëlsson, Karl; Mitchell, Braxton D; Morris, Andrew P; Mosekilde, Leif; Newman, Anne; Nielson, Carrie M; O'Connell, Jeffrey R; Oostra, Ben A; Orwoll, Eric S; Palotie, Aarno; Parker, Stephen C J; Peacock, Munro; Perola, Markus; Peters, Annette; Polasek, Ozren; Prince, Richard L; Räikkönen, Katri; Ralston, Stuart H; Ripatti, Samuli; Robbins, John A; Rotter, Jerome I; Rudan, Igor; Salomaa, Veikko; Satterfield, Suzanne; Schadt, Eric E; Schipf, Sabine; Scott, Laura; Sehmi, Joban; Shen, Jian; Soo Shin, Chan; Sigurdsson, Gunnar; Smith, Shad; Soranzo, Nicole; Stančáková, Alena; Steinhagen-Thiessen, Elisabeth; Streeten, Elizabeth A; Styrkarsdottir, Unnur; Swart, Karin M A; Tan, Sian-Tsung; Tarnopolsky, Mark A; Thompson, Patricia; Thomson, Cynthia A; Thorsteinsdottir, Unnur; Tikkanen, Emmi; Tranah, Gregory J; Tuomilehto, Jaakko; van Schoor, Natasja M; Verma, Arjun; Vollenweider, Peter; Völzke, Henry; Wactawski-Wende, Jean; Walker, Mark; Weedon, Michael N; Welch, Ryan; Wichmann, H-Erich; Widen, Elisabeth; Williams, Frances M K; Wilson, James F; Wright, Nicole C; Xie, Weijia; Yu, Lei; Zhou, Yanhua; Chambers, John C; Döring, Angela; van Duijn, Cornelia M; Econs, Michael J; Gudnason, Vilmundur; Kooner, Jaspal S; Psaty, Bruce M; Spector, Timothy D; Stefansson, Kari; Rivadeneira, Fernando; Uitterlinden, André G; Wareham, Nicholas J; Ossowski, Vicky; Waterworth, Dawn; Loos, Ruth J F; Karasik, David; Harris, Tamara B; Ohlsson, Claes; Kiel, Douglas P

    2017-07-19

    Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

  18. High performance computing enabling exhaustive analysis of higher order single nucleotide polymorphism interaction in Genome Wide Association Studies.

    Science.gov (United States)

    Goudey, Benjamin; Abedini, Mani; Hopper, John L; Inouye, Michael; Makalic, Enes; Schmidt, Daniel F; Wagner, John; Zhou, Zeyu; Zobel, Justin; Reumann, Matthias

    2015-01-01

    Genome-wide association studies (GWAS) are a common approach for systematic discovery of single nucleotide polymorphisms (SNPs) which are associated with a given disease. Univariate analysis approaches commonly employed may miss important SNP associations that only appear through multivariate analysis in complex diseases. However, multivariate SNP analysis is currently limited by its inherent computational complexity. In this work, we present a computational framework that harnesses supercomputers. Based on our results, we estimate a three-way interaction analysis on 1.1 million SNP GWAS data requiring over 5.8 years on the full "Avoca" IBM Blue Gene/Q installation at the Victorian Life Sciences Computation Initiative. This is hundreds of times faster than estimates for other CPU based methods and four times faster than runtimes estimated for GPU methods, indicating how the improvement in the level of hardware applied to interaction analysis may alter the types of analysis that can be performed. Furthermore, the same analysis would take under 3 months on the currently largest IBM Blue Gene/Q supercomputer "Sequoia" at the Lawrence Livermore National Laboratory assuming linear scaling is maintained as our results suggest. Given that the implementation used in this study can be further optimised, this runtime means it is becoming feasible to carry out exhaustive analysis of higher order interaction studies on large modern GWAS.

  19. Methodological issues of genetic association studies.

    Science.gov (United States)

    Simundic, Ana-Maria

    2010-12-01

    Genetic association studies explore the association between genetic polymorphisms and a certain trait, disease or predisposition to disease. It has long been acknowledged that many genetic association studies fail to replicate their initial positive findings. This raises concern about the methodological quality of these reports. Case-control genetic association studies often suffer from various methodological flaws in study design and data analysis, and are often reported poorly. Flawed methodology and poor reporting leads to distorted results and incorrect conclusions. Many journals have adopted guidelines for reporting genetic association studies. In this review, some major methodological determinants of genetic association studies will be discussed.

  20. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes

    DEFF Research Database (Denmark)

    Barrett, Jeffrey C; Clayton, David G; Concannon, Patrick

    2009-01-01

    Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7......,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P

  1. Association between Myocardial Infarction and Periodontitis: a Meta-Analysis of Case-Control Studies

    Directory of Open Access Journals (Sweden)

    Quan Shi

    2016-11-01

    Full Text Available AbstractBackground and Objective: Many clinical researches have been carried out to investigate the relationship between myocardial infarction (MI and periodontitis. Despite most of them indicated that the periodontitis may be associated with an increased risk of MI, the findings and study types of these studies have been inconsistent. The goal of this meta-analysis was to critically assess the strength of the association between MI and periodontitis in case-control studies.Methods: PubMed and the Cochrane Library were searched for eligible case-control studies reporting relevant parameters that compared periodontal status between MI and control subjects. The odds ratios (ORs and 95% confidence intervals (CIs from each study were pooled to estimate the strength of the association between MI and periodontitis. The mean differences and 95% CIs for periodontal-related parameters were calculated to determine their overall effects.Results: Seventeen studies including a total of 3456 MI patients and 3875 non-MI control subjects were included. The pooled OR for the association between MI and periodontitis was 2.531 (95% CI: 1.927-3.324. The mean differences (95% CIs for clinical attachment loss, probing depth, bleeding on probing, plaque index, and the number of missing teeth were 1.000 (0.726-1.247, 1.209 (0.538-1.880, 0.342 (0.129-0.555, 0.383 (0.205-0.560, and 4.122 (2.012-6.232, respectively. Conclusion: With the current evidence, the results support the presence of a significant association between MI and periodontitis. Moreover, MI patients had worse periodontal and oral hygiene status and fewer teeth than did control subjects. More high-quality and well-designed studies focusing on the casual relationship between MI and periodontitis should be conducted in the future.

  2. Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies.

    Directory of Open Access Journals (Sweden)

    Kai Zhang

    Full Text Available BACKGROUND: The associations between vitamin D receptor (VDR gene polymorphisms and breast cancer risk were comprehensively investigated to clarify issues that remain controversial. METHODOLOGY/PRINCIPAL FINDINGS: An electronic search was conducted of several databases, including PubMed, the Cochrane library, Web of Science, EMBASE, CBM and CNKI, for papers that describe the association between Fok1, poly-A repeat, Bsm1, Taq1 or Apa1 polymorphisms of the VDR gene and breast cancer risk. Summary odds ratios and 95% confidence intervals (CI were estimated based on a fixed-effect model (FEM or random-effect model (REM, depending on the absence or presence of significant heterogeneity. A total of 39 studies met the inclusion criteria. A meta-analysis of high-quality studies showed that the Fok1 polymorphism of the VDR gene was associated with an increased risk of breast cancer (ff vs. Ff+FF, OR: 1.09, 95%CI: 1.02 to 1.16, p = 0.007. No significant associations were observed between the other polymorphisms and breast cancer risk. No positive results were detected by pooling the results of all relevant studies. CONCLUSION: A meta-analysis of high-quality studies demonstrated that the Fok1 polymorphism of the VDR gene was closely associated with breast cancer risk.

  3. Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jinhong Zhu

    Full Text Available BACKGROUND: Excision repair cross-complimentary group 1 (ERCC1 is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial. OBJECTIVES: An updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following ERCC1 polymorphisms: rs11615 (T>C, rs3212986 (C>A, rs3212961 (A>C, rs3212948 (G>C, rs2298881 (C>A. METHODS: Several major databases (MEDLINE, EMBASE and Scopus and the Chinese Biomedical database were searched for eligible studies. Crude odds ratios (ORs with 95% confidence intervals (CIs were used to measure the strength of associations. RESULTS: Sixteen studies with 10,106 cases and 13,238 controls were included in this meta-analysis. Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls suggested a significant association of ERCC1 rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04-1.48, P = 0.02. However, such an association was disproportionately driven by a single study. Removal of that study led to null association. Moreover, initial analyses suggested that ERCC1 rs11615 exerts a more profound effect on the susceptibility of non-smokers to lung cancer than that of smokers. Moreover, no statistically significant association was found between remaining ERCC1 polymorphisms of interest and lung cancer risk, except for rs3212948 variation (heterozygous: CG vs.GG, OR = 0.78, 95% CI: 0.67-0.90, P = 0.001; dominant: CG/CC vs.GG, OR = 0.79, 95% CI: 0.69-0.91, P = 0.001. CONCLUSION: Overall, this meta-analysis suggests that ERCC1 rs3212948 G>C, but not others, is a lung cancer risk-associated polymorphism. Carefully

  4. A meta-analysis of four genome-wide association studies of survival to age 90 years or older

    DEFF Research Database (Denmark)

    Newman, Anne B; Walter, Stefan; Lunetta, Kathryn L

    2010-01-01

    BACKGROUND: Genome-wide association studies (GWAS) may yield insights into longevity. METHODS: We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart S...

  5. A functional data analysis approach for genetic association studies

    OpenAIRE

    Reimherr, Matthew; Nicolae, Dan

    2014-01-01

    We present a new method based on Functional Data Analysis (FDA) for detecting associations between one or more scalar covariates and a longitudinal response, while correcting for other variables. Our methods exploit the temporal structure of longitudinal data in ways that are otherwise difficult with a multivariate approach. Our procedure, from an FDA perspective, is a departure from more established methods in two key aspects. First, the raw longitudinal phenotypes are assembled into functio...

  6. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

    DEFF Research Database (Denmark)

    Postmus, Iris; Warren, Helen R; Trompet, Stella

    2016-01-01

    BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We performed...... a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p

  7. Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies.

    Directory of Open Access Journals (Sweden)

    Qiliu Peng

    Full Text Available OBJECTIVE: Cyclooxygenase-2 (COX-2 is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. METHODS: All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs together with their 95% confidence intervals (CIs. RESULTS: Ten studies with 6,774 cases and 9,772 controls were included for -1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for -765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to -765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113-1.760, P = 0.004 and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295-3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297-3.970, P = 0.004. In subgroup analysis according to source of control, no significant association was detected. With respect to -1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses. CONCLUSIONS: The present meta-analysis suggests that the COX-2 -765G>C polymorphism may be a risk factor for

  8. Associations between Obesity and Spinal Diseases: A Medical Expenditure Panel Study Analysis

    Directory of Open Access Journals (Sweden)

    Binwu Sheng

    2017-02-01

    Full Text Available Background: The link between body weight status and spinal diseases has been suggested by a number of cross-sectional and cohort studies with a limited range of patient populations. No population-representative samples have been used to examine the link between obesity and spinal diseases. The present study is based on a nationally representative sample drawn from the Medical Expenditure Panel Survey. Methods: Using the cross-sectional sample of the 2014 Medical Expenditure Panel Study, we built four weighted logistic regression analyses of the associations between body weight status and the following four spinal diseases: low back pain, spondylosis, other cervical disorders and intervertebral disc disorder (IDD. Each respondent’s body weight status was used as the key independent variable with three categories: normal/underweight, overweight, and obese. We controlled for marital status, gender, age, smoking status, household income, health insurance coverage, educational attainment and the use of health services for other major categories of diseases. Results: A total sample of 23,048 respondents was used in our analysis. Overweight and obese respondents, as compared to normal/underweight respondents, were more likely to develop lower back problems (Overweight: logged odds = 0.218, p < 0.01; Obese: logged odds = 0.395, p < 0.001 and IDD (Overweight: logged odds = 0.441, p < 0.05; Obese: logged odds = 0.528, p < 0.001. The associations between bodyweight status and spondylitis were statistically insignificant (Overweight: logged odds = 0.281, p = 0.442; Obese: logged odds = 0.680, p = 0.104. The associations between body weight status and other cervical disorders (Overweight: logged odds = −0.116, p = 0.304; Obese: logged odds = −0.160, p = 0.865 were statistically insignificant. Conclusions: As the first study using a national sample to study bodyweight and spinal diseases, our paper supports the hypothesis that obesity adds to the burden

  9. [Association between chronic periodontitis and hyperlipidemia: a Meta-analysis based on observational studies].

    Science.gov (United States)

    Lianhui, Yang; Meifei, Lian; Zhongyue, Hu; Yunzhi, Feng

    2017-08-01

    Objective The aim of this study is to evaluate the relationship between periodontitis and hyperlipidemia risks through Meta-analysis. Methods Two researchers conducted an electronic search on PubMed, Cochrane Library, Embase, CBM, CNKI, Wanfang and VIP databases established until July 2016 for observational studies on the association between periodontitis and hyperlipidemia. The language used was limited to Chinese and English. After data extraction and quality evaluation of included trials, Meta-analysis was conducted using the RevMan 5.3 software. The GRADE 3.6 software was used to evaluate the quality level of the evidence. Results Six case-control studies and one cohort study were included. The results of Meta-analysis showed that serum triglyceride (TG) in patients with periodontitis was significantly higher than that of the periodontal health group (MD=50.50, 95% confidence interval=39.57-61.42, Pchronic periodontitis were 4.73 times (OR=4.73, 95% confidence interval=2.74-8.17, Pperiodontal healthy patients. No significant difference was observed between the group with high-density lipoprotein cholesterol (HDL-C) and that with low density lipoprotein cholesterol (LDL-C). Conclusion Current evidence indicates that a correlation exists between chronic periodontitis and hyperlipidemia, and chronic periodontitis is an independent risk factor for hyperlipidemia, especially for TC and TG in serum.

  10. Gene ontology analysis of pairwise genetic associations in two genome-wide studies of sporadic ALS

    Directory of Open Access Journals (Sweden)

    Kim Nora

    2012-07-01

    Full Text Available Abstract Background It is increasingly clear that common human diseases have a complex genetic architecture characterized by both additive and nonadditive genetic effects. The goal of the present study was to determine whether patterns of both additive and nonadditive genetic associations aggregate in specific functional groups as defined by the Gene Ontology (GO. Results We first estimated all pairwise additive and nonadditive genetic effects using the multifactor dimensionality reduction (MDR method that makes few assumptions about the underlying genetic model. Statistical significance was evaluated using permutation testing in two genome-wide association studies of ALS. The detection data consisted of 276 subjects with ALS and 271 healthy controls while the replication data consisted of 221 subjects with ALS and 211 healthy controls. Both studies included genotypes from approximately 550,000 single-nucleotide polymorphisms (SNPs. Each SNP was mapped to a gene if it was within 500 kb of the start or end. Each SNP was assigned a p-value based on its strongest joint effect with the other SNPs. We then used the Exploratory Visual Analysis (EVA method and software to assign a p-value to each gene based on the overabundance of significant SNPs at the α = 0.05 level in the gene. We also used EVA to assign p-values to each GO group based on the overabundance of significant genes at the α = 0.05 level. A GO category was determined to replicate if that category was significant at the α = 0.05 level in both studies. We found two GO categories that replicated in both studies. The first, ‘Regulation of Cellular Component Organization and Biogenesis’, a GO Biological Process, had p-values of 0.010 and 0.014 in the detection and replication studies, respectively. The second, ‘Actin Cytoskeleton’, a GO Cellular Component, had p-values of 0.040 and 0.046 in the detection and replication studies, respectively. Conclusions Pathway

  11. Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

    Science.gov (United States)

    Manitz, Juliane; Burger, Patricia; Amos, Christopher I.; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike

    2017-01-01

    The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility. PMID:28785300

  12. Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies.

    Science.gov (United States)

    Friedrichs, Stefanie; Manitz, Juliane; Burger, Patricia; Amos, Christopher I; Risch, Angela; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike; Hofner, Benjamin

    2017-01-01

    The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.

  13. Association between varicocele grade and semen analysis parameter

    Directory of Open Access Journals (Sweden)

    Ira Ariyati

    2018-02-01

    Full Text Available Background: Varicocele is a condition characterized by elongation, dilatation and tortuousity of spermatic vein in pampiniform plexus. Approximately 50% of infertility cases among men are caused by varicocele. The varicocele may affect the components of sperm. This study aimed to determine the association between varicocele grade based on ultrasound Doppler examination and sperm concentration, sperm motility, and sperm morphology based on semen analysis examination.Methods: This was a descriptive, cross-sectional study which used secondary data from 85 patients that visited Department of Urology, Cipto Mangunkusumo Hospital, then underwent ultrasonography examination at Department of Radiology, Cipto Mangunkusumo Hospital and semen analysis examination at Department of Obstetrics and Gynecology, Cipto Mangunkusumo General Hospital.Results: Varicocele grade was significantly associated with sperm morphology, concentration and motility (all p<0.05. Significant association was found between maximum condition and semen analysis component.Conclusion: Varicocele grade may affect semen analysis component.

  14. Association between fat mass- and obesity-associated (FTO gene polymorphism and polycystic ovary syndrome: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xianli Cai

    Full Text Available Many studies have investigated the relationship between FTO gene polymorphism and polycystic ovary syndrome (PCOS susceptibility but revealed mixed results. In this study, we aimed to perform a meta-analysis to clarify this association.Published literature from PubMed, Embase and CNKI was retrieved. Meta-analysis was performed to calculate pooled odds ratio (OR with 95% confidence interval (CI using the random- or fix- effects model.A total of 5 studies (4778 cases and 4272 controls were included in our meta-analysis. The results suggested that FTO rs9939609 polymorphism (or its proxy was marginally associated with PCOS risk after adjustment for body mass index (BMI (OR = 1.26; 95%CI: 1.02-1.55. However, the marginal association was not stable after sensitivity analysis. In the subgroup analysis by ethnicity, the association was significant in East Asians (OR = 1.43, 95%CI = 1.30-1.59 but not in Caucasians (OR = 1.04, 95%CI = 0.85-1.29.Our present meta-analysis indicated that FTO rs9939609 polymorphism (or its proxy might not be associated with risk of PCOS in overall population. However, in East Asians, there might be a direct association between FTO variant and PCOS risk, which is independent of BMI (adiposity.

  15. Evaluation of the association between acne and smoking: systematic review and meta-analysis of cross-sectional studies

    Directory of Open Access Journals (Sweden)

    Alice Mannocci

    2010-09-01

    Full Text Available

    Background: Acne vulgaris is one of the most common skin diseases with a multifactorial pathogenesis. Examination of the literature regarding the contribution of smoking to acne shows contradictory results. The aim of this study was to undertake a systematic review of the literature and meta-analysis about the association between acne and smoking.

    Methods: A systematic review and meta-analysis, when possible were performed. The literature review was based on Pubmed, Scopus and Google Scholar searches using the keywords “(smoking OR tobacco OR nicotine OR cigarettes AND acne”. Only cross-sectional studies were included. Meta-analyses were performed using the RevMan software version 5 for Windows. Four different meta-analyses were carried out: one evaluating the association between smoking habit and acne, one including data stratified by gender, one for studies with a quality score > 6, and one relating to acne classification.

    Results: Six studies were selected. The first meta-analysis, including all studies, showed a non significant role of smoke in the development of acne: OR 1.05 (95% CI: 0.66–1.67 with random effect estimate. The second meta-analyses, including data stratified by gender, showed a OR=0.99 (95% CI: 0.57–1.73 for males and a OR of 1.45 (95% CI: 0.08–24.64 for females, using random effect for the heterogeneity in both cases. The third meta-analysis, included studies with a quality score >6 resulted in an estimated OR= 0.69 (95% CI: 0.55–0.85: in this case it was possible to use the fixed effect estimate. The last meta-analysis, concerning the severity grading, showed a non-significant result: OR=1.09 (95% CI: 0.61–1.95 using the random effect approach.

    Conclusions: The first two meta-analyses found no signification association between smoking and

  16. Remote sensing and spatial analysis based study for detecting deforestation and the associated drivers

    Science.gov (United States)

    El-Abbas, Mustafa M.; Csaplovics, Elmar; Deafalla, Taisser H.

    2013-10-01

    Nowadays, remote-sensing technologies are becoming increasingly interlinked to the issue of deforestation. They offer a systematized and objective strategy to document, understand and simulate the deforestation process and its associated causes. In this context, the main goal of this study, conducted in the Blue Nile region of Sudan, in which most of the natural habitats were dramatically destroyed, was to develop spatial methodologies to assess the deforestation dynamics and its associated factors. To achieve that, optical multispectral satellite scenes (i.e., ASTER and LANDSAT) integrated with field survey in addition to multiple data sources were used for the analyses. Spatiotemporal Object Based Image Analysis (STOBIA) was applied to assess the change dynamics within the period of study. Broadly, the above mentioned analyses include; Object Based (OB) classifications, post-classification change detection, data fusion, information extraction and spatial analysis. Hierarchical multi-scale segmentation thresholds were applied and each class was delimited with semantic meanings by a set of rules associated with membership functions. Consequently, the fused multi-temporal data were introduced to create detailed objects of change classes from the input LU/LC classes. The dynamic changes were quantified and spatially located as well as the spatial and contextual relations from adjacent areas were analyzed. The main finding of the present study is that, the forest areas were drastically decreased, while the agrarian structure in conversion of forest into agricultural fields and grassland was the main force of deforestation. In contrast, the capability of the area to recover was clearly observed. The study concludes with a brief assessment of an 'oriented' framework, focused on the alarming areas where serious dynamics are located and where urgent plans and interventions are most critical, guided with potential solutions based on the identified driving forces.

  17. Strain-based HLA association analysis identified HLA-DRB1*09:01 associated with modern strain tuberculosis.

    Science.gov (United States)

    Toyo-Oka, L; Mahasirimongkol, S; Yanai, H; Mushiroda, T; Wattanapokayakit, S; Wichukchinda, N; Yamada, N; Smittipat, N; Juthayothin, T; Palittapongarnpim, P; Nedsuwan, S; Kantipong, P; Takahashi, A; Kubo, M; Sawanpanyalert, P; Tokunaga, K

    2017-09-01

    Tuberculosis (TB) occurs as a result of complex interactions between the host immune system and pathogen virulence factors. Human leukocyte antigen (HLA) class II molecules play an important role in the host immune system. However, no study has assessed the association between HLA class II genes and susceptibility to TB caused by specific strains. This study investigated the possible association of HLA class II genes with TB caused by modern and ancient Mycobacterium tuberculosis (MTB). The study included 682 patients with TB and 836 control subjects who were typed for HLA-DRB1 and HLA-DQB1 alleles. MTB strains were classified using a large sequence polymorphism typing method. Association analysis was performed using common HLA alleles and haplotypes in different MTB strains. HLA association analysis of patients infected with modern MTB strains showed significant association for HLA-DRB1*09:01 (odds ratio [OR] = 1.82; P-value = 9.88 × 10 -4 ) and HLA-DQB1*03:03 alleles (OR = 1.76; P-value = 1.31 × 10 -3 ) with susceptibility to TB. Haplotype analysis confirmed that these alleles were in strong linkage disequilibrium and did not exert an interactive effect. Thus, the results of this study showed an association between HLA class II genes and susceptibility to TB caused by modern MTB strains, suggesting the importance of strain-specific analysis to determine susceptibility genes associated with TB. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Dose-Response Association Between Physical Activity and Incident Hypertension: A Systematic Review and Meta-Analysis of Cohort Studies.

    Science.gov (United States)

    Liu, Xuejiao; Zhang, Dongdong; Liu, Yu; Sun, Xizhuo; Han, Chengyi; Wang, Bingyuan; Ren, Yongcheng; Zhou, Junmei; Zhao, Yang; Shi, Yuanyuan; Hu, Dongsheng; Zhang, Ming

    2017-05-01

    Despite the inverse association between physical activity (PA) and incident hypertension, a comprehensive assessment of the quantitative dose-response association between PA and hypertension has not been reported. We performed a meta-analysis, including dose-response analysis, to quantitatively evaluate this association. We searched PubMed and Embase databases for articles published up to November 1, 2016. Random effects generalized least squares regression models were used to assess the quantitative association between PA and hypertension risk across studies. Restricted cubic splines were used to model the dose-response association. We identified 22 articles (29 studies) investigating the risk of hypertension with leisure-time PA or total PA, including 330 222 individuals and 67 698 incident cases of hypertension. The risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92-0.96) with each 10 metabolic equivalent of task h/wk increment of leisure-time PA. We found no evidence of a nonlinear dose-response association of PA and hypertension ( P nonlinearity =0.094 for leisure-time PA and 0.771 for total PA). With the linear cubic spline model, when compared with inactive individuals, for those who met the guidelines recommended minimum level of moderate PA (10 metabolic equivalent of task h/wk), the risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92-0.97). This meta-analysis suggests that additional benefits for hypertension prevention occur as the amount of PA increases. © 2017 American Heart Association, Inc.

  19. Association between Work-Related Stress and Risk for Type 2 Diabetes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

    Science.gov (United States)

    Sui, Hua; Sun, Nijing; Zhan, Libin; Lu, Xiaoguang; Chen, Tuo; Mao, Xinyong

    2016-01-01

    The prevalence of type 2 diabetes is increasing rapidly around the world. Work-related stress is thought to be a major risk factor for type 2 diabetes; however, this association has not been widely studied, and the findings that have been reported are inconsistent. Therefore, we conducted a meta-analysis of prospective cohort studies to explore the association between work-related stress and risk for type 2 diabetes. A systematic literature search and manual search limited to articles published in English were performed to select the prospective cohort studies evaluated the association between work-related stress and risk for type 2 diabetes up to September 2014 from four electronic databases including PubMed, EMBASE, the Cochrane Library and Web of Science. A random-effects model was used to estimate the overall risk. No significant association was found between work-related stress and risk for type 2 diabetes based on meta-analysis of seven prospective cohort studies involving 214,086 participants and 5,511 cases (job demands: relative risk 0.94 [95% confidence interval 0.72-1.23]; decision latitude: relative risk 1.16 [0.85-1.58]; job strain: relative risk 1.12 [.0.95-1.32]). However, an association between work-related stress and risk for type 2 diabetes was observed in women (job strain: relative risk 1.22 [1.01-1.46]) (P = 0.04). A sensitivity analysis conducted by excluding one study in each turn yielded similar results. No publication bias was detected with a funnel plot despite the limited number of studies included in the analysis. The results of this meta-analysis did not confirm a direct association between work-related stress and risk for type 2 diabetes. In subgroup analyses we found job strain was a risk factor for type 2 diabetes in women.

  20. Research Guidelines in the Era of Large-scale Collaborations: An Analysis of Genome-wide Association Study Consortia

    Science.gov (United States)

    Austin, Melissa A.; Hair, Marilyn S.; Fullerton, Stephanie M.

    2012-01-01

    Scientific research has shifted from studies conducted by single investigators to the creation of large consortia. Genetic epidemiologists, for example, now collaborate extensively for genome-wide association studies (GWAS). The effect has been a stream of confirmed disease-gene associations. However, effects on human subjects oversight, data-sharing, publication and authorship practices, research organization and productivity, and intellectual property remain to be examined. The aim of this analysis was to identify all research consortia that had published the results of a GWAS analysis since 2005, characterize them, determine which have publicly accessible guidelines for research practices, and summarize the policies in these guidelines. A review of the National Human Genome Research Institute’s Catalog of Published Genome-Wide Association Studies identified 55 GWAS consortia as of April 1, 2011. These consortia were comprised of individual investigators, research centers, studies, or other consortia and studied 48 different diseases or traits. Only 14 (25%) were found to have publicly accessible research guidelines on consortia websites. The available guidelines provide information on organization, governance, and research protocols; half address institutional review board approval. Details of publication, authorship, data-sharing, and intellectual property vary considerably. Wider access to consortia guidelines is needed to establish appropriate research standards with broad applicability to emerging forms of large-scale collaboration. PMID:22491085

  1. Is coffee consumption associated with a lower level of serum C-reactive protein? A meta-analysis of observational studies.

    Science.gov (United States)

    Zhang, Yi; Zhang, Dian-Zhong

    2018-02-06

    The association between coffee consumption and the level of C-reactive protein (CRP) has been evaluated in several epidemiological studies with conflicting results. This study aims to examine the relationship between coffee consumption and the serum CRP level. A comprehensive literature search up to August 2017, using PUBMED, EMBASE and Web of Science databases, was conducted to identify the relevant observational studies that examined the association between coffee consumption and the serum CRP level. A total of nine cross-sectional studies were included in this meta-analysis. According to the combined standard mean difference (SMD) between the highest and the lowest coffee intake category, coffee consumption was associated with a lower level of serum CRP level (SMD = -0.34, 95%CI: -0.62 to -0.06; p = .016). Subgroup analysis for CRP marker showed that coffee consumption was associated with a lower level of serum high-sensitivity CRP (hsCRP) (SMD = -0.51, 95%CI: -0.88 to -0.14; p = .007), but not standard CRP (SMD = 0.02, 95%CI: -0.28 to 0.32; p = .913). The existing evidence suggested that coffee consumption was associated with a lower level of serum CRP. More well-designed prospective cohort studies are needed to elaborate the concerned issues further.

  2. Association between tea consumption and risk of cognitive disorders: A dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Liu, Xueying; Du, Xiaoyuan; Han, Guanying; Gao, Wenyuan

    2017-06-27

    The epidemiological evidence for a dose-response relationship between tea consumption and risk of cognitive disorders is sparse. The aim of the study was to summarize the evidence for the association of tea consumption with risk of cognitive disorders and assess the dose-response relationship. We searched electronic databases of Pubmed, Embase, and Cochrane Library (from 1965 to Jan 19, 2017) for eligible studies that published in the international journals. A random-effects model was used to pool the most adjusted odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Seventeen studies involving 48,435 participants were included in our study. The meta-analysis showed that a higher tea consumption was associated with a significant reduction in the risk of cognitive disorders (OR=0.73, 95% CI: 0.65-0.82). When considering the specific types of tea consumption, the significantly inverse association is only found in green tea consumption (OR=0.64, 95% CI: 0.53-0.77) but not in black/oolong tea consumption (OR=0.75, 95% CI: 0.55-1.01). Dose-response meta-analysis indicated that tea consumption is linearly associated with a reduced risk of cognitive disorders. An increment of 100 ml/day, 300 ml/day, and 500 ml/day of tea consumption was associated with a 6% (OR=0.94, 95% CI: 0.92-0.96), 19% (OR=0.81, 95% CI: 0.74-0.88), and 29% (OR=0.71, 95% CI: 0.62-0.82) lower risk of cognitive disorders. Tea consumption is inversely and linearly related to the risk of cognitive disorders. More studies are needed to further confirm our findings.

  3. Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis.

    Science.gov (United States)

    Feng, Mei; Zhu, Jing; Liang, Liqun; Zeng, Ni; Wu, Yanqiu; Wan, Chun; Shen, Yongchun; Wen, Fuqiang

    2017-04-01

    Pleural effusion is one of the most common complications of lung adenocarcinoma and is diagnostically challenging. This study aimed to investigate the diagnostic performance of carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, and cancer antigen (CA) 19-9 for lung adenocarcinoma-associated malignant pleural effusion (MPE) through a validation study and meta-analysis. Pleural effusion samples were collected from 81 lung adenocarcinoma-associated MPEs and 96 benign pleural effusions. CEA, CYFRA 21-1, and CA19-9 were measured by electrochemiluminescence immunoassay. The capacity of tumor markers was assessed with receiver operating characteristic curve analyses and the area under the curve (AUC) was calculated. Standard methods for meta-analysis of diagnostic studies were used to summarize the diagnostic performance of CEA, CYFRA 21-1, and CA19-9 for lung adenocarcinoma-associated MPE. The pleural levels of CEA, CYFRA 21-1, and CA19-9 were significantly increased in lung adenocarcinoma-associated MPE compared to benign pleural effusion. The cut-off points for CEA, CYFRA 21-1, and CA19-9 were optimally set at 4.55 ng/ml, 43.10 μg/ml, and 12.89 U/ml, and corresponding AUCs were 0.93, 0.85, and 0.81, respectively. The combination of CEA, CYFRA 21-1, and CA19-9 increased the sensitivity to 95.06%, with an AUC of 0.95. Eight studies were included in this meta-analysis. CEA showed the best diagnostic performance with pooled sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of 0.75, 0.96, 16.01, 0.23, and 81.49, respectively. The AUC was 0.93. CEA, CYFRA 21-1, and CA19-9 play a role in the diagnosis of lung adenocarcinoma-associated MPE. The combination of these tumor markers increases the diagnostic accuracy.

  4. Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-Wide Association Studies

    DEFF Research Database (Denmark)

    Joshi, Amit D; Andersson, Charlotte; Buch, Stephan

    2016-01-01

    discovery studies (8720 cases and 55,152 controls). We performed an inverse variance weighted, fixed-effects meta-analysis of study-specific estimates to identify single-nucleotide polymorphisms that were associated independently with gallstone disease. Associations were replicated in 6489 cases and 62...... in TM4SF4 (OR, 1.12; 95% CI, 1.08-1.16; P = 6.09 × 10(-11)), rs2547231 in SULT2A1 (encodes a sulfoconjugation enzyme that acts on hydroxysteroids and cholesterol-derived sterol bile acids) (OR, 1.17; 95% CI, 1.12-1.21; P = 2.24 × 10(-10)), rs1260326 in glucokinase regulatory protein (OR, 1.12; 95% CI, 1...

  5. Prediction of disease and phenotype associations from genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Stephanie N Lewis

    Full Text Available Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases.Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits.The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

  6. Patent foramen ovale, ischemic stroke and migraine: systematic review and stratified meta-analysis of association studies.

    Science.gov (United States)

    Davis, Daniel; Gregson, John; Willeit, Peter; Stephan, Blossom; Al-Shahi Salman, Rustam; Brayne, Carol

    2013-01-01

    Observational data have reported associations between patent foramen ovale (PFO), cryptogenic stroke and migraine. However, randomized trials of PFO closure do not demonstrate a clear benefit either because the underlying association is weaker than previously suggested or because the trials were underpowered. In order to resolve the apparent discrepancy between observational data and randomized trials, we investigated associations between (1) migraine and ischemic stroke, (2) PFO and ischemic stroke, and (3) PFO and migraine. Eligibility criteria were consistent; including all studies with specifically defined exposures and outcomes unrestricted by language. We focused on studies at lowest risk of bias by stratifying analyses based on methodological design and quantified associations using fixed-effects meta-analysis models. We included 37 studies of 7,686 identified. Compared to reports in the literature as a whole, studies with population-based comparators showed weaker associations between migraine with aura and cryptogenic ischemic stroke in younger women (OR 1.4; 95% CI 0.9-2.0; 1 study), PFO and ischemic stroke (HR 1.6; 95 CI 1.0-2.5; 2 studies; OR 1.3; 95% CI 0.9-1.9; 3 studies), or PFO and migraine (OR 1.0; 95% CI 0.6-1.6; 1 study). It was not possible to look for interactions or effect modifiers. These results are limited by sources of bias within individual studies. The overall pairwise associations between PFO, cryptogenic ischemic stroke and migraine do not strongly suggest a causal role for PFO. Ongoing randomized trials of PFO closure may need larger numbers of participants to detect an overall beneficial effect. Copyright © 2012 S. Karger AG, Basel.

  7. Association between IGF2BP2 Polymorphisms and Type 2 Diabetes Mellitus: A Case–Control Study and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ping Rao

    2016-06-01

    Full Text Available Background: Genome-wide association studies (GWAS found that IGF2BP2 rs4402960 and rs1470579 polymorphisms were associated with type 2 diabetes mellitus (T2DM risk. Many studies have replicated this association, but yielded inconsistent results. Materials and Methods: A case-control study consisting of 461 T2DM patients and 434 health controls was conducted to detect the genetic susceptibility of IGF2BP2 in a northern Han Chinese population. A meta-analysis was to evaluate the association more precisely in Asians. Results: In the case-control study, the carriers of TT genotype at rs4402960 had a higher T2DM risk than the G carriers (TG + GG (adjusted odd ratio (AOR = 1.962, 95% confidence interval (95% CI = 1.065–3.612, p = 0.031]; CC carriers at rs1470579 were more susceptible to T2DM than A carriers (CA + AA (AOR = 2.014, 95% CI = 1.114–3.642, p = 0.021. The meta-analysis containing 36 studies demonstrated that the two polymorphisms were associated with T2DM under the allele comparison, genetic models of dominant and recessive in Asians (p < 0.05. The rs4402960 polymorphisms were significantly associated with the T2DM risk after stratification by diagnostic criterion, size of sample and average age and BMI of cases, while there’re no consistent results for rs1470579. Conclusions: Our data suggests that IGF2BP2 polymorphisms are associated with T2DM in Asian populations.

  8. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

    NARCIS (Netherlands)

    Springelkamp, Henriët; Höhn, René; Mishra, Aniket; Hysi, Pirro G; Khor, Chiea-Chuen; Loomis, Stephanie J; Bailey, Jessica N Cooke; Gibson, Jane; Thorleifsson, Gudmar; Janssen, Sarah F; Luo, Xiaoyan; Ramdas, Wishal D; Vithana, Eranga; Nongpiur, Monisha E; Montgomery, Grant W; Xu, Liang; Mountain, Jenny E; Gharahkhani, Puya; Lu, Yi; Amin, Najaf; Karssen, Lennart C; Sim, Kar-Seng; van Leeuwen, Elisabeth M; Iglesias, Adriana I; Verhoeven, Virginie J M; Hauser, Michael A; Loon, Seng-Chee; Despriet, Dominiek D G; Nag, Abhishek; Venturini, Cristina; Sanfilippo, Paul G; Schillert, Arne; Kang, Jae H; Landers, John; Jonasson, Fridbert; Cree, Angela J; van Koolwijk, Leonieke M E; Rivadeneira, Fernando; Souzeau, Emmanuelle; Jonsson, Vesteinn; Menon, Geeta; Weinreb, Robert N; de Jong, Paulus T V M; Oostra, Ben A; Uitterlinden, André G; Hofman, Albert; Ennis, Sarah; Thorsteinsdottir, Unnur; Burdon, Kathryn P; Spector, Timothy D; Mirshahi, Alireza; Saw, Seang-Mei; Vingerling, Johannes R; Teo, Yik-Ying; Haines, Jonathan L; Wolfs, Roger C W; Lemij, Hans G; Tai, E-Shyong; Jansonius, Nomdo M; Jonas, Jost B; Cheng, Ching-Yu; Aung, Tin; Viswanathan, Ananth C; Klaver, Caroline C W; Craig, Jamie E; Macgregor, Stuart; Mackey, David A; Lotery, Andrew J; Stefansson, Kari; Bergen, Arthur A B; Young, Terri L; Wiggs, Janey L; Pfeiffer, Norbert; Wong, Tien-Yin; Pasquale, Louis R; Hewitt, Alex W; van Duijn, Cornelia M; Hammond, Christopher J

    2014-01-01

    Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important

  9. GACT: a Genome build and Allele definition Conversion Tool for SNP imputation and meta-analysis in genetic association studies.

    Science.gov (United States)

    Sulovari, Arvis; Li, Dawei

    2014-07-19

    Genome-wide association studies (GWAS) have successfully identified genes associated with complex human diseases. Although much of the heritability remains unexplained, combining single nucleotide polymorphism (SNP) genotypes from multiple studies for meta-analysis will increase the statistical power to identify new disease-associated variants. Meta-analysis requires same allele definition (nomenclature) and genome build among individual studies. Similarly, imputation, commonly-used prior to meta-analysis, requires the same consistency. However, the genotypes from various GWAS are generated using different genotyping platforms, arrays or SNP-calling approaches, resulting in use of different genome builds and allele definitions. Incorrect assumptions of identical allele definition among combined GWAS lead to a large portion of discarded genotypes or incorrect association findings. There is no published tool that predicts and converts among all major allele definitions. In this study, we have developed a tool, GACT, which stands for Genome build and Allele definition Conversion Tool, that predicts and inter-converts between any of the common SNP allele definitions and between the major genome builds. In addition, we assessed several factors that may affect imputation quality, and our results indicated that inclusion of singletons in the reference had detrimental effects while ambiguous SNPs had no measurable effect. Unexpectedly, exclusion of genotypes with missing rate > 0.001 (40% of study SNPs) showed no significant decrease of imputation quality (even significantly higher when compared to the imputation with singletons in the reference), especially for rare SNPs. GACT is a new, powerful, and user-friendly tool with both command-line and interactive online versions that can accurately predict, and convert between any of the common allele definitions and between genome builds for genome-wide meta-analysis and imputation of genotypes from SNP-arrays or deep

  10. The Associations between VEGF Gene Polymorphisms and Diabetic Retinopathy Susceptibility: A Meta-Analysis of 11 Case-Control Studies

    Directory of Open Access Journals (Sweden)

    Liyuan Han

    2014-01-01

    Full Text Available Aims. Published data on the associations of VEGF polymorphisms with diabetic retinopathy (DR susceptibility are inconclusive. A systematic meta-analysis was undertaken to clarify this topic. Methods. Data were collected from the following electronic databases: PubMed, Embase, OVID, Web of Science, Elsevier Science Direct, Excerpta Medica Database (EMBASE, and Cochrane Library with the last report up to January 10, 2014. ORs and 95% CIs were calculated for VEGF–2578C/A (rs699947, –1154G/A (rs1570360, –460T/C (rs833061, −634G>C (rs2010963, and +936C/T (rs3025039 in at least two published studies. Meta-analysis was performed in a fixed/random effect model by using the software STATA 12.0. Results. A total of 11 studies fulfilling the inclusion criteria were included in this meta-analysis. A significant relationship between VEGF+936C/T (rs3025039 polymorphism and DR was found in a recessive model (OR = 3.19, 95% CI = 1.20–8.41, and P(z=0.01 in Asian and overall populations, while a significant association was also found between –460T/C (rs833061 polymorphism and DR risk under a recessive model (OR = 2.12, 95% CI = 1.12–4.01, and P(z=0.02. Conclusions. Our meta-analysis demonstrates that +936C/T (rs3025039 is likely to be associated with susceptibility to DR in Asian populations, and the recessive model of –460T/C (rs833061 is associated with elevated DR susceptibility.

  11. Association between depression and periodontitis: a systematic review and meta-analysis.

    Science.gov (United States)

    Araújo, Milena Moreira; Martins, Carolina Castro; Costa, Lidiane Cristina Machado; Cota, Luís Otávio Miranda; Faria, Rodrigo Lamounier Araújo Melo; Cunha, Fabiano Araújo; Costa, Fernando Oliveira

    2016-03-01

    The aim of this systematic review and meta-analysis was to assess the scientific evidence on the association between depression and periodontitis. An electronic search was conducted in three databases until October 2015 (PROSPERO-CRD42014006451). Hand searches and grey literature were also included. Search retrieved 423 potentially studies. Two independent reviewers selected the studies, extracted data and assessed risk bias through a modified version of Newcastle-Ottawa scale. Meta-analysis was performed for the presence/absence of periodontitis (dichotomic). Summary effect measures and odds ratio (OR) 95% CI were calculated. After selecting the studies, 15 were included in the systematic review (eight cross-sectional, six case-control and one cohort study). Six studies reported that depression was associated with periodontitis, whereas nine studies did not. The majority of studies had low risk of bias by methodological quality assessment. Meta-analysis of seven cross-sectional studies showed no significant association between depression and periodontitis (OR = 1.03, 95% CI = 0.75-1.41). Findings from the present systematic review showed a great heterogeneity among the studies and the summary effect measure of the meta-analysis cannot affirm an association between depression and periodontitis. Future studies with different designs in distinct populations should be conducted to investigate this association. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

    DEFF Research Database (Denmark)

    Macé, Aurélien; Tuke, Marcus A; Deelen, Patrick

    2017-01-01

    There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations......-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.......)). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m(2) for each Mb of total deletion burden (P = 2.5 × 10(-10), 6.0 × 10(-5), and 2.9 × 10(-3)). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor...

  13. SecureMA: protecting participant privacy in genetic association meta-analysis.

    Science.gov (United States)

    Xie, Wei; Kantarcioglu, Murat; Bush, William S; Crawford, Dana; Denny, Joshua C; Heatherly, Raymond; Malin, Bradley A

    2014-12-01

    Sharing genomic data is crucial to support scientific investigation such as genome-wide association studies. However, recent investigations suggest the privacy of the individual participants in these studies can be compromised, leading to serious concerns and consequences, such as overly restricted access to data. We introduce a novel cryptographic strategy to securely perform meta-analysis for genetic association studies in large consortia. Our methodology is useful for supporting joint studies among disparate data sites, where privacy or confidentiality is of concern. We validate our method using three multisite association studies. Our research shows that genetic associations can be analyzed efficiently and accurately across substudy sites, without leaking information on individual participants and site-level association summaries. Our software for secure meta-analysis of genetic association studies, SecureMA, is publicly available at http://github.com/XieConnect/SecureMA. Our customized secure computation framework is also publicly available at http://github.com/XieConnect/CircuitService. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Association between Hypertension and Epistaxis: Systematic Review and Meta-analysis.

    Science.gov (United States)

    Min, Hyun Jin; Kang, Hyun; Choi, Geun Joo; Kim, Kyung Soo

    2017-12-01

    Objective Whether there is an association or a cause-and-effect relationship between epistaxis and hypertension is a subject of longstanding controversy. The objective of this systematic review and meta-analysis was to determine the association between epistaxis and hypertension and to verify whether hypertension is an independent risk factor of epistaxis. Data Sources A comprehensive search was performed using the MEDLINE, EMBASE, and Cochrane Library databases. Review Methods The review was performed according to the Meta-analysis of Observational Studies in Epidemiology guidelines and reported using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Results We screened 2768 unique studies and selected 10 for this meta-analysis. Overall, the risk of epistaxis was significantly increased for patients with hypertension (odds ratio, 1.532 [95% confidence interval (CI), 1.181-1.986]; number needed to treat, 14.9 [95% CI, 12.3-19.0]). Results of the Q test and I 2 statistics suggested considerable heterogeneity ([Formula: see text] = 0.038, I 2 = 49.3%). The sensitivity analysis was performed by excluding 1 study at a time, and it revealed no change in statistical significance. Conclusion Although this meta-analysis had some limitations, our study demonstrated that hypertension was significantly associated with the risk of epistaxis. However, since this association does not support a causal relationship between hypertension and epistaxis, further clinical trials with large patient populations will be required to determine the impact of hypertension on epistaxis.

  15. FGWAS: Functional genome wide association analysis.

    Science.gov (United States)

    Huang, Chao; Thompson, Paul; Wang, Yalin; Yu, Yang; Zhang, Jingwen; Kong, Dehan; Colen, Rivka R; Knickmeyer, Rebecca C; Zhu, Hongtu

    2017-10-01

    Functional phenotypes (e.g., subcortical surface representation), which commonly arise in imaging genetic studies, have been used to detect putative genes for complexly inherited neuropsychiatric and neurodegenerative disorders. However, existing statistical methods largely ignore the functional features (e.g., functional smoothness and correlation). The aim of this paper is to develop a functional genome-wide association analysis (FGWAS) framework to efficiently carry out whole-genome analyses of functional phenotypes. FGWAS consists of three components: a multivariate varying coefficient model, a global sure independence screening procedure, and a test procedure. Compared with the standard multivariate regression model, the multivariate varying coefficient model explicitly models the functional features of functional phenotypes through the integration of smooth coefficient functions and functional principal component analysis. Statistically, compared with existing methods for genome-wide association studies (GWAS), FGWAS can substantially boost the detection power for discovering important genetic variants influencing brain structure and function. Simulation studies show that FGWAS outperforms existing GWAS methods for searching sparse signals in an extremely large search space, while controlling for the family-wise error rate. We have successfully applied FGWAS to large-scale analysis of data from the Alzheimer's Disease Neuroimaging Initiative for 708 subjects, 30,000 vertices on the left and right hippocampal surfaces, and 501,584 SNPs. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Association of Body Mass Index with Depression, Anxiety and Suicide-An Instrumental Variable Analysis of the HUNT Study.

    Directory of Open Access Journals (Sweden)

    Johan Håkon Bjørngaard

    Full Text Available While high body mass index is associated with an increased risk of depression and anxiety, cumulative evidence indicates that it is a protective factor for suicide. The associations from conventional observational studies of body mass index with mental health outcomes are likely to be influenced by reverse causality or confounding by ill-health. In the present study, we investigated the associations between offspring body mass index and parental anxiety, depression and suicide in order to avoid problems with reverse causality and confounding by ill-health.We used data from 32,457 mother-offspring and 27,753 father-offspring pairs from the Norwegian HUNT-study. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale and suicide death from national registers. Associations between offspring and own body mass index and symptoms of anxiety and depression and suicide mortality were estimated using logistic and Cox regression. Causal effect estimates were estimated with a two sample instrument variable approach using offspring body mass index as an instrument for parental body mass index.Both own and offspring body mass index were positively associated with depression, while the results did not indicate any substantial association between body mass index and anxiety. Although precision was low, suicide mortality was inversely associated with own body mass index and the results from the analysis using offspring body mass index supported these results. Adjusted odds ratios per standard deviation body mass index from the instrumental variable analysis were 1.22 (95% CI: 1.05, 1.43 for depression, 1.10 (95% CI: 0.95, 1.27 for anxiety, and the instrumental variable estimated hazard ratios for suicide was 0.69 (95% CI: 0.30, 1.63.The present study's results indicate that suicide mortality is inversely associated with body mass index. We also found support for a positive association between body mass index and depression, but not

  17. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes

    DEFF Research Database (Denmark)

    Ng, Maggie C Y; Shriner, Daniel; Chen, Brian H

    2014-01-01

    . In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs......) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications...... for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies....

  18. Meta-analysis for genome-wide association studies using case-control design: application and practice.

    Science.gov (United States)

    Shim, Sungryul; Kim, Jiyoung; Jung, Wonguen; Shin, In-Soo; Bae, Jong-Myon

    2016-01-01

    This review aimed to arrange the process of a systematic review of genome-wide association studies in order to practice and apply a genome-wide meta-analysis (GWMA). The process has a series of five steps: searching and selection, extraction of related information, evaluation of validity, meta-analysis by type of genetic model, and evaluation of heterogeneity. In contrast to intervention meta-analyses, GWMA has to evaluate the Hardy-Weinberg equilibrium (HWE) in the third step and conduct meta-analyses by five potential genetic models, including dominant, recessive, homozygote contrast, heterozygote contrast, and allelic contrast in the fourth step. The 'genhwcci' and 'metan' commands of STATA software evaluate the HWE and calculate a summary effect size, respectively. A meta-regression using the 'metareg' command of STATA should be conducted to evaluate related factors of heterogeneities.

  19. Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies

    Science.gov (United States)

    McKay, Gareth J.; Patterson, Chris C.; Chakravarthy, Usha; Dasari, Shilpa; Klaver, Caroline C.; Vingerling, Johannes R.; Ho, Lintje; de Jong, Paulus T.V.M.; Fletcher, Astrid E.; Young, Ian S.; Seland, Johan H.; Rahu, Mati; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vioque, Jesus; Hingorani, Aroon D.; Sofat, Reecha; Dean, Michael; Sawitzke, Julie; Seddon, Johanna M.; Peter, Inga; Webster, Andrew R.; Moore, Anthony T.; Yates, John R.W.; Cipriani, Valentina; Fritsche, Lars G.; Weber, Bernhard H.F.; Keilhauer, Claudia N.; Lotery, Andrew J.; Ennis, Sarah; Klein, Michael L.; Francis, Peter J.; Stambolian, Dwight; Orlin, Anton; Gorin, Michael B.; Weeks, Daniel E.; Kuo, Chia-Ling; Swaroop, Anand; Othman, Mohammad; Kanda, Atsuhiro; Chen, Wei; Abecasis, Goncalo R.; Wright, Alan F.; Hayward, Caroline; Baird, Paul N.; Guymer, Robyn H.; Attia, John; Thakkinstian, Ammarin; Silvestri, Giuliana

    2011-01-01

    Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status, has been reported. We present a pooled analysis (n=21,160) demonstrating associations between late AMD and APOε4 (OR=0.72 per haplotype; CI: 0.65–0.74; P=4.41×10−11) and APOε2 (OR=1.83 for homozygote carriers; CI: 1.04–3.23; P=0.04), following adjustment for age-group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR=1.54; CI: 1.38–1.72; P=2.8×10−15) and atrophic (OR=1.38; CI: 1.18–1.61; P=3.37×10−5) AMD but not early AMD (OR=0.94; CI: 0.86–1.03; P=0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyondε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology. PMID:21882290

  20. Tracheobronchomegaly associated tracheomalacia: analysis by sleep study.

    Science.gov (United States)

    Sundaram, P; Joshi, J M

    2004-01-01

    Tracheobronchomegaly (TBM) occasionally may progress to extensive tracheomalacia which leads to respiratory failure. Spirometry, dynamic expiratory multidetector computed tomography (CT), bronchoscopy are used to diagnose patients of suspected tracheobronchomalacia. We used the technique of night-time monitoring of respiratory variables to show the presence of respiratory abnormalities during sleep and which was corrected by applying nasal continuous positive airway pressure (CPAP). The study showed the presence of both apnoea and hypopnoeas, which were obstructive in nature with an apnoea-hypopnoea index (AHI) of 11, no snoring and associated oxygen desaturation of 75 per cent. A second overnight study with nasal continuous positive airway pressure at a critical pressure of 8 cm, the AHI decreased to 3 along with no drop in oxygen saturation. This non-invasive technique should be considered as a diagnostic tool in tracheobronchomalacia and to know the outcome of CPAP, surgical or stent therapy in this condition.

  1. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

    DEFF Research Database (Denmark)

    Cho, Yoon Shin; Chen, Chien-Hsiun; Hu, Cheng

    2012-01-01

    We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis...... (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3...

  2. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

    NARCIS (Netherlands)

    Macé, Aurélien; Tuke, Marcus A; Deelen, Patrick; Kristiansson, Kati; Mattsson, Hannele; Nõukas, Margit; Sapkota, Yadav; Schick, Ursula; Porcu, Eleonora; Rüeger, Sina; McDaid, Aaron F; Porteous, David; Winkler, Thomas W; Salvi, Erika; Shrine, Nick; Liu, Xueping; Ang, Wei Q; Zhang, Weihua; Feitosa, Mary F; Venturini, Cristina; van der Most, Peter J; Rosengren, Anders; Wood, Andrew R; Beaumont, Robin N; Jones, Samuel E; Ruth, Katherine S; Yaghootkar, Hanieh; Tyrrell, Jessica; Havulinna, Aki S; Boers, Harmen; Mägi, Reedik; Kriebel, Jennifer; Müller-Nurasyid, Martina; Perola, Markus; Nieminen, Markku; Lokki, Marja-Liisa; Kähönen, Mika; Viikari, Jorma S; Geller, Frank; Lahti, Jari; Palotie, Aarno; Koponen, Päivikki; Lundqvist, Annamari; Rissanen, Harri; Bottinger, Erwin P; Afaq, Saima; Wojczynski, Mary K; Lenzini, Petra; Nolte, Ilja M; Sparsø, Thomas; Schupf, Nicole; Christensen, Kaare; Perls, Thomas T; Newman, Anne B; Werge, Thomas; Snieder, Harold; Spector, Timothy D; Chambers, John C; Koskinen, Seppo; Melbye, Mads; Raitakari, Olli T; Lehtimäki, Terho; Tobin, Martin D; Wain, Louise V; Sinisalo, Juha; Peters, Annette; Meitinger, Thomas; Martin, Nicholas G; Wray, Naomi R; Montgomery, Grant W; Medland, Sarah E; Swertz, Morris A; Vartiainen, Erkki; Borodulin, Katja; Männistö, Satu; Murray, Anna; Bochud, Murielle; Jacquemont, Sébastien; Rivadeneira, Fernando; Hansen, Thomas F; Oldehinkel, Albertine J; Mangino, Massimo; Province, Michael A; Deloukas, Panos; Kooner, Jaspal S; Freathy, Rachel M; Pennell, Craig; Feenstra, Bjarke; Strachan, David P; Lettre, Guillaume; Hirschhorn, Joel; Cusi, Daniele; Heid, Iris M; Hayward, Caroline; Männik, Katrin; Beckmann, Jacques S; Loos, Ruth J F; Nyholt, Dale R; Metspalu, Andres; Eriksson, Johan G; Weedon, Michael N; Salomaa, Veikko; Franke, Lude; Reymond, Alexandre; Frayling, Timothy M; Kutalik, Zoltán

    2017-01-01

    There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at

  3. Association Analysis in Rice: From Application to Utilization

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    2016-08-01

    Full Text Available Association analysis based on linkage disequilibrium (LD is an efficient way to dissect complex traits and to identify gene functions in rice. Although association analysis is an effective way to construct fine maps for quantitative traits, there are a few issues which need to be addressed. In this review, we will first summarize type, structure and LD level of populations used for association analysis of rice, and then discuss the genotyping methods and statistical approaches used for association analysis in rice. Moreover, we will review current shortcomings and benefits of association analysis as well as specific types of future research to overcome these shortcomings. Furthermore, we will analyze the reasons for the underutilization of the results within association analysis in rice breeding.

  4. Meta-Analysis of Associations Between Interleukin-10 Polymorphisms and Susceptibility to Vasculitis.

    Science.gov (United States)

    Jung, Jae Hyun; Song, Gwan Gyu; Lee, Young Ho

    2015-01-01

    This study determined whether interleukin-10 (IL-10) polymorphisms are associated with susceptibility to vasculitis. A meta-analysis was conducted of the associations between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and vasculitis. A total of 21 comparative studies involving 4121 patients and 5504 controls were considered in the meta-analysis. Meta-analysis revealed no association between the IL-10-1082 G allele and vasculitis in all study subjects (OR = 0.927, 95% CI = 0.780-1.102, p = 0.389). However, disease-specific meta-analysis showed an association between Wegener's granulomatosis (WG) and the IL-10-1082 G allele (OR = 0.729, 95% CI = 0.547-0.971, p = 0.031). Meta-analysis revealed an association between vasculitis and the IL-10-819 C allele (OR = 0.804, 95% CI = 0.706-0.916, p = 0.001) in all study subjects and Behcet's disease (BD) (OR = 0.724, 95% CI = 0.679-0.781, p vasculitis in all study subjects (OR = 0.805, 95% CI = 0.619-0.938, p = 0.005) and BD (OR = 0.718, 95% CI = 0.661-0.781, p vasculitis in Europeans (OR = 1.239, 95% CI = 1.105-1.513, p = 0.035). This meta-analysis showed that IL-10 polymorphisms are associated with vasculitis susceptibility, especially in WG and BD.

  5. Meta-analysis for genome-wide association studies using case-control design: application and practice

    Directory of Open Access Journals (Sweden)

    Sungryul Shim

    2016-12-01

    Full Text Available This review aimed to arrange the process of a systematic review of genome-wide association studies in order to practice and apply a genome-wide meta-analysis (GWMA. The process has a series of five steps: searching and selection, extraction of related information, evaluation of validity, meta-analysis by type of genetic model, and evaluation of heterogeneity. In contrast to intervention meta-analyses, GWMA has to evaluate the Hardy–Weinberg equilibrium (HWE in the third step and conduct meta-analyses by five potential genetic models, including dominant, recessive, homozygote contrast, heterozygote contrast, and allelic contrast in the fourth step. The ‘genhwcci’ and ‘metan’ commands of STATA software evaluate the HWE and calculate a summary effect size, respectively. A meta-regression using the ‘metareg’ command of STATA should be conducted to evaluate related factors of heterogeneities.

  6. Association between tea consumption and osteoporosis: A meta-analysis.

    Science.gov (United States)

    Sun, Kang; Wang, Le; Ma, Qingping; Cui, Qiaoyun; Lv, Qianru; Zhang, Wenzheng; Li, Xinghui

    2017-12-01

    Previous reports have suggested a potential association of tea consumption with the risk of osteoporosis. As such association is controversial, we conducted a meta-analysis to assess the relationship between tea consumption and osteoporosis. We systematically searched PubMed, EMBASE and WanFang databases until March 30, 2016, using the keywords "tea and osteoporosis," without limits of language. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived by using random-effects models throughout the analyses. We conducted the analysis of the statistical heterogeneity using Cochrane I. The funnel plot was used to speculate the publication bias, while the subgroup analysis and multiround elimination method were employed. Our study was based on 17 journal articles, including 2 prospective cohort studies, 4 case-control studies, and 11 cross-sectional studies. In the present study, the total OR of osteoporosis for the highest versus the lowest categories of tea consumption was 0.62 (95% CI, 0.46-0.83), with significant heterogeneity among studies (I = 94%, P tea consumption and osteoporosis. Subgroup analysis showed that tea consumption could reduce the risk of osteoporosis in all examined subgroups. In the present study, it can be concluded from the results that tea consumption can reduce the risk of osteoporosis.

  7. Fontan-associated protein-losing enteropathy and heart transplant: A Pediatric Heart Transplant Study analysis.

    Science.gov (United States)

    Schumacher, Kurt R; Gossett, Jeffrey; Guleserian, Kristine; Naftel, David C; Pruitt, Elizabeth; Dodd, Debra; Carboni, Michael; Lamour, Jacqueline; Pophal, Stephen; Zamberlan, Mary; Gajarski, Robert J

    2015-09-01

    Post-Fontan protein-losing enteropathy (PLE) is associated with significant morbidity and mortality. Although heart transplantation (HTx) can be curative, PLE may increase the risk of morbidity before and after HTx. This study analyzed the influence of PLE influence on waiting list and post-HTx outcomes in a pediatric cohort. Fontan patients listed for HTx and enrolled in the Pediatric Heart Transplant Study from 1999 to 2012 were stratified by a diagnosis of PLE, and the association of PLE with waiting list and post-HTx mortality, rejection, and infection was analyzed. Compared with non-PLE Fontan patients (n = 260), PLE patients listed for HTx (n = 96) were older (11.9 years vs 7.6 years; p = 0.003), had a larger body surface area (1.1 m(2) vs 0.9 m(2); p = 0.0001), had lower serum bilirubin (0.5 vs 0.9 mg/dl; p = 0.01), lower B-type natriuretic peptide (59 vs 227 pg/ml; p = 0.006), and were less likely to be on a ventilator (3% vs 13%; p = 0.006). PLE patients had lower waiting list mortality than non-PLE Fontan patients (p PLE was not independently associated with increased post-HTx mortality at any time point. In this multicenter cohort, the diagnosis of PLE alone was not associated with increased waiting list mortality or post-HTx morbidity or mortality. Given the limitations of our data, this analysis suggests that PLE patients in the pediatric age group have outcomes similar to their non-PLE counterparts. Additional multicenter studies of PLE patients with targeted collection of PLE-specific information will be necessary to fully delineate the risks conferred by PLE for HTx. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  8. PERSPECTIVES OF FACTORIAL ANALYSIS IN STUDYING ASSOCIATIONS BETWEEN IMMUNE SYSTEM PARAMETERS AND CLINICAL CHARACTERISTICS IN GASTRIC CANCER

    Directory of Open Access Journals (Sweden)

    I. G. Solovyeva

    2010-01-01

    Full Text Available When studying functional features of immune system, a lot of quantitative and functional parameters are determined. A multifactorial analysis allows of detecting interdependent immunological parameters and defining them as significant factors. In present study, four factors are revealed, which are associated with certain clinical characteristics of gastric cancer (tumor invasion depth, lymph node status and distant metastases, tumor stage, histological type. The data obtained are of interest, with regard of systemic approach to functional studies of immune functions.

  9. Early subsidence of shape-closed hip arthroplasty stems is associated with late revision. A systematic review and meta-analysis of 24 RSA studies and 56 survival studies.

    Science.gov (United States)

    van der Voort, Paul; Pijls, Bart G; Nieuwenhuijse, Marc J; Jasper, Jorrit; Fiocco, Marta; Plevier, Josepha W M; Middeldorp, Saskia; Valstar, Edward R; Nelissen, Rob G H H

    2015-01-01

    Few studies have addressed the association between early migration of femoral stems and late aseptic revision in total hip arthroplasty. We performed a meta-regression analysis on 2 parallel systematic reviews and meta-analyses to determine the association between early migration and late aseptic revision of femoral stems. Of the 2 reviews, one covered early migration data obtained from radiostereometric analysis (RSA) studies and the other covered long-term aseptic revision rates obtained from survival studies with endpoint revision for aseptic loosening. Stems were stratified according to the design concept: cemented shape-closed, cemented force-closed, and uncemented. A weighted regression model was used to assess the association between early migration and late aseptic revision, and to correct for confounders. Thresholds for acceptable and unacceptable migration were determined in accordance with the national joint registries (≤ 5% revision at 10 years) and the NICE criteria (≤ 10% revision at 10 years). 24 studies (731 stems) were included in the RSA review and 56 studies (20,599 stems) were included in the survival analysis review. Combining both reviews for the 3 design concepts showed that for every 0.1-mm increase in 2-year subsidence, as measured with RSA, there was a 4% increase in revision rate for the shape-closed stem designs. This association remained after correction for age, sex, diagnosis, hospital type, continent, and study quality. The threshold for acceptable migration of shape-closed designs was defined at 0.15 mm; stems subsiding less than 0.15 mm in 2 years had revision rates of less than 5% at 10 years, while stems exceeding 0.15 mm subsidence had revision rates of more than 5%. There was a clinically relevant association between early subsidence of shape-closed femoral stems and late revision for aseptic loosening. This association can be used to assess the safety of shape-closed stem designs. The published research is not sufficient

  10. Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: The DAMAGE study

    DEFF Research Database (Denmark)

    Reiling, Erwin; van Vliet-Ostaptchouk, Jana V; van 't Riet, Esther

    2009-01-01

    ). After a meta-analysis, only one SNP in SIRT4 (rs2522138) remained significant (P=0.01). Extending the second stage with samples from the Danish Steno Study (n=1220 participants) resulted in a common odds ratio (OR) of 0.92 (0.85-1.00), P=0.06. Moreover, in a large meta-analysis of three genome......Mitochondria play an important role in many processes, like glucose metabolism, fatty acid oxidation and ATP synthesis. In this study, we aimed to identify association of common polymorphisms in nuclear-encoded genes involved in mitochondrial protein synthesis and biogenesis with type II diabetes...

  11. Association between particulate matter 2.5 and diabetes mellitus: A meta-analysis of cohort studies.

    Science.gov (United States)

    He, Dian; Wu, Shaowen; Zhao, Haiping; Qiu, Hongyan; Fu, Yang; Li, Xingming; He, Yan

    2017-09-01

    The present meta-analysis was carried out to assess the association between exposure to the level of atmospheric particulate matter 2.5 (PM2.5; fine particulate matter with aerodynamic diameter less than 2.5 μm) and type 2 diabetes mellitus or gestational diabetes mellitus (GDM). We searched the Medline, EMBASE, Cochrane and Web of Science databases to obtain articles according to the responding literature search strategies. Among a total of 279 identified articles, 55 were reviewed in depth, of which 10 articles (11 cohort studies) satisfied the inclusion criteria. Only cohort studies that disclosed the association between PM2.5 and type 2 diabetes mellitus or GDM were included in this article. A fixed-effects model was selected if P > 0.1 and I 2 diabetes mellitus (type 2 diabetes mellitus and GDM). The relative risk was used to estimate the association between PM2.5 and diabetes mellitus. The positive associations between PM2.5 and the incidence of type 2 diabetes mellitus were found in the long-term exposure period (relative risk 1.25, 95% confidence interval 1.10-1.43), which showed that with every 10-μg/m 3 increase in PM2.5, the risk of type 2 diabetes mellitus would increase by 25% in the long-term exposure. Although the significant associations were not identified between maternal exposure to PM2.5 and GDM in the first trimester, the second trimester and the entire pregnancy periods, we could conclude that maternal exposure to PM2.5 in the entire pregnancy period would be more likely to lead to developing GDM (relative risk 1.162, 95% confidence interval 0.806-1.675) than the other two periods. Long-term exposure to PM2.5 would be more likely to lead to developing type 2 diabetes mellitus, but more studies would be required to confirm the association between PM2.5 and GDM. It might be a wise to take effective measures to reduce PM2.5 exposure in vulnerable populations, especially for pregnant women. © 2017 The Authors. Journal of Diabetes Investigation

  12. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    Science.gov (United States)

    Berndt, Sonja I.; Camp, Nicola J.; Skibola, Christine F.; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S.; Smedby, Karin E.; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S.; Lan, Qing; Teras, Lauren R.; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R.; Hartge, Patricia; Purdue, Mark P.; Birmann, Brenda M.; Vajdic, Claire M.; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G.; Shanafelt, Tait D.; Novak, Anne J.; Kay, Neil E.; Liebow, Mark; Cunningham, Julie M.; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T.; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A.; Diver, W Ryan; Link, Brian K.; Weiner, George J.; Conde, Lucia; Bracci, Paige M.; Riby, Jacques; Arnett, Donna K.; Zhi, Degui; Leach, Justin M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G.; Achenbach, Sara J.; Vachon, Celine M.; Goldin, Lynn R.; Strom, Sara S.; Leis, Jose F.; Weinberg, J. Brice; Caporaso, Neil E.; Norman, Aaron D.; De Roos, Anneclaire J.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María- Dolores; Vermeulen, Roel C. H.; Travis, Ruth C.; Southey, Melissa C.; Milne, Roger L.; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R.; Villano, Danylo J.; Maria, Ann; Spinelli, John J.; Gascoyne, Randy D.; Connors, Joseph M.; Bertrand, Kimberly A.; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M.; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E.; Snowden, John A.; Wright, Josh; Fraumeni, Joseph F.; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R.; Chanock, Stephen J.; Rothman, Nathaniel; Slager, Susan L.

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10−8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10−7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility. PMID:26956414

  13. Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations

    NARCIS (Netherlands)

    C.M. O'Seaghdha (Conall); H. Wu (Hongsheng); Q. Yang (Qiong); K. Kapur (Karen); I. Guessous (Idris); P. Zuber (Patrick); A. Köttgen (Anna); C. Stoudmann (Candice); A. Teumer (Alexander); Z. Kutalik (Zoltán); M. Mangino (Massimo); A. Dehghan (Abbas); W. Zhang (Weihua); G. Eiriksdottir (Gudny); G. Li (Guo); T. Tanaka (Toshiko); L. Portas (Laura); L.M. Lopez (Lorna); C. Hayward (Caroline); K. Lohman (Kurt); K. Matsuda (Koichi); S. Padmanabhan (Sandosh); D. Firsov (Dmitri); R. Sorice; S. Ulivi (Shelia); A.C. Brockhaus (A. Catharina); M.E. Kleber (Marcus); A. Mahajan (Anubha); F.D.J. Ernst (Florian); V. Gudnason (Vilmundur); L.J. Launer (Lenore); A. Mace (Aurelien); E.A. Boerwinkle (Eric); D.E. Arking (Dan); C. Tanikawa (Chizu); Y. Nakamura (Yusuke); M.J. Brown (Morris); J.-M. Gaspoz (Jean-Michel); J.-M. Theler (Jean-Marc); D.S. Siscovick (David); B.M. Psaty (Bruce); S.M. Bergmann (Sven); P. Vollenweider (Peter); V. Vitart (Veronique); A.F. Wright (Alan); T. Zemunik (Tatijana); M. Boban (Mladen); I. Kolcic (Ivana); P. Navarro (Pau); E.M. Brown (Edward); K. Estrada Gil (Karol); J. Ding (Jingzhong); T.B. Harris (Tamara); S. Bandinelli (Stefania); D.G. Hernandez (Dena); A. Singleton (Andrew); S. Girotto; D. Ruggiero; P. d' Adamo (Pio); A. Robino (Antonietta); T. Meitinger (Thomas); C. Meisinger (Christa); G. Davies (Gail); J.M. Starr (John); J.C. Chambers (John); B.O. Boehm (Bernhard); B. Winkelmann; J. Huang (Jian); D. Murgia (Daniela); S.H. Wild (Sarah); H. Campbell (Harry); A.D. Morris (Andrew); O.H. Franco (Oscar); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); U. Vol̈ker (Uwe); M. Hannemann (Mario); R. Biffar (Reiner); W. Hoffmann (Wolfgang); S.-Y. Shin; P. Lescuyer (Pierre); H. Henry (Hughes); C. Schurmann (Claudia); P. Munroe (Patricia); P. Gasparini (Paolo); N. Pirastu (Nicola); M. Ciullo; C. Gieger (Christian); W. März (Winfried); L. Lind (Lars); T.D. Spector (Timothy); G.D. Smith; I. Rudan (Igor); J.F. Wilson (James); O. Polasek (Ozren); I.J. Deary (Ian); M. Pirastu (Mario); L. Ferrucci (Luigi); Y. Liu (YongMei); B. Kestenbaum (Bryan); J.S. Kooner (Jaspal); J.C.M. Witteman (Jacqueline); M. Nauck (Matthias); W.H.L. Kao (Wen); H. Wallaschofski (Henri); O. Bonny (Olivier); C. Fox (Craig); M. Bochud (Murielle)

    2013-01-01

    textabstractCalcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17

  14. Association Between Consumption of Fruits and Vegetables and Risk of Colorectal Adenoma: A PRISMA-Compliant Meta-Analysis of Observational Studies.

    Science.gov (United States)

    Ben, Qiwen; Zhong, Jie; Liu, Jun; Wang, Lifu; Sun, Yunwei; Yv, Lifen; Yuan, Yaozong

    2015-10-01

    There have been contradictory results about the association of fruits and vegetables intake with colorectal adenoma (CRA) risk, the precursor lesion of colorectal cancer. Herein, we have conducted a meta-analysis of the published observational studies to have a clear understanding about this association.Eligible studies up to November 30, 2014, were identified and retrieved by searching MEDLINE and EMBASE databases along with the manual review of the reference list of the retrieved studies. The quality of the included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale, and random-effects model was used to calculate summary relative risk (SRR) and corresponding 95% confidence interval (CI).A total of 22 studies involving 11,696 CRA subjects were part of this meta-analysis. The SRR for the highest versus the lowest intake of vegetables alone was 0.91 (95% CI: 0.80-1.02, Pheterogeneity = 0.025), whereas for vegetables and fruits combined, it was 0.82 (95% CI: 0.75-0.91, Pheterogeneity = 0.369), and for fruits alone, it was 0.79 (95% CI: 0.71-0.88, Pheterogeneity = 0.111). In addition, linear dose-response analysis also showed similar results, for example, for per 100 g/d increment of fruits, the SRR was 0.94 (95% CI: 0.92-0.97) and for vegetables it was 0.98 (95% CI: 0.96-1.01). Nonlinear association was only observed for vegetables (Pnonlinearity = 0.024), but not for fruits (Pnonlinearity = 0.583).Thus, this meta-analysis suggested that fruits consumption have a significant protective effect on CRA risk, but not vegetables. Moreover, we recommend additional studies with prospective designs that use validated questionnaires and control for important confounders to further validate the overall results.

  15. Landscape of dietary factors associated with risk of gastric cancer: A systematic review and dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Fang, Xuexian; Wei, Jiayu; He, Xuyan; An, Peng; Wang, Hao; Jiang, Li; Shao, Dandan; Liang, Han; Li, Yi; Wang, Fudi; Min, Junxia

    2015-12-01

    The associations between dietary factors and gastric cancer risk have been analysed by many studies, but with inconclusive results. We conducted a meta-analysis of prospective studies to systematically investigate the associations. Relevant studies were identified through searching Medline, Embase, and Web of Science up to June 30, 2015. We included prospective cohort studies of intake of dietary factors with risk estimates and 95% confidence intervals for gastric cancer. Seventy-six prospective cohort studies were eligible and included in the analysis. We ascertained 32,758 gastric cancer cases out of 6,316,385 participants in relations to intake of 67 dietary factors, covering a wide ranging of vegetables, fruit, meat, fish, salt, alcohol, tea, coffee, and nutrients, during 3.3 to 30 years of follow-up. Evidence from this study indicates that consumption of total fruit and white vegetables, but not total vegetables, was inversely associated with gastric cancer risk. Both fruit and white vegetables are rich sources of vitamin C, which showed significant protective effect against gastric cancer by our analysis too. Furthermore, we found concordant positive associations between high-salt foods and gastric cancer risk. In addition, a strong effect of alcohol consumption, particularly beer and liquor but not wine, on gastric cancer risk was observed compared with nondrinkers. Dose-response analysis indicated that risk of gastric cancer was increased by 12% per 5 g/day increment of dietary salt intake or 5% per 10 g/day increment of alcohol consumption, and that a 100 g/day increment of fruit consumption was inversely associated with 5% reduction of risk. This study provides comprehensive and strong evidence that there are a number of protective and risk factors for gastric cancer in diet. Our findings may have significant public health implications with regard to prevention of gastric cancer and provide insights into future cohort studies and the design of related

  16. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Maggie C Y Ng

    2014-08-01

    Full Text Available Type 2 diabetes (T2D is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1 and two novel loci (HLA-B and INS-IGF2 at genome-wide significance (4.15 × 10(-94association (2.2 × 10(-23 < locus-wide P<0.05. These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.

  17. Meta-analysis of epigenome-wide association studies of cognitive abilities.

    Science.gov (United States)

    Marioni, Riccardo E; McRae, Allan F; Bressler, Jan; Colicino, Elena; Hannon, Eilis; Li, Shuo; Prada, Diddier; Smith, Jennifer A; Trevisi, Letizia; Tsai, Pei-Chien; Vojinovic, Dina; Simino, Jeannette; Levy, Daniel; Liu, Chunyu; Mendelson, Michael; Satizabal, Claudia L; Yang, Qiong; Jhun, Min A; Kardia, Sharon L R; Zhao, Wei; Bandinelli, Stefania; Ferrucci, Luigi; Hernandez, Dena G; Singleton, Andrew B; Harris, Sarah E; Starr, John M; Kiel, Douglas P; McLean, Robert R; Just, Allan C; Schwartz, Joel; Spiro, Avron; Vokonas, Pantel; Amin, Najaf; Ikram, M Arfan; Uitterlinden, Andre G; van Meurs, Joyce B J; Spector, Tim D; Steves, Claire; Baccarelli, Andrea A; Bell, Jordana T; van Duijn, Cornelia M; Fornage, Myriam; Hsu, Yi-Hsiang; Mill, Jonathan; Mosley, Thomas H; Seshadri, Sudha; Deary, Ian J

    2018-01-08

    Cognitive functions are important correlates of health outcomes across the life-course. Individual differences in cognitive functions are partly heritable. Epigenetic modifications, such as DNA methylation, are susceptible to both genetic and environmental factors and may provide insights into individual differences in cognitive functions. Epigenome-wide meta-analyses for blood-based DNA methylation levels at ~420,000 CpG sites were performed for seven measures of cognitive functioning using data from 11 cohorts. CpGs that passed a Bonferroni correction, adjusting for the number of CpGs and cognitive tests, were assessed for: longitudinal change; being under genetic control (methylation QTLs); and associations with brain health (structural MRI), brain methylation and Alzheimer's disease pathology. Across the seven measures of cognitive functioning (meta-analysis n range: 2557-6809), there were epigenome-wide significant (P cognitive function (cg21450381, P = 1.6 × 10 -8 ), and phonemic verbal fluency (cg12507869, P = 2.5 × 10 -9 ). The CpGs are located in an intergenic region on chromosome 12 and the INPP5A gene on chromosome 10, respectively. Both probes have moderate correlations (~0.4) with brain methylation in Brodmann area 20 (ventral temporal cortex). Neither probe showed evidence of longitudinal change in late-life or associations with white matter brain MRI measures in one cohort with these data. A methylation QTL analysis suggested that rs113565688 was a cis methylation QTL for cg12507869 (P = 5 × 10 -5 and 4 × 10 -13 in two lookup cohorts). We demonstrate a link between blood-based DNA methylation and measures of phonemic verbal fluency and global cognitive ability. Further research is warranted to understand the mechanisms linking genomic regulatory changes with cognitive function to health and disease.

  18. A mega-analysis of genome-wide association studies for major depressive disorder.

    Science.gov (United States)

    Ripke, Stephan; Wray, Naomi R; Lewis, Cathryn M; Hamilton, Steven P; Weissman, Myrna M; Breen, Gerome; Byrne, Enda M; Blackwood, Douglas H R; Boomsma, Dorret I; Cichon, Sven; Heath, Andrew C; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A F; Martin, Nicholas G; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M; Penninx, Brenda P; Pergadia, Michele L; Potash, James B; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H; Preisig, Martin; Smoller, Jordan W; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R; Bettecken, Thomas; Binder, Elisabeth B; Breuer, René; Castro, Victor M; Churchill, Susanne E; Coryell, William H; Craddock, Nick; Craig, Ian W; Czamara, Darina; De Geus, Eco J; Degenhardt, Franziska; Farmer, Anne E; Fava, Maurizio; Frank, Josef; Gainer, Vivian S; Gallagher, Patience J; Gordon, Scott D; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A; Kohane, Isaac S; Kohli, Martin A; Korszun, Ania; Landen, Mikael; Lawson, William B; Lewis, Glyn; Macintyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M; Middleton, Lefkos; Montgomery, Grant M; Murphy, Shawn N; Nauck, Matthias; Nolen, Willem A; Nyholt, Dale R; O'Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A; Schulz, Andrea; Schulze, Thomas G; Shyn, Stanley I; Sigurdsson, Engilbert; Slager, Susan L; Smit, Johannes H; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B; Willemsen, Gonneke; Zitman, Frans G; Neale, Benjamin; Daly, Mark; Levinson, Douglas F; Sullivan, Patrick F

    2013-04-01

    Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.

  19. Gene set analysis for interpreting genetic studies

    DEFF Research Database (Denmark)

    Pers, Tune H

    2016-01-01

    Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways...

  20. GWATCH: a web platform for automated gene association discovery analysis

    Science.gov (United States)

    2014-01-01

    Background As genome-wide sequence analyses for complex human disease determinants are expanding, it is increasingly necessary to develop strategies to promote discovery and validation of potential disease-gene associations. Findings Here we present a dynamic web-based platform – GWATCH – that automates and facilitates four steps in genetic epidemiological discovery: 1) Rapid gene association search and discovery analysis of large genome-wide datasets; 2) Expanded visual display of gene associations for genome-wide variants (SNPs, indels, CNVs), including Manhattan plots, 2D and 3D snapshots of any gene region, and a dynamic genome browser illustrating gene association chromosomal regions; 3) Real-time validation/replication of candidate or putative genes suggested from other sources, limiting Bonferroni genome-wide association study (GWAS) penalties; 4) Open data release and sharing by eliminating privacy constraints (The National Human Genome Research Institute (NHGRI) Institutional Review Board (IRB), informed consent, The Health Insurance Portability and Accountability Act (HIPAA) of 1996 etc.) on unabridged results, which allows for open access comparative and meta-analysis. Conclusions GWATCH is suitable for both GWAS and whole genome sequence association datasets. We illustrate the utility of GWATCH with three large genome-wide association studies for HIV-AIDS resistance genes screened in large multicenter cohorts; however, association datasets from any study can be uploaded and analyzed by GWATCH. PMID:25374661

  1. Intersubject synchronisation analysis of brain activity associated with the instant effects of acupuncture: an fMRI study.

    Science.gov (United States)

    Jin, Lingmin; Sun, Jinbo; Xu, Ziliang; Yang, Xuejuan; Liu, Peng; Qin, Wei

    2018-02-01

    To use a promising analytical method, namely intersubject synchronisation (ISS), to evaluate the brain activity associated with the instant effects of acupuncture and compare the findings with traditional general linear model (GLM) methods. 30 healthy volunteers were recruited for this study. Block-designed manual acupuncture stimuli were delivered at SP6, and de qi sensations were measured after acupuncture stimulation. All subjects underwent functional MRI (fMRI) scanning during the acupuncture stimuli. The fMRI data were separately analysed by ISS and traditional GLM methods. All subjects experienced de qi sensations. ISS analysis showed that the regions activated during acupuncture stimulation at SP6 were mainly divided into five clusters based on the time courses. The time courses of clusters 1 and 2 were in line with the acupuncture stimulation pattern, and the active regions were mainly involved in the sensorimotor system and salience network. Clusters 3, 4 and 5 displayed an almost contrary time course relative to the stimulation pattern. The brain regions activated included the default mode network, descending pain modulation pathway and visual cortices. GLM analysis indicated that the brain responses associated with the instant effects of acupuncture were largely implicated in sensory and motor processing and sensory integration. The ISS analysis considered the sustained effect of acupuncture and uncovered additional information not shown by GLM analysis. We suggest that ISS may be a suitable approach to investigate the brain responses associated with the instant effects of acupuncture. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.

    Science.gov (United States)

    de Boer, Ynto S; van Gerven, Nicole M F; Zwiers, Antonie; Verwer, Bart J; van Hoek, Bart; van Erpecum, Karel J; Beuers, Ulrich; van Buuren, Henk R; Drenth, Joost P H; den Ouden, Jannie W; Verdonk, Robert C; Koek, Ger H; Brouwer, Johannes T; Guichelaar, Maureen M J; Vrolijk, Jan M; Kraal, Georg; Mulder, Chris J J; van Nieuwkerk, Carin M J; Fischer, Janett; Berg, Thomas; Stickel, Felix; Sarrazin, Christoph; Schramm, Christoph; Lohse, Ansgar W; Weiler-Normann, Christina; Lerch, Markus M; Nauck, Matthias; Völzke, Henry; Homuth, Georg; Bloemena, Elisabeth; Verspaget, Hein W; Kumar, Vinod; Zhernakova, Alexandra; Wijmenga, Cisca; Franke, Lude; Bouma, Gerd

    2014-08-01

    Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits. In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

    NARCIS (Netherlands)

    C.E. Elks (Cathy); J.R.B. Perry (John); P. Sulem (Patrick); D.I. Chasman (Daniel); N. Franceschini (Nora); C. He (Chunyan); K.L. Lunetta (Kathryn); J.A. Visser (Jenny); E.M. Byrne (Enda); D.L. Cousminer (Diana); D.F. Gudbjartsson (Daniel); T. Esko (Tõnu); B. Feenstra (Bjarke); J.J. Hottenga (Jouke Jan); D.L. Koller (Daniel); Z. Kutalik (Zoltán); P. Lin (Peng); M. Mangino (Massimo); M. Marongiu (Mara); P.F. McArdle (Patrick); A.V. Smith (Albert Vernon); L. Stolk (Lisette); S. van Wingerden (Sophie); J.H. Zhao (Jing Hua); E. Albrecht (Eva); T. Corre (Tanguy); E. Ingelsson (Erik); C. Hayward (Caroline); P.K. Magnusson (Patrik); S. Ulivi (Shelia); N.M. Warrington (Nicole); L. Zgaga (Lina); H. Alavere (Helene); N. Amin (Najaf); T. Aspelund (Thor); S. Bandinelli (Stefania); I.E. Barroso (Inês); G. Berenson (Gerald); S.M. Bergmann (Sven); H. Blackburn (Hannah); E.A. Boerwinkle (Eric); J.E. Buring (Julie); F. Busonero; H. Campbell (Harry); S.J. Chanock (Stephen); W. Chen (Wei); M. Cornelis (Marilyn); D.J. Couper (David); A.D. Coviello (Andrea); P. d' Adamo (Pio); U. de Faire (Ulf); E.J.C. de Geus (Eco); P. Deloukas (Panagiotis); A. Döring (Angela); D.F. Easton (Douglas); G. Eiriksdottir (Gudny); V. Emilsson (Valur); J.G. Eriksson (Johan); L. Ferrucci (Luigi); A.R. Folsom (Aaron); T. Foroud (Tatiana); M. Garcia (Melissa); P. Gasparini (Paolo); F. Geller (Frank); C. Gieger (Christian); V. Gudnason (Vilmundur); A.S. Hall (Alistair); S.E. Hankinson (Susan); L. Ferreli (Liana); A.C. Heath (Andrew); D.G. Hernandez (Dena); A. Hofman (Albert); F.B. Hu (Frank); T. Illig (Thomas); M.R. Järvelin; A.D. Johnson (Andrew); D. Karasik (David); K-T. Khaw (Kay-Tee); D.P. Kiel (Douglas); T.O. Kilpelänen (Tuomas); I. Kolcic (Ivana); P. Kraft (Peter); L.J. Launer (Lenore); J.S.E. Laven (Joop); S. Li (Shengxu); J. Liu (Jianjun); D. Levy (Daniel); N.G. Martin (Nicholas); M. Melbye (Mads); V. Mooser (Vincent); J.C. Murray (Jeffrey); M.A. Nalls (Michael); P. Navarro (Pau); M. Nelis (Mari); A.R. Ness (Andrew); K. Northstone (Kate); B.A. Oostra (Ben); M. Peacock (Munro); C. Palmer (Cameron); A. Palotie (Aarno); G. Paré (Guillaume); A.N. Parker (Alex); N.L. Pedersen (Nancy); L. Peltonen (Leena Johanna); C.E. Pennell (Craig); P.D.P. Pharoah (Paul); O. Polasek (Ozren); A.S. Plump (Andrew); A. Pouta (Anneli); E. Porcu (Eleonora); T. Rafnar (Thorunn); J.P. Rice (John); S.M. Ring (Susan); F. Rivadeneira Ramirez (Fernando); I. Rudan (Igor); C. Sala (Cinzia); V. Salomaa (Veikko); S. Sanna (Serena); D. Schlessinger; N.J. Schork (Nicholas); A. Scuteri (Angelo); A.V. Segrè (Ayellet); A.R. Shuldiner (Alan); N. Soranzo (Nicole); U. Sovio (Ulla); S.R. Srinivasan (Sathanur); D.P. Strachan (David); M.L. Tammesoo; E. Tikkanen (Emmi); D. Toniolo (Daniela); K. Tsui (Kim); L. Tryggvadottir (Laufey); J.P. Tyrer (Jonathan); M. Uda (Manuela); R.M. van Dam (Rob); J.B.J. van Meurs (Joyce); P. Vollenweider (Peter); G. Waeber (Gérard); N.J. Wareham (Nick); D. Waterworth (Dawn); H.E. Wichmann (Heinz Erich); G.A.H.M. Willemsen (Gonneke); J.F. Wilson (James); A.F. Wright (Alan); L. Young (Lauren); G. Zhai (Guangju); W.V. Zhuang; L.J. Bierut (Laura); D.I. Boomsma (Dorret); H.A. Boyd (Heather); L. Crisponi (Laura); E.W. Demerath (Ellen); P. Tikka-Kleemola (Päivi); M.J. Econs (Michael); T.B. Harris (Tamara); D. Hunter (David); R.J.F. Loos (Ruth); A. Metspalu (Andres); G.W. Montgomery (Grant); P.M. Ridker (Paul); T.D. Spector (Tim); E.A. Streeten (Elizabeth); K. Stefansson (Kari); U. Thorsteinsdottir (Unnur); A.G. Uitterlinden (André); E. Widen (Elisabeth); J. Murabito (Joanne); K. Ong (Ken); M.N. Weedon (Michael)

    2010-01-01

    textabstractTo identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30

  4. Association of vitamin D receptor BsmI gene polymorphism with risk of tuberculosis: a meta-analysis of 15 studies.

    Directory of Open Access Journals (Sweden)

    Yu-Jiao Wu

    Full Text Available BACKGROUND: Genetic variations in vitamin D receptor (VDR may contribute to tuberculosis (TB risk. Many studies have investigated the association between VDR BsmI gene polymorphism and TB risk, but yielded inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a comprehensive meta-analysis of 15 publications with a total of 2309 cases and 3568 controls. We assessed the strength of the association between VDR BsmI gene polymorphism and TB risk and performed sub-group analyses by ethnicity, sample size and Hardy-Weinberg equilibrium (HWE. We found a statistically significant correlation between VDR BsmI gene polymorphism and decreased TB risk in four comparison models: allele model (b vs. B: OR = 0.78, 95% CI = 0.67, 0.89; Pheterogeneity = 0.004, homozygote model (bb vs. BB: OR = 0.61, 95% CI = 0.43, 0.87; Pheterogeneity = 0.001, recessive model (bb vs. Bb+BB: OR = 0.70, 95% CI = 0.56, 0.88; Pheterogeneity = 0.005 and dominant model (bb+Bb vs. BB: OR = 0.77, 95% CI = 0.61, 0.97; Pheterogeneity = 0.010, especially in studies based on Asian population. Sub-group analyses also revealed that there was a statistically decreased TB risk in "small" studies (0.5. Meta-regression and stratification analysis both showed that the ethnicity and sample size contributed to heterogeneity. CONCLUSIONS: This meta-analysis suggests that VDR BsmI gene polymorphism is associated with a significant decreased TB risk, especially in Asian population.

  5. A functional U-statistic method for association analysis of sequencing data.

    Science.gov (United States)

    Jadhav, Sneha; Tong, Xiaoran; Lu, Qing

    2017-11-01

    Although sequencing studies hold great promise for uncovering novel variants predisposing to human diseases, the high dimensionality of the sequencing data brings tremendous challenges to data analysis. Moreover, for many complex diseases (e.g., psychiatric disorders) multiple related phenotypes are collected. These phenotypes can be different measurements of an underlying disease, or measurements characterizing multiple related diseases for studying common genetic mechanism. Although jointly analyzing these phenotypes could potentially increase the power of identifying disease-associated genes, the different types of phenotypes pose challenges for association analysis. To address these challenges, we propose a nonparametric method, functional U-statistic method (FU), for multivariate analysis of sequencing data. It first constructs smooth functions from individuals' sequencing data, and then tests the association of these functions with multiple phenotypes by using a U-statistic. The method provides a general framework for analyzing various types of phenotypes (e.g., binary and continuous phenotypes) with unknown distributions. Fitting the genetic variants within a gene using a smoothing function also allows us to capture complexities of gene structure (e.g., linkage disequilibrium, LD), which could potentially increase the power of association analysis. Through simulations, we compared our method to the multivariate outcome score test (MOST), and found that our test attained better performance than MOST. In a real data application, we apply our method to the sequencing data from Minnesota Twin Study (MTS) and found potential associations of several nicotine receptor subunit (CHRN) genes, including CHRNB3, associated with nicotine dependence and/or alcohol dependence. © 2017 WILEY PERIODICALS, INC.

  6. Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder.

    Science.gov (United States)

    Chen, D T; Jiang, X; Akula, N; Shugart, Y Y; Wendland, J R; Steele, C J M; Kassem, L; Park, J-H; Chatterjee, N; Jamain, S; Cheng, A; Leboyer, M; Muglia, P; Schulze, T G; Cichon, S; Nöthen, M M; Rietschel, M; McMahon, F J; Farmer, A; McGuffin, P; Craig, I; Lewis, C; Hosang, G; Cohen-Woods, S; Vincent, J B; Kennedy, J L; Strauss, J

    2013-02-01

    Meta-analyses of bipolar disorder (BD) genome-wide association studies (GWAS) have identified several genome-wide significant signals in European-ancestry samples, but so far account for little of the inherited risk. We performed a meta-analysis of ∼750,000 high-quality genetic markers on a combined sample of ∼14,000 subjects of European and Asian-ancestry (phase I). The most significant findings were further tested in an extended sample of ∼17,700 cases and controls (phase II). The results suggest novel association findings near the genes TRANK1 (LBA1), LMAN2L and PTGFR. In phase I, the most significant single nucleotide polymorphism (SNP), rs9834970 near TRANK1, was significant at the P=2.4 × 10(-11) level, with no heterogeneity. Supportive evidence for prior association findings near ANK3 and a locus on chromosome 3p21.1 was also observed. The phase II results were similar, although the heterogeneity test became significant for several SNPs. On the basis of these results and other established risk loci, we used the method developed by Park et al. to estimate the number, and the effect size distribution, of BD risk loci that could still be found by GWAS methods. We estimate that >63,000 case-control samples would be needed to identify the ∼105 BD risk loci discoverable by GWAS, and that these will together explain <6% of the inherited risk. These results support previous GWAS findings and identify three new candidate genes for BD. Further studies are needed to replicate these findings and may potentially lead to identification of functional variants. Sample size will remain a limiting factor in the discovery of common alleles associated with BD.

  7. Association between polymorphism within interleukin related genes and Graves' disease: a meta-analysis of 22 case-control studies

    Science.gov (United States)

    Zeng, Tianshu; Cai, Xiong; Kong, Wen

    2017-01-01

    Graves’ disease (GD) is a common autoimmune disorder with a genetic predisposition. There is strong evidence to suggest that both Th1 and Th2 circulating cytokines are involved in the development of GD. In this study, we conducted a meta-analysis to assess the impact of seven variations of five IL-related genes on the susceptibility to GD. A total of 22 case-control studies involving 5338 GD patients and 6446 healthy controls were included. The results showed that only one SNP rs1800795 in IL-6 was significantly associated with GD in homozygous model (CC vs. GG: OR = 2.714, 95% CI = 1.047–7.039, p = 0.04), heterozygous model (CG vs. GG: OR = 1.295, 95% CI = 1.013–1.655, p = 0.039), dominant model (CC+CG vs. GG: OR = 1.418, 95% CI = 1.122–1.793, p = 0.003) and additive model (C vs. G: OR = 1.432, 95% CI = 1.087–1.886, p = 0.011).To explain the heterogeneity, we performed the subgroup analysis by ethnicity. The ethnicity stratification revealed that the association between rs1800795 and GD tended to be much stronger for Asian than European population in homozygous, dominant, recessive, and additive models. The remaining 6 SNPs in 4 genes did not show any significant association with GD in any genetic models. Together, our data support that rs1800795 within the IL-6 gene confers genetic susceptibility for GD. Future large-scale studies are required to validate the associations between IL-6 and others IL-related genes and GD. PMID:29228744

  8. Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative.

    Science.gov (United States)

    Wang, Jun; Kurilshikov, Alexander; Radjabzadeh, Djawad; Turpin, Williams; Croitoru, Kenneth; Bonder, Marc Jan; Jackson, Matthew A; Medina-Gomez, Carolina; Frost, Fabian; Homuth, Georg; Rühlemann, Malte; Hughes, David; Kim, Han-Na; Spector, Tim D; Bell, Jordana T; Steves, Claire J; Timpson, Nicolas; Franke, Andre; Wijmenga, Cisca; Meyer, Katie; Kacprowski, Tim; Franke, Lude; Paterson, Andrew D; Raes, Jeroen; Kraaij, Robert; Zhernakova, Alexandra

    2018-06-08

    In recent years, human microbiota, especially gut microbiota, have emerged as an important yet complex trait influencing human metabolism, immunology, and diseases. Many studies are investigating the forces underlying the observed variation, including the human genetic variants that shape human microbiota. Several preliminary genome-wide association studies (GWAS) have been completed, but more are necessary to achieve a fuller picture. Here, we announce the MiBioGen consortium initiative, which has assembled 18 population-level cohorts and some 19,000 participants. Its aim is to generate new knowledge for the rapidly developing field of microbiota research. Each cohort has surveyed the gut microbiome via 16S rRNA sequencing and genotyped their participants with full-genome SNP arrays. We have standardized the analytical pipelines for both the microbiota phenotypes and genotypes, and all the data have been processed using identical approaches. Our analysis of microbiome composition shows that we can reduce the potential artifacts introduced by technical differences in generating microbiota data. We are now in the process of benchmarking the association tests and performing meta-analyses of genome-wide associations. All pipeline and summary statistics results will be shared using public data repositories. We present the largest consortium to date devoted to microbiota-GWAS. We have adapted our analytical pipelines to suit multi-cohort analyses and expect to gain insight into host-microbiota cross-talk at the genome-wide level. And, as an open consortium, we invite more cohorts to join us (by contacting one of the corresponding authors) and to follow the analytical pipeline we have developed.

  9. Identification of novel risk genes associated with type 1 diabetes mellitus using a genome-wide gene-based association analysis.

    Science.gov (United States)

    Qiu, Ying-Hua; Deng, Fei-Yan; Li, Min-Jing; Lei, Shu-Feng

    2014-11-01

    Type 1 diabetes mellitus is a serious disorder characterized by destruction of pancreatic β-cells, culminating in absolute insulin deficiency. Genetic factors contribute to the susceptibility of type 1 diabetes mellitus. The aim of the present study was to identify more susceptibility genes of type 1 diabetes mellitus. We carried out an initial gene-based genome-wide association study in a total of 4,075 type 1 diabetes mellitus cases and 2,604 controls by using the Gene-based Association Test using Extended Simes procedure. Furthermore, we carried out replication studies, differential expression analysis and functional annotation clustering analysis to support the significance of the identified susceptibility genes. We identified 452 genes associated with type 1 diabetes mellitus, even after adapting the genome-wide threshold for significance (P diabetes mellitus, which were ignored in single-nucleotide polymorphism-based association analysis and were not previously reported. We found that 53 genes have supportive evidence from replication studies and/or differential expression studies. In particular, seven genes including four non-human leukocyte antigen (HLA) genes (RASIP1, STRN4, BCAR1 and MYL2) are replicated in at least one independent population and also differentially expressed in peripheral blood mononuclear cells or monocytes. Furthermore, the associated genes tend to enrich in immune-related pathways or Gene Ontology project terms. The present results suggest the high power of gene-based association analysis in detecting disease-susceptibility genes. Our findings provide more insights into the genetic basis of type 1 diabetes mellitus.

  10. SNPassoc: an R package to perform whole genome association studies.

    Science.gov (United States)

    González, Juan R; Armengol, Lluís; Solé, Xavier; Guinó, Elisabet; Mercader, Josep M; Estivill, Xavier; Moreno, Víctor

    2007-03-01

    The popularization of large-scale genotyping projects has led to the widespread adoption of genetic association studies as the tool of choice in the search for single nucleotide polymorphisms (SNPs) underlying susceptibility to complex diseases. Although the analysis of individual SNPs is a relatively trivial task, when the number is large and multiple genetic models need to be explored it becomes necessary a tool to automate the analyses. In order to address this issue, we developed SNPassoc, an R package to carry out most common analyses in whole genome association studies. These analyses include descriptive statistics and exploratory analysis of missing values, calculation of Hardy-Weinberg equilibrium, analysis of association based on generalized linear models (either for quantitative or binary traits), and analysis of multiple SNPs (haplotype and epistasis analysis). Package SNPassoc is available at CRAN from http://cran.r-project.org. A tutorial is available on Bioinformatics online and in http://davinci.crg.es/estivill_lab/snpassoc.

  11. Association between omega-3 fatty acids consumption and the risk of type 2 diabetes: A meta-analysis of cohort studies.

    Science.gov (United States)

    Chen, Cai; Yang, Yan; Yu, Xuefeng; Hu, Shuhong; Shao, Shiying

    2017-07-01

    Epidemiological evidence for the effect of omega-3 fatty acids on the risk of type 2 diabetes is controversial. A meta-analysis based on prospective cohorts was carried out to evaluate this issue. Pooled diabetic risk was calculated using a fixed or random effects model. The dose-response relationship was assessed by meta-regression analysis. The study showed that consumption of single omega-3 was associated with an increased risk of type 2 diabetes (relative risk [RR] = 1.45, P omega-3 was statistically insignificant. The dose-response curve presented an inverted U-shape of diabetes risk corresponding to the dose of omega-3 consumption. Subanalysis showed that omega-3 was inversely associated with type 2 diabetes risk in Asians (RR = 0.82, P omega-3 intake. The present findings suggest that dosage and composition of omega-3, ethnicity, trial duration, and age could influence the effect of omega-3 on type 2 diabetes progression. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  12. Dynamic association rules for gene expression data analysis.

    Science.gov (United States)

    Chen, Shu-Chuan; Tsai, Tsung-Hsien; Chung, Cheng-Han; Li, Wen-Hsiung

    2015-10-14

    The purpose of gene expression analysis is to look for the association between regulation of gene expression levels and phenotypic variations. This association based on gene expression profile has been used to determine whether the induction/repression of genes correspond to phenotypic variations including cell regulations, clinical diagnoses and drug development. Statistical analyses on microarray data have been developed to resolve gene selection issue. However, these methods do not inform us of causality between genes and phenotypes. In this paper, we propose the dynamic association rule algorithm (DAR algorithm) which helps ones to efficiently select a subset of significant genes for subsequent analysis. The DAR algorithm is based on association rules from market basket analysis in marketing. We first propose a statistical way, based on constructing a one-sided confidence interval and hypothesis testing, to determine if an association rule is meaningful. Based on the proposed statistical method, we then developed the DAR algorithm for gene expression data analysis. The method was applied to analyze four microarray datasets and one Next Generation Sequencing (NGS) dataset: the Mice Apo A1 dataset, the whole genome expression dataset of mouse embryonic stem cells, expression profiling of the bone marrow of Leukemia patients, Microarray Quality Control (MAQC) data set and the RNA-seq dataset of a mouse genomic imprinting study. A comparison of the proposed method with the t-test on the expression profiling of the bone marrow of Leukemia patients was conducted. We developed a statistical way, based on the concept of confidence interval, to determine the minimum support and minimum confidence for mining association relationships among items. With the minimum support and minimum confidence, one can find significant rules in one single step. The DAR algorithm was then developed for gene expression data analysis. Four gene expression datasets showed that the proposed

  13. Lack of association between NADPH quinone oxidoreductase 1 (NQO1 gene C609T polymorphism and lung cancer: a case-control study and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Shujie Guo

    Full Text Available BACKGROUND: The association between NAD(PH:quinone oxidoreductase 1 (NQO1 gene C609T polymorphism (rs1800566 and lung cancer has been widely evaluated, and a definitive answer so far is lacking. We first conducted a case-control study to assess this association in northeastern Han Chinese, and then performed a meta-analysis to further address this issue. METHODOLOGY/PRINCIPAL FINDINGS: This case-control study involved 684 patients clinically diagnosed as lung cancer and 602 age-matched cancer-free controls from Harbin city, Heilongjiang province, China. Genotyping was conducted using the PCR-LDR (ligase detection reactions method. Meta-analysis was managed by STATA software. Data and study quality were assessed in duplicate. Our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between lung cancer patients and controls, consistent with the results of the further meta-analysis involving 7286 patients and 9167 controls under both allelic (odds ratio (OR = 0.99; 95% confidence interval (CI: 0.92-1.06; P = 0.692 and dominant (OR = 0.98; 95% CI: 0.89-1.08; P = 0.637 models. However, there was moderate evidence of between-study heterogeneity and low probability of publication bias. Further subgroup analyses by ethnicity, source of controls and sample size detected no positive associations in this meta-analysis. CONCLUSIONS: Our study in northeastern Han Chinese, along with the meta-analysis, failed to confirm the association of NQO1 gene C609T polymorphism with lung cancer risk, even across different ethnic populations.

  14. The SLC4A7 variant rs4973768 is associated with breast cancer risk: evidence from a case-control study and a meta-analysis.

    Science.gov (United States)

    Chen, Wei; Zhong, Rong; Ming, Jie; Zou, Li; Zhu, Beibei; Lu, Xuzai; Ke, Juntao; Zhang, Yu; Liu, Li; Miao, Xiaoping; Huang, Tao

    2012-12-01

    Recent genome-wide association study has identified a genetic variant rs4973768, located in 3'-UTR of solute carrier family 4, sodium bicarbonate cotransporter, member 7 (SLC4A7), was associated with increased risk of breast cancer (BC). However, several following replication studies cannot yield consistent results. We thus conducted a hospital-based case-control study including 485 patients and 514 controls, combined a meta-analysis including 108,632 cases and 135,818 controls to explore the relationship between this variant and BC risk. Our case-control study showed that rs4973768 was significantly associated with increased BC risk with the odds ratio (OR) of 1.29 (95 % confidence interval [CI]: 1.04-1.60) under the allelic model. In addition, the meta-analysis also indicated that the variant slightly increased the risk of BC with the pooled OR of the per-allele effect being 1.08 (95 % CI: 1.04-1.11) although with significant heterogeneity between studies. Stratified analyses showed that ethnicity, sample size, and study design may explain part of the heterogeneity. Moreover, the bioinformatics analysis suggested that this variant may influence the transcriptional capacity of SLC4A7. In summary, our results showed that the SLC4A7 variant, rs4973768, is associated with risk of BC although the underlying biologic mechanism warrants further studies.

  15. Association between XPF polymorphisms and cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Ting-Yan Shi

    Full Text Available BACKGROUND: Xeroderma pigmentosum complementation group F (XPF or ERCC4 plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: In this meta-analysis of 47,639 cancer cases and 51,915 controls, by searching three electronic databases (i.e., MEDLINE, EMBASE and CNKI, we summarized 43 case-control studies from 29 publications on four commonly studied polymorphisms of XPF (i.e., rs1800067, rs1799801, rs2020955 and rs744154, and we did not find statistical evidence of any significant association with overall cancer risk. However, in stratification analyses, we found a significant association of XPF-rs1799801 with a reduced cancer risk in Caucasian populations (4,845 cases and 5,556 controls; recessive model: OR=0.87, 95% CI=0.76-1.00, P=0.049, P=0.723 for heterogeneity test, I(2 =0. Further genotype-phenotype correlation analysis showed that the homozygous variant CC genotype carriers had higher XPF expression levels than that of the TT genotype carriers (Student's t test for a recessive model: P=0.046. No publication bias was found by using the funnel plot and Egger's test. CONCLUSION: This meta-analysis suggests a lack of statistical evidence for the association between the four XPF SNPs and overall risk of cancers. However, XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies.

  16. Associations between interleukin-1 polymorphisms and susceptibility to vasculitis: a meta-analysis.

    Science.gov (United States)

    Song, G G; Kim, J-H; Lee, Y H

    2016-05-01

    The objective of this study was to determine whether interleukin-1 (IL-1) polymorphisms are associated with susceptibility to vasculitis. A meta-analysis was conducted to investigate possible associations between IL-1A, IL-1B, and IL-1 receptor antagonist (IL1RN) polymorphisms and vasculitis. A total of 17 studies involving 1384 vasculitis cases [Behçet's disease (BD), IgA vasculitis, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), Kawasaki disease (KD), giant cell arteritis, and Takayasu's arteritis] and 2710 controls were included in the meta-analysis. This analysis showed an association between BD and the TT + TC genotypes of the IL-1A-889 C/T polymorphism in the entire study population [odds ratio (OR) = 0.623, 95 % CI = 0.395-0.981, p = 0.045), and a trend toward an association in a Turkish population (OR = 0.578, 95 % CI = 0.331-1.010, p = 0.054). A meta-analysis of the IL1RN polymorphism revealed no association with vasculitis in all study subjects (OR for IL1RN*2 = 0.904, 95 % CI = 0.626-1.304, p = 0.588). However, stratification by ethnicity revealed a significant association between the IL1RN*2 allele and vasculitis including AAV, BD, KD in Asians (OR = 2.393, 95 % CI = 1.429-4.006, p = 0.001), but not in Caucasian and Turkish populations (OR = 0.776, 95 % CI = 0.487-1.238, p = 0.288; OR = 0.914, 95 % CI = 0.667-1.252, p = 0.576, respectively). No association was found between vasculitis and the IL-1B-511 C/T polymorphism, or the IL-1B+3953 C/T polymorphism. This meta-analysis suggests that the IL-1A-889 C/T polymorphism is associated with susceptibility to BD, and that the IL1RN*2 allele is associated with susceptibility to vasculitis including AAV, BD, and KD in Asians.

  17. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

    Science.gov (United States)

    Davies, G; Armstrong, N; Bis, J C; Bressler, J; Chouraki, V; Giddaluru, S; Hofer, E; Ibrahim-Verbaas, C A; Kirin, M; Lahti, J; van der Lee, S J; Le Hellard, S; Liu, T; Marioni, R E; Oldmeadow, C; Postmus, I; Smith, A V; Smith, J A; Thalamuthu, A; Thomson, R; Vitart, V; Wang, J; Yu, L; Zgaga, L; Zhao, W; Boxall, R; Harris, S E; Hill, W D; Liewald, D C; Luciano, M; Adams, H; Ames, D; Amin, N; Amouyel, P; Assareh, A A; Au, R; Becker, J T; Beiser, A; Berr, C; Bertram, L; Boerwinkle, E; Buckley, B M; Campbell, H; Corley, J; De Jager, P L; Dufouil, C; Eriksson, J G; Espeseth, T; Faul, J D; Ford, I; Scotland, Generation; Gottesman, R F; Griswold, M E; Gudnason, V; Harris, T B; Heiss, G; Hofman, A; Holliday, E G; Huffman, J; Kardia, S L R; Kochan, N; Knopman, D S; Kwok, J B; Lambert, J-C; Lee, T; Li, G; Li, S-C; Loitfelder, M; Lopez, O L; Lundervold, A J; Lundqvist, A; Mather, K A; Mirza, S S; Nyberg, L; Oostra, B A; Palotie, A; Papenberg, G; Pattie, A; Petrovic, K; Polasek, O; Psaty, B M; Redmond, P; Reppermund, S; Rotter, J I; Schmidt, H; Schuur, M; Schofield, P W; Scott, R J; Steen, V M; Stott, D J; van Swieten, J C; Taylor, K D; Trollor, J; Trompet, S; Uitterlinden, A G; Weinstein, G; Widen, E; Windham, B G; Jukema, J W; Wright, A F; Wright, M J; Yang, Q; Amieva, H; Attia, J R; Bennett, D A; Brodaty, H; de Craen, A J M; Hayward, C; Ikram, M A; Lindenberger, U; Nilsson, L-G; Porteous, D J; Räikkönen, K; Reinvang, I; Rudan, I; Sachdev, P S; Schmidt, R; Schofield, P R; Srikanth, V; Starr, J M; Turner, S T; Weir, D R; Wilson, J F; van Duijn, C; Launer, L; Fitzpatrick, A L; Seshadri, S; Mosley, T H; Deary, I J

    2015-01-01

    General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C. PMID:25644384

  18. Synthetic analysis of associations between IL-10 polymorphisms and skin cancer risk.

    Science.gov (United States)

    Zhao, Hongbo; Yang, Jiaoli; Yu, Zhenzhen; Shen, Hui; Huang, Xinlin; Zhang, Mi; Long, Teng; Cailing, A; Wang, Wenhui

    2018-01-23

    The current study was designed to quantitatively summarize the evidence for the strength of the associations between common IL-10 functional polymorphisms and skin cancer risk. Relevant publications concerning the associations between common IL-10 functional polymorphisms(-1082G>A, -819C>T and -592C>A) and skin cancer were retrieved by a comprehensive electronic literature search in PubMed, Web of Science, EBSCO, Embase, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database (CBM). The odds ratio (OR) and 95% confidence interval (CI) were utilized to assess the strength of the relationship. A total of 26 studies including 4090 cases and 4133 controls (-1082G>A, 10 studies with 1809 cases and 1830 controls; -819C>T, 7 studies with 862 cases and 957 controls; -592C>A, 9 studies with 1419 cases and 1346 controls) were enrolled in the meta-analysis. Overall, the results revealed a borderline decreased risk of skin cancer in heterozygote model (OR = 0.82, 95CI = 0.67-1.00, p = 0.05). The subgroup analysis also presented similar association for non-melanoma skin cancer in heterozygote model (OR = 0.67, 95CI = 0.50-0.91, p = 0.01). Moreover, the further analysis based on the histological type of non-melanoma skin cancer indicated a significantly decreased risk of BCC in allele model (OR = 0.67, 95% CI = 0.50-0.91, p = 0.02) and dominant model (OR = 0.68, 95% CI = 0.48-0.98, p = 0.04). However, neither overall analysis nor subgroup analysis based on cancer subtype revealed a significant association of -1082G>A or -592C>A polymorphisms with skin cancer. The present study suggested a potential association between IL-10 -819C>T polymorphism and decreased risk of skin cancer, but a lack of association for -1082G>A and -592C>A polymorphisms. Further invalidation is urgently needed.

  19. Lack of association of poultry and eggs intake with risk of non-Hodgkin lymphoma: a meta-analysis of observational studies.

    Science.gov (United States)

    Dong, Y; Wu, G

    2017-09-01

    We carried out a meta-analysis to explore the association between poultry and eggs consumption and non-Hodgkin lymphoma (NHL) risk according to the published observational studies. A search of databases was performed in MEDLINE and EMBASE from their inception to March 2015. We derived meta-analytic estimates using random-effects models, and assessed between-study heterogeneity using the Cochran's Q and I 2 statistics. We identified a total of nine case-control and three prospective cohort studies, including 11,271 subjects with NHL. The summary relative risks for high vs. low analyses were 1.04 (95% confidence intervals [CIs]: 0.86-1.27; p heterogeneity poultry consumption and 1.15 (95% CIs: 0.87-1.51; p heterogeneity poultry consumption, whereas no significant factors were responsible for the high heterogeneity among the studies on eggs consumption. Limited data suggested a null association between consumption of poultry and eggs and NHL subtypes. Findings from our meta-analysis indicate that consumption of poultry and eggs may be not related to NHL risk. © 2016 John Wiley & Sons Ltd.

  20. A Study of the Factors Associated with Risk for Development of Pressure Ulcers: A Longitudinal Analysis.

    Science.gov (United States)

    Thomas, Elizebeth; Vinodkumar, Sudhaya; Mathew, Silvia; Setia, Maninder Singh

    2015-01-01

    Pressure ulcers (PUs) are prevalent in hospitalized patients; they may cause clinical, psychological, and economic problems in these patients. Previous studies are cross-sectional, have used pooled data, or cox-regression models to assess the risk for developing PU. However, PU risk scores change over time and models that account for time varying variables are useful for cohort analysis of data. The present longitudinal study was conducted to compare the risk of PU between surgical and nonsurgical patients, and to evaluate the factors associated with the development of these ulcers over a period of time. We evaluated 290 hospitalized patients over a 4 months period. The main outcomes for our analysis were: (1) Score on the pressure risk assessment scale; and (2) the proportion of individuals who were at severe risk for developing PUs. We used random effects models for longitudinal analysis of the data. The mean PU score was significantly higher in the nonsurgical patients compared with surgical patients at baseline (15.23 [3.86] vs. 9.33 [4.57]; P 20 at baseline and were considered as being at high-risk for PU; the proportion was significantly higher among the nonsurgical patients compared with the surgical patients (14% vs. 4%, P = 0.003). In the adjusted models, there was no difference for severe risk for PU between surgical and nonsurgical patients (odds ratios [ORs]: 0.37, 95% confidence interval [CI]: 0.01-12.80). An additional day in the ward was associated with a significantly higher likelihood of being at high-risk for PU (OR: 1.47, 95% CI: 1.16-1.86). There were no significant differences between patients who were admitted for surgery compared with those who were not. An additional day in the ward, however, is important for developing a high-risk score for PU on the monitoring scale, and these patients require active interventions.

  1. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

    Directory of Open Access Journals (Sweden)

    Alexandra Zhernakova

    2011-02-01

    Full Text Available Epidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD and rheumatoid arthritis (RA, but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls and RA (5,539 cases and 17,231 controls. After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P<5 × 10(-8 in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (P(combined =  1.2 × 10(-12, rs864537 near CD247 (P(combined =  2.2 × 10(-11, rs2298428 near UBE2L3 (P(combined =  2.5 × 10(-10, and rs11203203 near UBASH3A (P(combined =  1.1 × 10(-8. We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5 × 10(-8 (SH2B3, 8q24, STAT4, and TRAF1-C5. From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases.

  2. Association of OPN rs11730582 polymorphism with cancer risk: a meta-analysis

    Directory of Open Access Journals (Sweden)

    He LL

    2016-03-01

    Full Text Available Lanlan He,1,* Yong Wang2,* 1Emergency Department, Zhenjiang First People’s Hospital, Zhenjiang, People’s Republic of China; 2Department of Interventional Radiology and Vascular Surgery, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of China *Both authors contributed equally to this work Purpose: Several molecular epidemiological studies have investigated the association between OPN rs11730582 C>T polymorphism and cancer risk, but the results are inconsistent. Hence, a meta-analysis was conducted to determine the association of this polymorphism with cancer risk. Materials and methods: The related articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases. Pooled odds ratios and 95% confidence intervals were calculated to evaluate the strength of the associations. A random-effects model or fixed-effects model was employed depending on the heterogeneity. Results: A total of ten case-control studies involving 2,749 cancer cases and 3,398 controls were included in the meta-analysis. In overall analysis, OPN rs11730582 C>T polymorphism was not associated with cancer risk. In a stratified analysis by cancer type, no significant association was found between OPN rs11730582 C>T polymorphism and the risk of glioma, gastric cancer, and other cancers. Conclusion: This meta-analysis suggests that OPN rs11730582 C>T polymorphism is not associated with cancer susceptibility. Keywords: osteopontin, polymorphism, cancer, risk 

  3. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

    NARCIS (Netherlands)

    H. Schunkert (Heribert); I.R. König (Inke); S. Kathiresan (Sekar); M.P. Reilly (Muredach); T.L. Assimes (Themistocles); H. Holm (Hilma); M. Preuss (Michael); A.F.R. Stewart (Alexandre); M. Barbalic (maja); C. Gieger (Christian); D. Absher (Devin); Z. Aherrahrou (Zouhair); H. Allayee (Hooman); D. Altshuler (David); S.S. Anand (Sonia); K.K. Andersen (Karl); J.L. Anderson (Jeffrey); D. Ardissino (Diego); S.G. Ball (Stephen); A.J. Balmforth (Anthony); T.A. Barnes (Timothy); D.M. Becker (Diane); K. Berger (Klaus); J.C. Bis (Joshua); S.M. Boekholdt (Matthijs); E.A. Boerwinkle (Eric); P.S. Braund (Peter); M.J. Brown (Morris); M.S. Burnett; I. Buysschaert (Ian); J.F. Carlquist (John); L. Chen (Li); S. Cichon (Sven); V. Codd (Veryan); R.W. Davies (Robert); G.V. Dedoussis (George); A. Dehghan (Abbas); S. Demissie (Serkalem); J. Devaney (Joseph); P. Diemert (Patrick); R. Do (Ron); A. Doering (Angela); S. Eifert (Sandra); N.E.E. Mokhtari; S.G. Ellis (Stephen); R. Elosua (Roberto); J.C. Engert (James); S.E. Epstein (Stephen); U. de Faire (Ulf); M. Fischer (Marcus); A.R. Folsom (Aaron); J. Freyer (Jennifer); B. Gigante (Bruna); D. Girelli (Domenico); S. Gretarsdottir (Solveig); V. Gudnason (Vilmundur); J.R. Gulcher (Jeffrey); E. Halperin (Eran); N. Hammond (Naomi); S.L. Hazen (Stanley); A. Hofman (Albert); B.D. Horne (Benjamin); T. Illig (Thomas); C. Iribarren (Carlos); G.T. Jones (Gregory); J.W. Jukema (Jan Wouter); M.A. Kaiser (Michael); R.C. Kaplan (Robert); K-T. Khaw (Kay-Tee); J.W. Knowles (Joshua); G. Kolovou (Genovefa); A. Kong (Augustine); R. Laaksonen (Reijo); D. Lambrechts (Diether); K. Leander (Karin); G. Lettre (Guillaume); X. Li (Xiaohui); W. Lieb (Wolfgang); C. Loley (Christina); A.J. Lotery (Andrew); P.M. Mannucci (Pier); S. Maouche (Seraya); N. Martinelli (Nicola); P.P. McKeown (Pascal); C. Meisinger (Christa); T. Meitinger (Thomas); O. Melander (Olle); P.A. Merlini; V. Mooser (Vincent); T. Morgan (Thomas); T.W. Mühleisen (Thomas); J.B. Muhlestein (Joseph); T. Münzel (Thomas); K. Musunuru (Kiran); J. Nahrstaedt (Janja); C.P. Nelson (Christopher P.); M.M. Nöthen (Markus); O. Olivieri (Oliviero); R.S. Patel (Riyaz); C.C. Patterson (Chris); A. Peters (Annette); F. Peyvandi (Flora); L. Qu (Liming); A.A. Quyyumi (Arshed); D.J. Rader (Daniel); L.S. Rallidis (Loukianos); C. Rice (Catherine); F.R. Rosendaal (Frits); D. Rubin (Diana); V. Salomaa (Veikko); M.L. Sampietro (Maria Lourdes); M.S. Sandhu (Manj); E.E. Schadt (Eric); A. Scḧsignfer (Arne); A. Schillert (Arne); S. Schreiber (Stefan); J. Schrezenmeir (Jürgen); S.M. Schwartz (Stephen); D.S. Siscovick (David); M. Sivananthan (Mohan); S. Sivapalaratnam (Suthesh); A.V. Smith (Albert Vernon); J.D. Snoep (Jaapjan); N. Soranzo (Nicole); J.A. Spertus (John); K. Stark (Klaus); K. Stirrups (Kathy); M. Stoll (Monika); W.H.W. Tang (Wilson); S. Tennstedt (Stephanie); G. Thorgeirsson (Gudmundur); G. Thorleifsson (Gudmar); M. Tomaszewski (Maciej); A.G. Uitterlinden (André); A.M. van Rij (Andre); B.F. Voight (Benjamin); N.J. Wareham (Nick); G.A. Wells (George); H.E. Wichmann (Heinz Erich); P.S. Wild (Philipp); C. Willenborg (Christina); J.C.M. Witteman (Jacqueline); B.J. Wright (Benjamin); S. Ye (Shu); T. Zeller (Tanja); A. Ziegler (Andreas); F. Cambien (François); A.H. Goodall (Alison); L.A. Cupples (Adrienne); T. Quertermous (Thomas); W. Mäsignrz (Winfried); C. Hengstenberg (Christian); S. Blankenberg (Stefan); W.H. Ouwehand (Willem); A.S. Hall (Alistair); J.J.P. Kastelein (John); P. Deloukas (Panagiotis); J.R. Thompson (John); K. Stefansson (Kari); R. Roberts (Robert); U. Thorsteinsdottir (Unnur); C.J. O'Donnell (Christopher); R. McPherson (Ruth); J. Erdmann (Jeanette); N.J. Samani (Nilesh)

    2011-01-01

    textabstractWe performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis

  4. Bayesian Graphical Models for Genomewide Association Studies

    OpenAIRE

    Verzilli, Claudio J.; Stallard, Nigel; Whittaker, John C.

    2006-01-01

    As the extent of human genetic variation becomes more fully characterized, the research community is faced with the challenging task of using this information to dissect the heritable components of complex traits. Genomewide association studies offer great promise in this respect, but their analysis poses formidable difficulties. In this article, we describe a computationally efficient approach to mining genotype-phenotype associations that scales to the size of the data sets currently being ...

  5. Capturing the spectrum of interaction effects in genetic association studies by simulated evaporative cooling network analysis.

    Directory of Open Access Journals (Sweden)

    Brett A McKinney

    2009-03-01

    Full Text Available Evidence from human genetic studies of several disorders suggests that interactions between alleles at multiple genes play an important role in influencing phenotypic expression. Analytical methods for identifying Mendelian disease genes are not appropriate when applied to common multigenic diseases, because such methods investigate association with the phenotype only one genetic locus at a time. New strategies are needed that can capture the spectrum of genetic effects, from Mendelian to multifactorial epistasis. Random Forests (RF and Relief-F are two powerful machine-learning methods that have been studied as filters for genetic case-control data due to their ability to account for the context of alleles at multiple genes when scoring the relevance of individual genetic variants to the phenotype. However, when variants interact strongly, the independence assumption of RF in the tree node-splitting criterion leads to diminished importance scores for relevant variants. Relief-F, on the other hand, was designed to detect strong interactions but is sensitive to large backgrounds of variants that are irrelevant to classification of the phenotype, which is an acute problem in genome-wide association studies. To overcome the weaknesses of these data mining approaches, we develop Evaporative Cooling (EC feature selection, a flexible machine learning method that can integrate multiple importance scores while removing irrelevant genetic variants. To characterize detailed interactions, we construct a genetic-association interaction network (GAIN, whose edges quantify the synergy between variants with respect to the phenotype. We use simulation analysis to show that EC is able to identify a wide range of interaction effects in genetic association data. We apply the EC filter to a smallpox vaccine cohort study of single nucleotide polymorphisms (SNPs and infer a GAIN for a collection of SNPs associated with adverse events. Our results suggest an important

  6. Genome-wide association study identifies genetic loci associated with iron deficiency.

    Directory of Open Access Journals (Sweden)

    Christine E McLaren

    2011-03-01

    Full Text Available The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS was performed using DNA collected from white men aged≥25 y and women≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS Study with serum ferritin (SF≤12 µg/L (cases and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women. Regression analysis was used to examine the association between case-control status (336 cases, 343 controls and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10(-7 for all. An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P=7.0×10(-9, corrected P=0.012 was replicated within the VA samples (observed P=0.012. Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification.

  7. Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    David M. Howard

    2017-08-01

    Full Text Available Background: Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. Methods: In the present analysis, three cohort studies (ntotal = 48,002 were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS, the English Longitudinal Study of Ageing (ELSA, and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. Results: None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P-value overlapped with the D-amino acid oxidase activator (DAOA gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer’s disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10-7, was the butyrylcholinesterase (BCHE gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer’s disease and its role in cognitive ability merits further investigation. Conclusions: Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect.

  8. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

    NARCIS (Netherlands)

    Schunkert, Heribert; König, Inke R.; Kathiresan, Sekar; Reilly, Muredach P.; Assimes, Themistocles L.; Holm, Hilma; Preuss, Michael; Stewart, Alexandre F. R.; Barbalic, Maja; Gieger, Christian; Absher, Devin; Aherrahrou, Zouhair; Allayee, Hooman; Altshuler, David; Anand, Sonia S.; Andersen, Karl; Anderson, Jeffrey L.; Ardissino, Diego; Ball, Stephen G.; Balmforth, Anthony J.; Barnes, Timothy A.; Becker, Diane M.; Becker, Lewis C.; Berger, Klaus; Bis, Joshua C.; Boekholdt, S. Matthijs; Boerwinkle, Eric; Braund, Peter S.; Brown, Morris J.; Burnett, Mary Susan; Buysschaert, Ian; Carlquist, John F.; Chen, Li; Cichon, Sven; Codd, Veryan; Davies, Robert W.; Dedoussis, George; Dehghan, Abbas; Demissie, Serkalem; Devaney, Joseph M.; Diemert, Patrick; Do, Ron; Doering, Angela; Eifert, Sandra; Mokhtari, Nour Eddine El; Ellis, Stephen G.; Elosua, Roberto; Engert, James C.; Epstein, Stephen E.; de Faire, Ulf; Fischer, Marcus; Folsom, Aaron R.; Freyer, Jennifer; Gigante, Bruna; Girelli, Domenico; Gretarsdottir, Solveig; Gudnason, Vilmundur; Gulcher, Jeffrey R.; Halperin, Eran; Hammond, Naomi; Hazen, Stanley L.; Hofman, Albert; Horne, Benjamin D.; Illig, Thomas; Iribarren, Carlos; Jones, Gregory T.; Jukema, J. Wouter; Kaiser, Michael A.; Kaplan, Lee M.; Kastelein, John J. P.; Khaw, Kay-Tee; Knowles, Joshua W.; Kolovou, Genovefa; Kong, Augustine; Laaksonen, Reijo; Lambrechts, Diether; Leander, Karin; Lettre, Guillaume; Li, Mingyao; Lieb, Wolfgang; Loley, Christina; Lotery, Andrew J.; Mannucci, Pier M.; Maouche, Seraya; Martinelli, Nicola; McKeown, Pascal P.; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Merlini, Pier Angelica; Mooser, Vincent; Morgan, Thomas; Mühleisen, Thomas W.; Muhlestein, Joseph B.; Münzel, Thomas; Musunuru, Kiran; Nahrstaedt, Janja; Nelson, Christopher P.; Nöthen, Markus M.; Olivieri, Oliviero; Patel, Riyaz S.; Patterson, Chris C.; Peters, Annette; Peyvandi, Flora; Qu, Liming; Quyyumi, Arshed A.; Rader, Daniel J.; Rallidis, Loukianos S.; Rice, Catherine; Rosendaal, Frits R.; Rubin, Diana; Salomaa, Veikko; Sampietro, M. Lourdes; Sandhu, Manj S.; Schadt, Eric; Schäfer, Arne; Schillert, Arne; Schreiber, Stefan; Schrezenmeir, Jürgen; Schwartz, Stephen M.; Siscovick, David S.; Sivananthan, Mohan; Sivapalaratnam, Suthesh; Smith, Albert; Smith, Tamara B.; Snoep, Jaapjan D.; Soranzo, Nicole; Spertus, John A.; Stark, Klaus; Stirrups, Kathy; Stoll, Monika; Tang, W. H. Wilson; Tennstedt, Stephanie; Thorgeirsson, Gudmundur; Thorleifsson, Gudmar; Tomaszewski, Maciej; Uitterlinden, Andre G.; van Rij, Andre M.; Voight, Benjamin F.; Wareham, Nick J.; Wells, George A.; Wichmann, H.-Erich; Wild, Philipp S.; Willenborg, Christina; Witteman, Jaqueline C. M.; Wright, Benjamin J.; Ye, Shu; Zeller, Tanja; Ziegler, Andreas; Cambien, Francois; Goodall, Alison H.; Cupples, L. Adrienne; Quertermous, Thomas; März, Winfried; Hengstenberg, Christian; Blankenberg, Stefan; Ouwehand, Willem H.; Hall, Alistair S.; Deloukas, Panos; Thompson, John R.; Stefansson, Kari; Roberts, Robert; Thorsteinsdottir, Unnur; O'Donnell, Christopher J.; McPherson, Ruth; Erdmann, Jeanette; Samani, Nilesh J.

    2011-01-01

    We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13

  9. Genome-wide association study of pathological gambling.

    Science.gov (United States)

    Lang, M; Leménager, T; Streit, F; Fauth-Bühler, M; Frank, J; Juraeva, D; Witt, S H; Degenhardt, F; Hofmann, A; Heilmann-Heimbach, S; Kiefer, F; Brors, B; Grabe, H-J; John, U; Bischof, A; Bischof, G; Völker, U; Homuth, G; Beutel, M; Lind, P A; Medland, S E; Slutske, W S; Martin, N G; Völzke, H; Nöthen, M M; Meyer, C; Rumpf, H-J; Wurst, F M; Rietschel, M; Mann, K F

    2016-08-01

    Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence. Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence. No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value=6.63×10(-3)); 5'-adenosine monophosphate-activated protein kinase signalling (P-value=9.57×10(-3)); and apoptosis (P-value=1.75×10(-2)) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status. The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Genome-wide association study of retinopathy in individuals without diabetes.

    Directory of Open Access Journals (Sweden)

    Richard A Jensen

    Full Text Available Mild retinopathy (microaneurysms or dot-blot hemorrhages is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS of mild retinopathy in persons without diabetes.A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy.No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9 on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3±0.23 (beta ± standard error, p = 6.6×10(-9. Evidence suggests this was a false positive finding. The minor allele frequency was low (∼2%, the quality of the imputation was moderate (r(2 ∼0.7, and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension.This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

  11. Association of interleukin-1 family cytokines single nucleotide polymorphisms with susceptibility to systemic sclerosis: an independent case-control study and a meta-analysis.

    Science.gov (United States)

    Huang, Xiao-Lei; Wu, Guo-Cui; Wang, Yu-Jie; Yang, Xiao-Ke; Yang, Guo-Jun; Tao, Jin-Hui; Duan, Yu; Yan, Jun-Wei; Li, Xiang-Pei; Ye, Dong-Qing; Wang, Jing

    2016-08-01

    The aim of our study was to investigate the association of five single nucleotide polymorphisms in interleukin-1 (IL-1) gene with susceptibility to systemic sclerosis (SSc) in a Chinese population. A total of 58 SSc patients and 113 healthy controls were enrolled. TaqMan allele discrimination assay was performed to detect the genotyping of IL-1A -889C/T (rs1800587), IL-1B -511C/T (rs16944), IL-18 -607C/A (rs1946518), IL-18 -137G/C (rs187238) and IL-33 rs7044343. The association between these SNPs and SSc risk was analyzed. Furthermore, a meta-analysis of relevant studies on the association of IL-1A -889C/T (rs1800587) and IL-1B -511C/T (rs16944) with the susceptibility to SSc was performed. Through the genotyping, significant associations for SSc were found for: IL-1A -889C/T genotype frequencies (P = 0.000), dominant model (P = 0.000), recessive model (P = 0.001) and allele T frequency (P = 0.000). Among SSc patients, dyspnea was significantly associated with IL-18 -607C/A genotype frequency and IL-33 rs7044343 allele frequency (P = 0.037, P = 0.042, respectively). In addition, elevated erythrocyte sedimentation rate was significantly associated with IL-18 -137G/C (rs187238) genotype and allele frequency (P = 0.019, P = 0.006, respectively). While meta-analysis showed there was no significant association between IL-1A -889C/T polymorphism and SSc, for IL-1B -511C/T (rs16944), significant associations were found in the comparison of allele C versus T (OR 1.267, 95 % CI 1.016-1.580) by combined different outcomes. Results showed that IL-1A -889C/T (rs1800587) was associated with SSc susceptibility in the Chinese population. However, this association was not supported by a meta-analysis of all relevant studies. Further investigations are required to verify our findings.

  12. Human MTHFR-G1793A transition may be a protective mutation against male infertility: a genetic association study and in silico analysis.

    Science.gov (United States)

    Karimian, Mohammad; Hosseinzadeh Colagar, Abasalt

    2018-06-01

    In this paper, we evaluate the association of the human methylenetetrahydrofolate reductase (MTHFR)-G1793A transition with male infertility using a case-control study, a meta-analysis and an in silico analysis. In the case-control study, 308 blood samples (169 infertile and 139 fertile men) were collected. MTHFR-G1793A genotyping was performed by PCR-RFLP. The study revealed a significant protective association between the GA genotype (OR: 0.3737, 95%CI: 0.1874-0.7452, p = 0.0052) and A allele (OR: 0.4266, 95%CI: 0.2267-0.8030, p = 0.0083) with male infertility. Meta-analysis showed that the G1793A transition might be a protective mutation against male infertility in both A vs. G (OR: 0.608, 95%CI: 0.466-0.792, p silico-analysis revealed that although G1793A could not make fundamental changes in the function and structure of MTHFR, it could modify the structure of the mRNA (Distance =0.1809, p = 0.1095; p < 0.2 is significant). The results suggest that G1793A substitution might be a protective genetic factor against male infertility. However, further case-control studies are required to provide a more robust conclusion.

  13. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies

    NARCIS (Netherlands)

    Nalls, M.A.; Plagnol, V.; Hernandez, D.G.; Sharma, M.; Sheerin, U.M.; Saad, M.; Simon-Sanchez, J.; Schulte, C.; Lesage, S.; Sveinbjornsdottir, S.; Stefansson, K.; Martinez, M.; Hardy, J.; Heutink, P.; Brice, A.; Gasser, T.; Singleton, A.B.; Wood, N.W.; Bloem, B.R.; Post, B.; Scheffer, H.; Warrenburg, B.P.C. van de; et al.,

    2011-01-01

    BACKGROUND: Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease. METHODS: We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA

  14. Association between male pattern baldness and prostate disease: A meta-analysis.

    Science.gov (United States)

    Jin, Tao; Wu, Tao; Luo, Zhumei; Duan, Xi; Deng, Shi; Tang, Yin

    2018-02-01

    Male pattern baldness (MPB) has been associated with an increased risk of prostate cancer (PC) as well as benign prostatic hyperplasia (BPH). We performed a meta-analysis to quantitatively determine the level of risk of PC and BPH in individuals with baldness. A systematic literature search was conducted using several databases. We calculated pooled odds ratios (OR) and 95% CIs. In total, 17 studies comprising 68,448 participants were eligible for the meta-analysis and showed that MPB is associated with an increased risk of aggressive PC (OR = 1.59; 95% CI: 1.36-1.86; Pbaldness and PC (OR = 1.18; 95% CI: 1.05-1.32; P = 0.006). No statistically significant association between vertex, frontal plus vertex hair loss pattern, and BPH were identified. MPB is associated with an increased risk of PC and BPH. Despite our findings, further studies, preferably prospective cohort studies, are required to better elucidate these relationships and to advance knowledge in this field. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. The association between job strain and coronary heart disease: a meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Xu, Shuxian; Huang, Yuli; Xiao, Jiping; Zhu, Wenjing; Wang, Lulu; Tang, Hongfeng; Hu, Yunzhao; Liu, Tiebang

    2015-01-01

    Studies about work stress and the risk of coronary heart disease (CHD) have yielded inconsistent results. This meta-analysis aimed to investigate the association between job strain and the risk of CHD. We searched PubMed and Embase databases for studies reporting data on job strain and the risk of CHD. Studies were included if they reported multiple-adjusted relative risk (RR) with 95% confidence interval (CI) with respect to CHD from job strain. Fourteen prospective cohort studies comprising 232,767 participants were included. The risk of CHD was increased in high-strain (RR 1.26; 95% CI 1.12-1.41) and passive jobs (RR 1.14; 95% CI 1.02-1.29) but not in active jobs (RR 1.09; 95% CI 0.97-1.22), when compared with low-strain group. The increased risk of CHD in high-strain and passive jobs was mainly driven by studies with a follow-up duration of ≥ 10 years. Neither the low-control (RR 1.06; 95% CI 0.93-1.19) nor high-demand (RR 1.13; 95% CI 0.97-1.32) dimension was independently associated with the risk of CHD. Individuals with high-strain and passive jobs were more likely to experience a CHD event. Intervention programs incorporating individual and organizational levels are crucial for reducing job strain and the risk of CHD.

  16. Genome-wide association study identifies novel locus for neuroticism and shows polygenic association with Major Depressive Disorder

    Science.gov (United States)

    de Moor, Marleen H.M.; van den Berg, Stéphanie M.; Verweij, Karin J.H.; Krueger, Robert F.; Luciano, Michelle; Vasquez, Alejandro Arias; Matteson, Lindsay K.; Derringer, Jaime; Esko, Tõnu; Amin, Najaf; Gordon, Scott D.; Hansell, Narelle K.; Hart, Amy B.; Seppälä, Ilkka; Huffman, Jennifer E.; Konte, Bettina; Lahti, Jari; Lee, Minyoung; Miller, Mike; Nutile, Teresa; Tanaka, Toshiko; Teumer, Alexander; Viktorin, Alexander; Wedenoja, Juho; Abecasis, Goncalo R.; Adkins, Daniel E.; Agrawal, Arpana; Allik, Jüri; Appel, Katja; Bigdeli, Timothy B.; Busonero, Fabio; Campbell, Harry; Costa, Paul T.; Smith, George Davey; Davies, Gail; de Wit, Harriet; Ding, Jun; Engelhardt, Barbara E.; Eriksson, Johan G.; Fedko, Iryna O.; Ferrucci, Luigi; Franke, Barbara; Giegling, Ina; Grucza, Richard; Hartmann, Annette M.; Heath, Andrew C.; Heinonen, Kati; Henders, Anjali K.; Homuth, Georg; Hottenga, Jouke-Jan; Janzing, Joost; Jokela, Markus; Karlsson, Robert; Kemp, John P.; Kirkpatrick, Matthew G.; Latvala, Antti; Lehtimäki, Terho; Liewald, David C.; Madden, Pamela A.F.; Magri, Chiara; Magnusson, Patrik K.E.; Marten, Jonathan; Maschio, Andrea; Medland, Sarah E.; Mihailov, Evelin; Milaneschi, Yuri; Montgomery, Grant W.; Nauck, Matthias; Ouwens, Klaasjan G.; Palotie, Aarno; Pettersson, Erik; Polasek, Ozren; Qian, Yong; Pulkki-Råback, Laura; Raitakari, Olli T.; Realo, Anu; Rose, Richard J.; Ruggiero, Daniela; Schmidt, Carsten O.; Slutske, Wendy S.; Sorice, Rossella; Starr, John M.; Pourcain, Beate St; Sutin, Angelina R.; Timpson, Nicholas J.; Trochet, Holly; Vermeulen, Sita; Vuoksimaa, Eero; Widen, Elisabeth; Wouda, Jasper; Wright, Margaret J.; Zgaga, Lina; Scotland, Generation; Porteous, David; Minelli, Alessandra; Palmer, Abraham A.; Rujescu, Dan; Ciullo, Marina; Hayward, Caroline; Rudan, Igor; Metspalu, Andres; Kaprio, Jaakko; Deary, Ian J.; Räikkönen, Katri; Wilson, James F.; Keltikangas-Järvinen, Liisa; Bierut, Laura J.; Hettema, John M.; Grabe, Hans J.; van Duijn, Cornelia M.; Evans, David M.; Schlessinger, David; Pedersen, Nancy L.; Terracciano, Antonio; McGue, Matt; Penninx, Brenda W.J.H.; Martin, Nicholas G.; Boomsma, Dorret I.

    2015-01-01

    Importance Neuroticism is a personality trait that is briefly defined by emotional instability. It is a robust genetic risk factor for Major Depressive Disorder (MDD) and other psychiatric disorders. Hence, neuroticism is an important phenotype for psychiatric genetics. The Genetics of Personality Consortium (GPC) has created a resource for genome-wide association analyses of personality traits in over 63,000 participants (including MDD cases). Objective To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association (GWA) results based on 1000Genomes imputation, to evaluate if common genetic variants as assessed by Single Nucleotide Polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability, and to examine whether SNPs that predict neuroticism also predict MDD. Setting 30 cohorts with genome-wide genotype, personality and MDD data from the GPC. Participants The study included 63,661 participants from 29 discovery cohorts and 9,786 participants from a replication cohort. Participants came from Europe, the United States or Australia. Main outcome measure(s) Neuroticism scores harmonized across all cohorts by Item Response Theory (IRT) analysis, and clinically assessed MDD case-control status. Results A genome-wide significant SNP was found in the MAGI1 gene (rs35855737; P=9.26 × 10−9 in the discovery meta-analysis, and P=2.38 × 10−8 in the meta-analysis of all 30 cohorts). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 of the discovery cohorts significantly predicted neuroticism in 2 independent cohorts. Importantly, polygenic scores also predicted MDD in these cohorts. Conclusions and relevance This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study

  17. Powerful Tests for Multi-Marker Association Analysis Using Ensemble Learning.

    Directory of Open Access Journals (Sweden)

    Badri Padhukasahasram

    Full Text Available Multi-marker approaches have received a lot of attention recently in genome wide association studies and can enhance power to detect new associations under certain conditions. Gene-, gene-set- and pathway-based association tests are increasingly being viewed as useful supplements to the more widely used single marker association analysis which have successfully uncovered numerous disease variants. A major drawback of single-marker based methods is that they do not look at the joint effects of multiple genetic variants which individually may have weak or moderate signals. Here, we describe novel tests for multi-marker association analyses that are based on phenotype predictions obtained from machine learning algorithms. Instead of assuming a linear or logistic regression model, we propose the use of ensembles of diverse machine learning algorithms for prediction. We show that phenotype predictions obtained from ensemble learning algorithms provide a new framework for multi-marker association analysis. They can be used for constructing tests for the joint association of multiple variants, adjusting for covariates and testing for the presence of interactions. To demonstrate the power and utility of this new approach, we first apply our method to simulated SNP datasets. We show that the proposed method has the correct Type-1 error rates and can be considerably more powerful than alternative approaches in some situations. Then, we apply our method to previously studied asthma-related genes in 2 independent asthma cohorts to conduct association tests.

  18. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits

    DEFF Research Database (Denmark)

    Speliotes, Elizabeth K; Yerges-Armstrong, Laura M; Wu, Jun

    2011-01-01

    steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (~26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n¿=¿880 to 3,070). By carrying out a fixed-effects meta......-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ~2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome......Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic...

  19. Genome-wide association study and biological pathway analysis of the Eimeria maxima response in broilers.

    Science.gov (United States)

    Hamzić, Edin; Buitenhuis, Bart; Hérault, Frédéric; Hawken, Rachel; Abrahamsen, Mitchel S; Servin, Bertrand; Elsen, Jean-Michel; Pinard-van der Laan, Marie-Hélène; Bed'Hom, Bertrand

    2015-11-25

    Coccidiosis is the most common and costly disease in the poultry industry and is caused by protozoans of the Eimeria genus. The current control of coccidiosis, based on the use of anticoccidial drugs and vaccination, faces serious obstacles such as drug resistance and the high costs for the development of efficient vaccines, respectively. Therefore, the current control programs must be expanded with complementary approaches such as the use of genetics to improve the host response to Eimeria infections. Recently, we have performed a large-scale challenge study on Cobb500 broilers using E. maxima for which we investigated variability among animals in response to the challenge. As a follow-up to this challenge study, we performed a genome-wide association study (GWAS) to identify genomic regions underlying variability of the measured traits in the response to Eimeria maxima in broilers. Furthermore, we conducted a post-GWAS functional analysis to increase our biological understanding of the underlying response to Eimeria maxima challenge. In total, we identified 22 single nucleotide polymorphisms (SNPs) with q value Eimeria maxima in broilers. Furthermore, the post-GWAS functional analysis indicates that biological pathways and networks involved in tissue proliferation and repair along with the primary innate immune response may play the most important role during the early stage of Eimeria maxima infection in broilers.

  20. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies

    NARCIS (Netherlands)

    Nalls, Michael A.; Plagnol, Vincent; Hernandez, Dena G.; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simon-Sanchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjornsdottir, Sigurlaug; Arepalli, Sampath; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M. A.; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, J. Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-Francois; Deloukas, Panos; Deuschl, Guenther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Duerr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gibbs, J. Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gustafsson, Omar; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jonsson, Palmi V.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R.; Morrison, Karen E.; Mudanohwo, Ese; O'Sullivan, Sean S.; Pearson, Justin; Perlmutter, Joel S.; Petursson, Hjoervar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C. A.; Stefansson, Hreinn; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, Francois; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, Andre G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Stefansson, Kari; Martinez, Maria; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Singleton, Andrew B.; Wood, Nicholas W.

    2011-01-01

    Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease. Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and

  1. Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis

    Science.gov (United States)

    2014-01-01

    Background Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk. Methods Eligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score. Results Eighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR). Conclusions Our meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings. PMID:24428862

  2. Meta-analysis of association between the TP53 Arg72Pro polymorphism and risk of endometriosis based on case-control studies.

    Science.gov (United States)

    Yan, Yulan; Wu, Renzheng; Li, Shaojing; He, Jinlong

    2015-06-01

    In the light of the relationship between the TP53 Arg72Pro (rs1042522) polymorphism and the risk of endometriosis remains inclusive or controversial. For better understanding of the effect of TP53 Arg72Pro polymorphism on endometriosis risk, we performed a meta-analysis. The relevant studies were identified through a search of PubMed, Web of Science, EMBASE, Ovid, Springer, China National Knowledge Infrastructure (CNKI), cqvip, Wanfang database, and Chinese Biomedical Literature (CBM) databases up to December, 2014. The association between the TP53 Arg72Pro polymorphism and endometriosis risk was pooled by conducted by odds ratios and 95% confidence intervals. A total of fifteen case-control studies with 2683 cases and 3335 controls were eventually identified. There was significant association between Arg72Pro polymorphism and endometriosis risk in all of the five models in overall populations (C vs. G: OR=1.32, 95%CI=1.14-1.53, p=0.00; CC vs. GG: OR=1.80, 95%CI=1.28-2.53, p=0.001; GC vs. GG: OR=1.52, 95%CI=1.22-1.88, p=0.00; CC vs. OR=1.32, 95%CI=1.05-1.66, p=0.016; CC/GC vs. GG: OR=1.59, 95%CI=1.26-2.00, p=0.00). In the sub-group analysis according to ethnicity, the results suggested that TP53 Arg72Pro polymorphism was not associated with endometriosis risk in Caucasians. However, the significant association was found in Asians and Mixed race (MIX) under the five models. The results of this meta-analysis suggest that the TP53 Arg72Pro polymorphism can increase the risk of endometriosis, especially among Asians and MIX populations. Considering the limited sample size and ethnicities included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Association of thrombophilia and catheter-associated thrombosis in children: a systematic review and meta-analysis.

    Science.gov (United States)

    Neshat-Vahid, S; Pierce, R; Hersey, D; Raffini, L J; Faustino, E V S

    2016-09-01

    Essentials It is unclear if thrombophilia increases the risk of catheter-associated thrombosis in children. We conducted a meta-analysis on thrombophilia and pediatric catheter-associated thrombosis. Presence of ≥1 trait confers additional risk of venous thrombosis in children with catheters. Limitations of included studies preclude us from recommending routine thrombophilia testing. Background The association between thrombophilia and deep vein thrombosis (DVT) associated with central venous catheter (CVC) use, the most important pediatric risk factor for thrombosis, is unclear in children. Pediatric studies with small sample sizes have reported conflicting results. We sought to evaluate whether, among children with CVCs, thrombophilia increases the risk of CVC-associated DVT (CADVT). Materials and methods We systematically searched MEDLINE, EMBASE, the Web of Science, the Cochrane Central Register for Controlled Trials, PubMed and reference lists for controlled studies published from the inception of the database until September 2015. Included were studies of children aged levels and the FV Leiden mutation had an increased prevalence of CADVT. The association with thrombophilia seemed to be stronger for symptomatic CADVT (pOR 6.71; 95% CI 1.93-23.37) than for asymptomatic CADVT (pOR 2.14; 95% CI 1.10-4.18). Conclusions On the basis of the low prevalence of specific traits, the relatively weak association with CADVT, and the limitations of the included studies, we cannot recommend routine testing of thrombophilias in children with CADVT. © 2016 International Society on Thrombosis and Haemostasis.

  4. Association between periodontitis and ischemic stroke: a systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Leira, Yago; Seoane, Juan; Blanco, Miguel; Rodríguez-Yáñez, Manuel; Takkouche, Bahi; Blanco, Juan; Castillo, José

    2017-01-01

    Several observational studies have suggested an association between periodontitis and cerebral ischemia. This meta-analysis aimed to investigate whether this link exists, and if so, the degree to which it is significant. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline for systematic review was used. The search strategy included using electronic databases and hand searching works published up to March 2015. MEDLINE via PubMed, EMBASE, Proceedings Web of Science and Current Contents Connect were searched by two independent reviewers. Case-control, cross-sectional or cohort studies including patients with measures of periodontitis and ischemic stroke were eligible to be included in the analysis. Quality assessments of selected studies were performed. From a total of 414 titles and abstracts, 57 potentially relevant full text papers were identified. After inclusion criteria were applied, 8 studies were included in the present systematic review (5 case-control and 3 cohort studies). Although it was not the intention, cross-sectional studies were excluded due to eligibility criteria were not accomplished. Therefore, meta-analyses were conducted with data retrieved from the 8 studies included. These meta-analyses showed statistically significant association between periodontitis and ischemic stroke in both cohort pooled relative risks at 2.52 (1.77–3.58), and case-control studies pooled relative risks at 3.04 (1.10–8.43). In conclusion, the present meta-analysis demonstrated an association between periodontitis and ischemic stroke. However, well-designed prospective studies should be carried out to provide robust evidence of the link between both diseases. In regards to ischemic stroke subtypes, further case-control studies should be carried out to investigate whether there is any association between the different subtypes of cerebral infarcts and periodontitis.

  5. Guidance for the utility of linear models in meta-analysis of genetic association studies of binary phenotypes.

    Science.gov (United States)

    Cook, James P; Mahajan, Anubha; Morris, Andrew P

    2017-02-01

    Linear mixed models are increasingly used for the analysis of genome-wide association studies (GWAS) of binary phenotypes because they can efficiently and robustly account for population stratification and relatedness through inclusion of random effects for a genetic relationship matrix. However, the utility of linear (mixed) models in the context of meta-analysis of GWAS of binary phenotypes has not been previously explored. In this investigation, we present simulations to compare the performance of linear and logistic regression models under alternative weighting schemes in a fixed-effects meta-analysis framework, considering designs that incorporate variable case-control imbalance, confounding factors and population stratification. Our results demonstrate that linear models can be used for meta-analysis of GWAS of binary phenotypes, without loss of power, even in the presence of extreme case-control imbalance, provided that one of the following schemes is used: (i) effective sample size weighting of Z-scores or (ii) inverse-variance weighting of allelic effect sizes after conversion onto the log-odds scale. Our conclusions thus provide essential recommendations for the development of robust protocols for meta-analysis of binary phenotypes with linear models.

  6. A genomic background based method for association analysis in related individuals.

    Directory of Open Access Journals (Sweden)

    Najaf Amin

    Full Text Available BACKGROUND: Feasibility of genotyping of hundreds and thousands of single nucleotide polymorphisms (SNPs in thousands of study subjects have triggered the need for fast, powerful, and reliable methods for genome-wide association analysis. Here we consider a situation when study participants are genetically related (e.g. due to systematic sampling of families or because a study was performed in a genetically isolated population. Of the available methods that account for relatedness, the Measured Genotype (MG approach is considered the 'gold standard'. However, MG is not efficient with respect to time taken for the analysis of genome-wide data. In this context we proposed a fast two-step method called Genome-wide Association using Mixed Model and Regression (GRAMMAR for the analysis of pedigree-based quantitative traits. This method certainly overcomes the drawback of time limitation of the measured genotype (MG approach, but pays in power. One of the major drawbacks of both MG and GRAMMAR, is that they crucially depend on the availability of complete and correct pedigree data, which is rarely available. METHODOLOGY: In this study we first explore type 1 error and relative power of MG, GRAMMAR, and Genomic Control (GC approaches for genetic association analysis. Secondly, we propose an extension to GRAMMAR i.e. GRAMMAR-GC. Finally, we propose application of GRAMMAR-GC using the kinship matrix estimated through genomic marker data, instead of (possibly missing and/or incorrect genealogy. CONCLUSION: Through simulations we show that MG approach maintains high power across a range of heritabilities and possible pedigree structures, and always outperforms other contemporary methods. We also show that the power of our proposed GRAMMAR-GC approaches to that of the 'gold standard' MG for all models and pedigrees studied. We show that this method is both feasible and powerful and has correct type 1 error in the context of genome-wide association analysis

  7. Significant association between asthma risk and the GSTM1 and GSTT1 deletion polymorphisms: an updated meta-analysis of case-control studies.

    Science.gov (United States)

    Liang, Siqiao; Wei, Xuan; Gong, Chen; Wei, Jinmei; Chen, Zhangrong; Chen, Xiaoli; Wang, Zhibo; Deng, Jingmin

    2013-07-01

    Polymorphisms in GSTM1 and GSTT1 may be associated with asthma risk, yet several studies and meta-analyses have reported inconclusive results. Therefore, an updated meta-analysis was conducted. Literature searches were performed using the Pubmed, Embase and Web of Science databases until October 2012. Variant 'null' genotype was compared with wild-type 'present' in the pooled data. All statistical analyses were performed using STATA 11.0. A total of 26 case-control studies were suitable for inclusion in the meta-analysis. In the overall population, a significant association was found for both the GSTM1 (odds ratio (OR) = 1.452; 95% confidence interval (CI): 1.192-1.770) and GSTT1 polymorphism (OR = 1.792; 95% CI:1.293-2.483). For subgroup analysis by age, GSTM1 significantly increased risk for both children (OR = 1.368; 95% CI: 1.051-1.781) and adults (OR = 1.859; 95% CI: 1.183-2.921). For GSTT1, a significant association was only found in the adult population (OR = 2.312; 95%CI: 1.204-4.439). Based on subgroup analysis by ethnicity, a significant association for GSTM1 was found in Europe (OR = 1.303; 95% CI: 1.018-1.667), Africa (OR = 2.175; 95%CI: 1.560-3.031) and Latin America (OR = 2.265; 95%CI: 1.375-3.729). For GSTT1, significantly increased risk was found only for Asian (OR = 2.105; 95% CI: 1.101-4.025) and Russian (OR = 2.747; 95% CI: 1.071-7.046) populations. This meta-analysis provides evidence that GSTM1 and GSTT1 polymorphisms may be risk factors for asthma. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  8. Association between the p53 codon 72 polymorphism and primary open-angle glaucoma risk: Meta-analysis based on 11 case–control studies

    Directory of Open Access Journals (Sweden)

    Mohsen Gohari

    2016-01-01

    Full Text Available The TP53 is important in functions of cell cycle control, apoptosis, and maintenance of DNA integrity. Studies on the association between p53 codon 72 polymorphism and primary open-angle glaucoma (POAG risk have yielded conflicting results. Published literature from PubMed and Web of Science databases was retrieved. All studies evaluating the association between p53 codon 72 polymorphisms and POAG were included. Pooled odds ratio (OR and 95% confidence interval (CI were calculated. Eleven separate studies including 2541 cases and 1844 controls were pooled in the meta-analysis. We did not detect a significant association between POAG risk and p53 codon 72 polymorphism overall population except allele genetic model (C vs. G: OR = 0.961, 95% CI = 0.961–0.820, P = 0.622. In the stratified analysis for Asians and Caucasians, there was an association between p53 codon 72 polymorphism and POAG. In the dominant model in the overall population and by ethnicity subgroups, the highest elevated POAG risk was presented. In summary, these results indicate that p53 codon 72 polymorphism is likely an important genetic factor contributing to susceptibility of POAG. However, more case–controls studies based on larger sample size and stratified by ethnicity are suggested to further clarify the relationship between p53 codon 72 polymorphism and POAG.

  9. Genome-wide association study of antisocial personality disorder.

    Science.gov (United States)

    Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

    2016-09-06

    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53-3.14), P=1.9 × 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37-1.85), P=1.6 × 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.

  10. Genome-wide association study of antisocial personality disorder

    Science.gov (United States)

    Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

    2016-01-01

    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53–3.14), P=1.9 × 10-5). Two polymorphisms at 6p21.2 LINC00951–LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37–1.85), P=1.6 × 10−9) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder. PMID:27598967

  11. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies

    DEFF Research Database (Denmark)

    Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L

    2011-01-01

    Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.......Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors....

  12. Association of XPC polymorphisms and lung cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Bo Jin

    Full Text Available BACKGROUND: Xeroderma pigmentosum complementation group C gene (XPC is a key member of nucleotide excision repair pathway and plays an important role in human DNA repair system. It is reported that several common polymorphisms of XPC are associated with susceptibility to lung cancer. However, the conclusion is still elusive. METHOD: This meta-analysis was performed to determine the relationship between XPC polymorphisms (Lys939Gln, Ala499Val, and PAT and lung cancer risk. Published literatures were identified by searching online databases and reference lists of relevant studies. Odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the association strength. Publication bias were detected by Egger's and Begg's test. RESULT: After strict screening, we identified 14 eligible studies in this meta-analysis, including 5647 lung cancer cases and 6908 controls. By pooling all eligible studies, we found that the homozygote Gln939Gln genotype was associated with a significantly increased risk of lung cancer in Asian population (GlnGln vs LysLys, OR=1.229, 95% CI: 1.000-1.510; GlnGln vs LysLys/LysGln, OR=1.257, 95% CI: 1.038-1.522. As for the PAT polymorphism, in Caucasian population, we found carriers of the -/- genotype were associated significantly reduced risk of lung cancer in homozygote comparison model (-/- vs +/+, OR=0.735, 95% CI: 0.567-0.952. CONCLUSION: In this meta-analysis we found that Gln939Gln genotype was associated with significantly increased risk of lung cancer in Asian population; the PAT -/- genotype significantly reduced susceptibility to lung cancer in Caucasian population; while the XPC Ala499Val polymorphism was not associated with lung cancer risk.

  13. Association of Human Methionine Synthase-A2756G Transition With Prostate Cancer: A Case-Control Study and in Silico Analysis

    Directory of Open Access Journals (Sweden)

    Arezou Ebrahimi

    2017-07-01

    Full Text Available Methionine synthase (MTR is one of the key enzymes of folate pathway, which play a key role in the construction, repair, and methylation of DNA. In this study, an association of MTR A2756G gene transition with prostate cancer in men populations of Kashan-Iran was investigated by a case-control study and an in silico analysis. The 200 samples including 100 patients with prostate cancer, as case group and 100 healthy men, as control group included in this study. MTR-A2756G genotyping was performed by PCR-RFLP technique. Some in silico tools used to evaluate the effects of A2756G transition on the structure and function of MTR. Results showed that the AG genotype (OR: 2.4014, 95% CI: 1.3216-4.3636, P=0.0040, and GG genotype (OR: 3.6324, 95% CI: 1.2629-10.4475, P=0.0167 and G allele (OR: 2.0120, 95% CI: 1.3098-3.0905, P=0.0014 were associated with prostate cancer. In silico analysis showed that polymorphisms of the enzyme protein might change properties of MTR such as relative mutability and flexibility, which leads to alteration of stability and function of the enzyme. Based on the results, an MTR-A2756G polymorphism which changes activity and stability of the methionine synthase associated with prostate cancer in men. It is a preliminary study and is presenting data for future comprehensive study for making a clinical conclusion that this gene transition is a biomarker for susceptibility to prostate cancer.

  14. Association Analysis of FOXO3 Longevity Variants With Blood Pressure and Essential Hypertension.

    Science.gov (United States)

    Morris, Brian J; Chen, Randi; Donlon, Timothy A; Evans, Daniel S; Tranah, Gregory J; Parimi, Neeta; Ehret, Georg B; Newton-Cheh, Christopher; Seto, Todd; Willcox, D Craig; Masaki, Kamal H; Kamide, Kei; Ryuno, Hirochika; Oguro, Ryosuke; Nakama, Chikako; Kabayama, Mai; Yamamoto, Koichi; Sugimoto, Ken; Ikebe, Kazunori; Masui, Yukie; Arai, Yasumichi; Ishizaki, Tatsuro; Gondo, Yasuyuki; Rakugi, Hiromi; Willcox, Bradley J

    2016-11-01

    The minor alleles of 3 FOXO3 single nucleotide polymorphisms (SNPs)- rs2802292 , rs2253310 , and rs2802288 -are associated with human longevity. The aim of the present study was to test these SNPs for association with blood pressure (BP) and essential hypertension (EHT). In a primary study involving Americans of Japanese ancestry drawn from the Family Blood Pressure Program II we genotyped 411 female and 432 male subjects aged 40-79 years and tested for statistical association by contingency table analysis and generalized linear models that included logistic regression adjusting for sibling correlation in the data set. Replication of rs2802292 with EHT was attempted in Japanese SONIC study subjects and of each SNP in a meta-analysis of genome-wide association studies of BP in individuals of European ancestry. In Americans of Japanese ancestry, women homozygous for the longevity-associated (minor) allele of each FOXO3 SNP had 6mm Hg lower systolic BP and 3mm Hg lower diastolic BP compared with major allele homozygotes (Bonferroni corrected P 0.05, respectively). Frequencies of minor allele homozygotes were 3.3-3.9% in women with EHT compared with 9.5-9.6% in normotensive women ( P = 0.03-0.04; haplotype analysis P = 0.0002). No association with BP or EHT was evident in males. An association with EHT was seen for the minor allele of rs2802292 in the Japanese SONIC cohort ( P = 0.03), while in European subjects the minor allele of each SNP was associated with higher systolic and diastolic BP. Longevity-associated FOXO3 variants may be associated with lower BP and EHT in Japanese women.

  15. Meta-analysis: Association of Helicobacter pylori infection with Parkinson's diseases.

    Science.gov (United States)

    Shen, Xiaoli; Yang, Huazhen; Wu, Yili; Zhang, Dongfeng; Jiang, Hong

    2017-10-01

    The results from observational studies on the relationship between helicobacter pylori (H. pylori) infection and Parkinson's disease remain controversial. A meta-analysis was conducted to evaluate the association between helicobacter pylori infection and Parkinson's disease. A comprehensive literature search was performed on relevant studies published from January 1983 to January 2017 in PubMed, Web of Science and EMBASE databases. The fixed or random effects model was used to pool the odds ratio with 95% confidence interval from individual studies. Publication bias was estimated by Egger's test and the funnel plot. Eight eligible studies involving 33 125 participants were included in this meta-analysis. Compared with the no helicobacter pylori infected person, the pooled odds ratio of Parkinson's disease in helicobacter pylori infected person was 1.59 (95% confidence interval: 1.37-1.85). In subgroup analyzes, the combined odds ratios were 1.96 (1.23-3.12) in Asia, 1.55 (1.32-1.82) in Europe, 1.59 (1.35-1.88) in case-control studies, 1.56 (1.01-2.39) in cross-sectional studies, 1.56 (1.32-1.85) in studies with confounders adjusted, and 1.71 (1.21-2.43) in studies with no confounder adjusted, respectively. This meta-analysis indicated that H. pylori infection might be associated with the risk of Parkinson's disease. © 2017 John Wiley & Sons Ltd.

  16. Prothrombin G20210A mutation is associated with young-onset stroke: the genetics of early-onset stroke study and meta-analysis.

    Science.gov (United States)

    Jiang, Baijia; Ryan, Kathleen A; Hamedani, Ali; Cheng, Yuching; Sparks, Mary J; Koontz, Deborah; Bean, Christopher J; Gallagher, Margaret; Hooper, W Craig; McArdle, Patrick F; O'Connell, Jeffrey R; Stine, O Colin; Wozniak, Marcella A; Stern, Barney J; Mitchell, Braxton D; Kittner, Steven J; Cole, John W

    2014-04-01

    Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a white case-control population and additionally performed a meta-analysis. From the population-based Genetics of Early Onset Stroke (GEOS) study, we identified 397 individuals of European ancestry aged 15 to 49 years with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios (ORs) in the entire population and for subgroups stratified by sex, age, oral contraceptive use, migraine, and smoking status. A meta-analysis of 17 case-control studies (n=2305 cases ischemic stroke did not achieve statistical significance (OR=2.5; 95% confidence interval [CI]=0.9-6.5; P=0.07). However, among adults aged 15 to 42 years (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9; 95% CI=1.2-28.1; P=0.03), whereas adults aged 42 to 49 years were not (OR=1.4; 95% CI=0.4-5.1; P=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults ≤55 years (OR=1.4; 95% CI=1.1-1.9; P=0.02), with significance increasing with addition of the GEOS results (OR=1.5; 95% CI=1.1-2.0; P=0.005). The prothrombin G20210A mutation is associated with ischemic stroke in young adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger young adult population requires replication.

  17. Association of atrial fibrillation and cancer: Analysis from two large population-based case-control studies.

    Science.gov (United States)

    Saliba, Walid; Rennert, Hedy S; Gronich, Naomi; Gruber, Stephen B; Rennert, Gad

    2018-01-01

    An association between atrial fibrillation (AF) and risk of cancer has been suggested in several studies, including prospective cohort studies. However, the magnitude and the temporal nature of this association remain unclear. Data from two large prospective population-based case-control studies, the Molecular Epidemiology of Colorectal Cancer (MECC, n = 8,383) and the Breast Cancer in Northern Israel Study (BCINIS, n = 11,608), were used to better understand the nature and temporality of a possible association between cancer diagnosis and AF events before and after cancer diagnosis. A case-control study approach was employed to study prior AF as a risk factor for cancer, and a cohort study approach was employed to study incident cancer as a risk factor for AF. AF was associated with a significant reduced odds of cancer as reflected in the case-control approach, with an adjusted OR = 0.77 (95% CI, 0.65-0.91), while cancer was not found to be significantly associated with elevated risk of AF in the cohort approach, with an adjusted HR = 1.10 (0.98-1.23). The immediate period (90 days) after an AF event was associated with a 1.85 times increased risk of cancer, and the immediate period after the diagnosis of cancer was associated with a 3.4 fold increased risk of AF. These findings probably reflect both the effect of acute transient conditions associated with new cancer diagnosis and detection bias. Similar results were identified with colorectal and breast cancer cases. Atrial fibrillation of longer than 90 days duration is associated with reduced odds of new cancer diagnosis. The results of this study suggest that an association observed in prior research may be due to instances related to cancer diagnosis and detection bias rather than a causal relationship. However, there may be bias in the sampling and residual confounding that distort the associations.

  18. GENIE: a software package for gene-gene interaction analysis in genetic association studies using multiple GPU or CPU cores

    Directory of Open Access Journals (Sweden)

    Wang Kai

    2011-05-01

    Full Text Available Abstract Background Gene-gene interaction in genetic association studies is computationally intensive when a large number of SNPs are involved. Most of the latest Central Processing Units (CPUs have multiple cores, whereas Graphics Processing Units (GPUs also have hundreds of cores and have been recently used to implement faster scientific software. However, currently there are no genetic analysis software packages that allow users to fully utilize the computing power of these multi-core devices for genetic interaction analysis for binary traits. Findings Here we present a novel software package GENIE, which utilizes the power of multiple GPU or CPU processor cores to parallelize the interaction analysis. GENIE reads an entire genetic association study dataset into memory and partitions the dataset into fragments with non-overlapping sets of SNPs. For each fragment, GENIE analyzes: 1 the interaction of SNPs within it in parallel, and 2 the interaction between the SNPs of the current fragment and other fragments in parallel. We tested GENIE on a large-scale candidate gene study on high-density lipoprotein cholesterol. Using an NVIDIA Tesla C1060 graphics card, the GPU mode of GENIE achieves a speedup of 27 times over its single-core CPU mode run. Conclusions GENIE is open-source, economical, user-friendly, and scalable. Since the computing power and memory capacity of graphics cards are increasing rapidly while their cost is going down, we anticipate that GENIE will achieve greater speedups with faster GPU cards. Documentation, source code, and precompiled binaries can be downloaded from http://www.cceb.upenn.edu/~mli/software/GENIE/.

  19. Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Ji-Ming Bao

    2014-06-01

    Full Text Available Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs and 95% confidence intervals (CIs were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10-1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10-1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43, P= 0.003, respectively. Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33-1.79, P < 0.001; OR = 1.38, 95% CI = 1.15-1.66, P= 0.001; and OR = 1.39, 95% CI = 1.15-1.67, P= 0.001, but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

  20. Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis.

    Science.gov (United States)

    Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

    2014-01-01

    Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10-1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10-1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43, P= 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33-1.79, P < 0.001; OR = 1.38, 95% CI = 1.15-1.66, P= 0.001; and OR = 1.39, 95% CI = 1.15-1.67, P= 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

  1. Association between increase in fixed penalties and road safety outcomes: A meta-analysis.

    Science.gov (United States)

    Elvik, Rune

    2016-07-01

    Studies that have evaluated the association between increases in traffic fine amounts (fixed penalties) and changes in compliance with road traffic law or the number of accidents are synthesised by means of meta-analysis. The studies were few and different in many respects. Nine studies were included in the meta-analysis of changes in compliance. Four studies were included in the meta-analysis of changes in accidents. Increasing traffic fines was found to be associated with small changes in the rate of violations. The changes were non-linear. For increases up to about 100%, violations were reduced. For larger increases, no reduction in violations was found. A small reduction in fatal accidents was associated with increased fixed penalties, varying between studies from less than 1-12%. The main pattern of changes in violations was similar in the fixed-effects and random-effects models of meta-analysis, meta-regression and when simple (non-weighted) mean values were computed. The main findings are thus robust, although most of the primary studies did not control very well for potentially confounding factors. Summary estimates of changes in violations or accidents should be treated as provisional and do not necessarily reflect causal relationships. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Polymorphism of the FABP2 gene: a population frequency analysis and an association study with cardiovascular risk markers in Argentina

    Directory of Open Access Journals (Sweden)

    Mayorga Luis S

    2007-06-01

    Full Text Available Abstract Background The FABP2 gene encodes for the intestinal FABP (IFABP protein, which is expressed only in intestinal enterocytes. A polymorphism at codon 54 in exon 2 of the FABP2 gene exchanges an Alanine (Ala, in the small helical region of the protein, for Threonine (Thr. Given the potential physiological role of the Ala54Thr FABP2 polymorphism, we assess in this study the local population frequency and analyze possible associations with five selected markers, i.e. glycemia, total cholesterol, body mass index (BMI, hypertension, and high Cardiovascular Risk Index (CVR index. Methods We studied 86 men and 116 women. DNA was extracted from a blood drop for genotype analysis. Allele frequencies were calculated by direct counting. Hardy Weinberg Equilibrium was evaluated using a Chi-square goodness of fit test. For the polymorphism association analysis, five markers were selected, i.e. blood pressure, Framingham Risk Index, total cholesterol, BMI, and glycemia. For each marker, the Odds Ratio (OR was calculated by an online statistic tool. Results Our results reveal a similar population polymorphism frequency as in previous European studies, with q = 0.277 (95% confidence limits 0.234–0.323. No significant association was found with any of the tested markers in the context of our Argentine nutritional and cultural habits. We did, however, observe a tendency for increased Cholesterol and high BMI in Thr54 carriers. Conclusion This is the first study to look at the population frequency of the Thr54 allele in Argentina. The obtained result does not differ from previously reported frequencies in European populations. Moreover, we found no association between the Thr54 allele and any of the five selected markers. The observed tendency to increased total cholesterol and elevated BMI in Thr54 carriers, even though not significant for p

  3. Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Satoru Kodama

    2018-01-01

    Full Text Available Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM using several single nucleotide polymorphisms (SNPs based on findings of genome-wide association studies (GWAS. However, the quantitative association of cumulative risk alleles (RAs of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR of T2DM for 1 increment in RAs carried (1-ΔRA in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13–1.19. In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08–1.13. There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies. The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies. The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution.

  4. Steep Delay Discounting and Addictive Behavior: A Meta-Analysis of Continuous Associations

    Science.gov (United States)

    Amlung, Michael; Vedelago, Lana; Acker, John; Balodis, Iris; MacKillop, James

    2016-01-01

    Aims To synthesize continuous associations between delayed reward discounting (DRD) and both addiction severity and quantity-frequency (QF); to examine moderators of these relationships; and to investigate publication bias. Methods Meta-analysis of published studies examining continuous associations between DRD and addictive behaviors. Published, peer-reviewed studies on addictive behaviors (alcohol, tobacco, cannabis, stimulants, opiates, and gambling) were identified via PubMed, MEDLINE, and PsycInfo. Studies were restricted to DRD measures of monetary gains. Random effects meta-analysis was conducted using Pearson’s r as the effect size. Publication bias was evaluated using fail-safe N, Begg-Mazumdar and Egger’s tests, meta-regression of publication year and effect size, and imputation of missing studies. Results The primary meta-analysis revealed a small magnitude effect size that was highly significant (r = 0.14, p addictive behavior (p = 0.30) or DRD assessment (p = 0.90). Indices of publication bias suggested a modest impact of unpublished findings. Conclusions Delayed reward discounting is robustly associated with continuous measures of addiction severity and quantity-frequency. This relation is generally robust across type of addictive behavior and delayed reward discounting assessment modality. PMID:27450931

  5. Strong association of 677 C>T substitution in the MTHFR gene with male infertility--a study on an indian population and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Nishi Gupta

    Full Text Available Methylenetetrahydrofolate reductase (MTHFR is an important enzyme of folate and methionine metabolism, making it crucial for DNA synthesis and methylation. The objective of this study was to analyze MTHFR gene 677C>T polymorphism in infertile male individuals from North India, followed by a meta-analysis on our data and published studies.We undertook genotyping on a total of 837 individuals including well characterized infertile (N = 522 and confirmed fertile (N = 315 individuals. The SNP was typed by direct DNA sequencing. Chi square test was done for statistical analysis. Published studies were searched using appropriate keywords. Source of data collection for meta-analysis included 'Pubmed', 'Ovid' and 'Google Scholar'. Those studies analyzing 677C>T polymorphism in male infertility and presenting all relevant data were included in meta-analysis. The genotype data for infertile subjects and fertile controls was extracted from each study. Chi square test was done to obtain odds ratio (OR and p-value. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2. The frequency of mutant (T allele (p = 0.0025 and genotypes (CT+TT (p = 0.0187 was significantly higher in infertile individuals in comparison to fertile controls in our case-control study. The overall summary estimate (OR for allele and genotype meta-analysis were 1.304 (p = 0.000, 1.310 (p = 0.000, respectively, establishing significant association of 677C>T polymorphism with male infertility.677C>T substitution associated strongly with male infertility in Indian population. Allele and genotype meta-analysis also supported its strong correlation with male infertility, thus establishing it as a risk factor.

  6. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

    DEFF Research Database (Denmark)

    Paternoster, Lavinia; Standl, Marie; Chen, Chih-Mei

    2011-01-01

    Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16...

  7. Systematic Review and Meta-Analysis: Is Pre-Injury Antiplatelet Therapy Associated with Traumatic Intracranial Hemorrhage?

    Science.gov (United States)

    van den Brand, Crispijn L; Tolido, Tanya; Rambach, Anna H; Hunink, Myriam G M; Patka, Peter; Jellema, Korné

    2017-01-01

    The objective of this systematic review and meta-analysis is to evaluate whether the pre-injury use of antiplatelet therapy (APT) is associated with increased risk of traumatic intracranial hemorrhage (tICH) on CT scan. PubMed, Medline, Embase, Cochrane Central, reference lists, and national guidelines on traumatic brain injury were used as data sources. Eligible studies were cohort studies and case-control studies that assessed the relationship between APT and tICH. Studies without control group were not included. The primary outcome of interest was tICH on CT. Two reviewers independently selected studies, assessed methodological quality, and extracted outcome data. This search resulted in 10 eligible studies with 20,247 patients with head injury that were included in the meta-analysis. The use of APT in patients with head injury was associated with significant increased risk of tICH compared with control (odds ratio [OR] 1.87, 95% confidence interval [CI]1.27-2.74). There was significant heterogeneity in the studies (I 2 84%), although almost all showed an association between APT use and tICH. This association could not be established for patients receiving aspirin monotherapy. When considering only patients with mild traumatic brain injury (mTBI), the OR is 2.72 (95% CI 1.92-3.85). The results were robust to sensitivity analysis on study quality. In summary, APT in patients with head injury is associated with increased risk of tICH; this association is most relevant in patients with mTBI. Whether this association is the result of a causal relationship and whether this relationship also exists for patients receiving aspirin monotherapy cannot be established with the current review and meta-analysis.

  8. Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study

    DEFF Research Database (Denmark)

    Dijkstra, Akkelies E; Smolonska, Joanna; van den Berge, Maarten

    2014-01-01

    by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism...... (SNP). RESULTS: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression...... of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. METHODS: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed...

  9. COMT Val158Met genotype is associated with reward learning: A replication study and meta-analysis

    Science.gov (United States)

    Corral-Frías, Nadia S.; Pizzagalli, Diego A.; Carré, Justin; Michalski, Lindsay J; Nikolova, Yuliya S.; Perlis, Roy H.; Fagerness, Jesen; Lee, Mary R.; Conley, Emily Drabant; Lancaster, Thomas M.; Haddad, Stephen; Wolf, Aaron; Smoller, Jordan W.; Hariri, Ahmad R.; Bogdan, Ryan

    2016-01-01

    Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val158Met) has been linked to reward learning where homozygosity for the Met allele (associated with heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across 3 separate samples that were combined for analyses (age: 21.80 ± 3.95; n=392; 268 female; European-American, n=208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European-American participants (β=0.20, t= 2.75, p< 0.01; ΔR2= 0.04). Moreover, a meta-analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI −0.11 to −0.03; z=3.2; p<0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction. PMID:27138112

  10. An Empirical Study on User-oriented Association Analysis of Library Classification Schemes

    Directory of Open Access Journals (Sweden)

    Hsiao-Tieh Pu

    2002-12-01

    Full Text Available Library classification schemes are mostly organized based on disciplines with a hierarchical structure. From the user point of view, some highly related yet non-hierarchical classes may not be easy to perceive in these schemes. This paper is to discover hidden associations between classes by analyzing users’ usage of library collections. The proposed approach employs collaborative filtering techniques to discover associated classes based on the circulation patterns of similar users. Many associated classes scattered across different subject hierarchies could be discovered from the circulation patterns of similar users. The obtained association norms between classes were found to be useful in understanding users' subject preferences for a given class. Classification schemes can, therefore, be made more adaptable to changes of users and the uses of different library collections. There are implications for applications in information organization and retrieval as well. For example, catalogers could refer to the ranked associated classes when they perform multi-classification, and users could also browse the associated classes for related subjects in an enhanced OPAC system. In future research, more empirical studies will be needed to validate the findings, and methods for obtaining user-oriented associations can still be improved.[Article content in Chinese

  11. Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

    OpenAIRE

    Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

    2014-01-01

    Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence interval...

  12. Integrating genome-wide association study and expression quantitative trait loci data identifies multiple genes and gene set associated with neuroticism.

    Science.gov (United States)

    Fan, Qianrui; Wang, Wenyu; Hao, Jingcan; He, Awen; Wen, Yan; Guo, Xiong; Wu, Cuiyan; Ning, Yujie; Wang, Xi; Wang, Sen; Zhang, Feng

    2017-08-01

    Neuroticism is a fundamental personality trait with significant genetic determinant. To identify novel susceptibility genes for neuroticism, we conducted an integrative analysis of genomic and transcriptomic data of genome wide association study (GWAS) and expression quantitative trait locus (eQTL) study. GWAS summary data was driven from published studies of neuroticism, totally involving 170,906 subjects. eQTL dataset containing 927,753 eQTLs were obtained from an eQTL meta-analysis of 5311 samples. Integrative analysis of GWAS and eQTL data was conducted by summary data-based Mendelian randomization (SMR) analysis software. To identify neuroticism associated gene sets, the SMR analysis results were further subjected to gene set enrichment analysis (GSEA). The gene set annotation dataset (containing 13,311 annotated gene sets) of GSEA Molecular Signatures Database was used. SMR single gene analysis identified 6 significant genes for neuroticism, including MSRA (p value=2.27×10 -10 ), MGC57346 (p value=6.92×10 -7 ), BLK (p value=1.01×10 -6 ), XKR6 (p value=1.11×10 -6 ), C17ORF69 (p value=1.12×10 -6 ) and KIAA1267 (p value=4.00×10 -6 ). Gene set enrichment analysis observed significant association for Chr8p23 gene set (false discovery rate=0.033). Our results provide novel clues for the genetic mechanism studies of neuroticism. Copyright © 2017. Published by Elsevier Inc.

  13. Association Between rs1344706 of ZNF804A and Schizophrenia: A Meta-analysis

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    Meiyan Zhu

    2014-12-01

    Full Text Available Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism (SNP rs1344706 in the gene ZNF804A encoding zinc finger protein 804A was associated with schizophrenia in Caucasian population but not in Chinese Han population. However, current results are conflicting in Asian population. In the present study, a meta-analysis was performed to revisit the association between rs1344706 and the risk of schizophrenia in Asian, Caucasian and other populations. Electronic search of PubMed database identified 25 case–control studies with available genotype frequencies of rs1344706 for the meta-analysis, involving a total of 15,788 cases and 22,654 controls. A pooled odds ratio (OR with 95% confidence interval (CI was used to assess the association. The current meta-analysis showed an association between rs1344706 and schizophrenia in Caucasian populations (P = 0.028, OR = 1.138, 95% CI: 1.014–1.278; P = 0.004 for heterogeneity and Asian populations (P = 0.008, OR = 1.092, 95% CI: 1.023–1.165; P = 0.001 for heterogeneity, but not in other populations (P = 0.286, OR = 1.209, 95% CI: 0.853–1.714, P = 0.120 for heterogeneity. Egger’s test (P > 0.05 and Begg’s test (P > 0.05 are both suggestive of the lack of publication bias for the included studies. Thus, the absence of association in other populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates the difficulties in replicating genome-wide association study findings regarding schizophrenia across different ethnic populations. To validate the association between rs1344706 and schizophrenia, further studies with larger participant populations worldwide are needed.

  14. Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

    NARCIS (Netherlands)

    Verhoeven, Virginie J. M.; Hysi, Pirro G.; Saw, Seang-Mei; Vitart, Veronique; Mirshahi, Alireza; Guggenheim, Jeremy A.; Cotch, Mary Frances; Yamashiro, Kenji; Baird, Paul N.; Mackey, David A.; Wojciechowski, Robert; Ikram, M. Kamran; Hewitt, Alex W.; Duggal, Priya; Janmahasatian, Sarayut; Khor, Chiea-Chuen; Fan, Qiao; Zhou, Xin; Young, Terri L.; Tai, E.-Shyong; Goh, Liang-Kee; Li, Yi-Ju; Aung, Tin; Vithana, Eranga; teo, Yik-Ying; Tay, Wanting; Sim, Xueling; Rudan, Igor; Hayward, Caroline; Wright, Alan F.; Polasek, Ozren; Campbell, Harry; Wilson, James F.; Fleck, Brian W.; Nakata, Isao; Yoshimura, Nagahisa; Yamada, Ryo; Matsuda, Fumihiko; Ohno-Matsui, Kyoko; Nag, Abhishek; McMahon, George; St Pourcain, Beate; Lu, Yi; Rahi, Jugnoo S.; Cumberland, Phillippa M.; Bhattacharya, Shomi; Simpson, Claire L.; Atwood, Larry D.; Li, Xiaohui; Raffel, Leslie J.; Murgia, Federico; Portas, Laura; Despriet, Dominiek D. G.; van Koolwijk, Leonieke M. E.; Wolfram, Christian; Lackner, Karl J.; Tönjes, Anke; Mägi, Reedik; Lehtimäki, Terho; Kähönen, Mika; Esko, Tõnu; Metspalu, Andres; Rantanen, Taina; Pärssinen, Olavi; Klein, Barbara E.; Meitinger, Thomas; Spector, Timothy D.; Oostra, Ben A.; Smith, Albert V.; de Jong, Paulus T. V. M.; Hofman, Albert; Amin, Najaf; Karssen, Lennart C.; Rivadeneira, Fernando; Vingerling, Johannes R.; Eiríksdóttir, Guðný; Gudnason, Vilmundur; Döring, Angela; Bettecken, Thomas; Uitterlinden, André G.; Williams, Cathy; Zeller, Tanja; Castagné, Raphaële; Oexle, Konrad; van Duijn, Cornelia M.; Iyengar, Sudha K.; Mitchell, Paul; Wang, Jie Jin; Höhn, René; Pfeiffer, Norbert; Bailey-Wilson, Joan E.; Stambolian, Dwight; Wong, Tien-Yin; Hammond, Christopher J.; Klaver, Caroline C. W.

    2012-01-01

    Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis

  15. A comprehensive association analysis of homocysteine metabolic pathway genes in Singaporean Chinese with ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Hui-Qi Low

    Full Text Available BACKGROUND: The effect of genetic factors, apart from 5,10-methylenetetrahydrofolate reductase (MTHFR polymorphisms, on elevated plasma homocysteine levels and increasing ischemic stroke risk have not been fully elucidated. We conducted a comprehensive analysis of 25 genes involved in homocysteine metabolism to investigate association of common variants within these genes with ischemic stroke risk. METHODOLOGY/PRINCIPAL FINDINGS: The study was done in two stages. In the initial study, SNP and haplotype-based association analyses were performed using 147 tagging Single Nucleotide Polymorphisms (SNPs in 360 stroke patients and 354 non-stroke controls of Singaporean Chinese ethnicity. Joint association analysis of significant SNPs was then performed to assess the cumulative effect of these variants on ischemic stroke risk. In the replication study, 8 SNPs were selected for validation in an independent set of 420 matched case-control pairs of Singaporean Chinese ethnicity. SNP analysis from the initial study suggested 3 risk variants in the MTRR, SHMT1 and TCN2 genes which were moderately associated with ischemic stroke risk, independent of known stroke risk factors. Although the replication study failed to support single-SNP associations observed in the initial study, joint association analysis of the 3 variants in combined initial and replication samples revealed a trend of elevated risk with an increased number of risk alleles (Joint P(trend = 1.2×10(-6. CONCLUSIONS: Our study did not find direct evidence of associations between any single polymorphisms of homocysteine metabolic pathway genes and ischemic stroke, but suggests that the cumulative effect of several small to moderate risk variants from genes involved in homocysteine metabolism may jointly confer a significant impact on ischemic stroke risk.

  16. SNP association study in PMS2-associated Lynch syndrome.

    Science.gov (United States)

    Ten Broeke, Sanne W; Elsayed, Fadwa A; Pagan, Lisa; Olderode-Berends, Maran J W; Garcia, Encarna Gomez; Gille, Hans J P; van Hest, Liselot P; Letteboer, Tom G W; van der Kolk, Lizet E; Mensenkamp, Arjen R; van Os, Theo A; Spruijt, Liesbeth; Redeker, Bert J W; Suerink, Manon; Vos, Yvonne J; Wagner, Anja; Wijnen, Juul T; Steyerberg, E W; Tops, Carli M J; van Wezel, Tom; Nielsen, Maartje

    2017-11-17

    Lynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly on MLH1, MSH2 and MSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs in PMS2 mutation carriers. A cohort study was performed in 507 PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. Discrimination was assessed with a concordance statistic in a bootstrap cross-validation procedure. Individual SNPs only had non-significant associations with CRC occurrence with HRs lower than 2, although male carriers of allele A at rs1321311 (6p21.31) may have increased risk of CRC (HR = 2.1, 95% CI 1.2-3.0). A polygenic risk score (PRS) based on 24 HRs had an HR of 2.6 (95% CI 1.5-4.6) for the highest compared to the lowest quartile, but had no discriminative ability (c statistic 0.52). Previously suggested SNPs do not modify CRC risk in PMS2 carriers. Future large studies are needed for improved risk stratification among Lynch syndrome patients.

  17. The Prothrombin G20210A Mutation is Associated with Young-Onset Stroke: The Genetics of Early Onset Stroke Study and Meta-Analysis

    Science.gov (United States)

    Jiang, Baijia; Ryan, Kathleen A.; Hamedani, Ali; Cheng, Yuching; Sparks, Mary J.; Koontz, Deborah; Bean, Christopher J.; Gallagher, Margaret; Hooper, W. Craig; McArdle, Patrick F.; O'Connell, Jeffrey R.; Stine, O. Colin; Wozniak, Marcella A.; Stern, Barney J.; Mitchell, Braxton D.; Kittner, Steven J.; Cole, John W.

    2014-01-01

    Background and Purpose Although the prothrombin G20210A mutation has been implicated as a risk factor for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young-adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in a Caucasian case-control population and additionally performed a meta-analysis Methods From the population-based Genetics of Early Onset Stroke (GEOS) study we identified 397 individuals of European ancestry aged 15-49 years with first-ever ischemic stroke and 426 matched-controls. Logistic regression was used to calculate odds ratios in the entire population and for subgroups stratified by gender, age, oral contraceptive use, migraine and smoking status. A meta-analysis of 17 case-control studies (n=2305 cases ischemic stroke did not achieve statistical significance (OR=2.5,95%CI=0.9-6.5,p=0.07). However, among adults aged 15-42 (younger than median age), cases were significantly more likely than controls to have the mutation (OR=5.9,95%CI=1.2-28.1,p=0.03), whereas adults ages 42-49 were not (OR=1.4,95%CI=0.4-5.1,p=0.94). In our meta-analysis, the mutation was associated with significantly increased stroke risk in adults ischemic stroke in young-adults and may have an even stronger association among those with earlier onset strokes. Our finding of a stronger association in the younger-young adult population requires replication. PMID:24619398

  18. Association between psychosocial stress and hypertension: a systematic review and meta-analysis.

    Science.gov (United States)

    Liu, Mei-Yan; Li, Na; Li, William A; Khan, Hajra

    2017-06-01

    The etiology of hypertension is various and complex, involving both genetic and behavioral factors. The relationship between psychosocial stress and hypertension has been hypothesized. More and more people experience increased anxiety, depression, and chronic psychosocial stress brought on by globalization, cultural changes, socioeconomic changes, and stress at the work place. Although a plethora of studies have investigated the interaction between psychosocial stress and hypertension, this relationship is still contentious. The objective of this study is twofold. First, a review of recent advancements in our understanding of the relationship between psychosocial stress and hypertension. Second, a meta-analysis aiming to assess the relationship between chronic psychosocial stress and blood pressure. We systematically searched and identified relevant studies from five databases, including PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), CQVIP, and the Wanfang Database until April 2016. Eleven studies encompassing 5696 participants were included in the final analysis. Data showed that psychosocial stress was associated with an increased risk of hypertension (OR = 2.40, 95% CI = 1.65-3.49), and hypertensive patients had a higher incidence of psychosocial stress compared to normotension patients (OR = 2.69, 95% CI = 2.32-3.11). Based on our meta-analysis, chronic psychosocial stress may be a risk factor for hypertension. The few cohort and case-control studies on the association between psychosocial stress and hypertension employed variable definition of stressors and the responses, making the meta-analysis difficult. Although we found an association between chronic psychosocial stress and hypertension, more studies are needed to confirm this relationship.

  19. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; van Duijn, Cornelia M; Ugocsai, Peter

    2012-01-01

    , and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57...

  20. Bayesian graphical models for genomewide association studies.

    Science.gov (United States)

    Verzilli, Claudio J; Stallard, Nigel; Whittaker, John C

    2006-07-01

    As the extent of human genetic variation becomes more fully characterized, the research community is faced with the challenging task of using this information to dissect the heritable components of complex traits. Genomewide association studies offer great promise in this respect, but their analysis poses formidable difficulties. In this article, we describe a computationally efficient approach to mining genotype-phenotype associations that scales to the size of the data sets currently being collected in such studies. We use discrete graphical models as a data-mining tool, searching for single- or multilocus patterns of association around a causative site. The approach is fully Bayesian, allowing us to incorporate prior knowledge on the spatial dependencies around each marker due to linkage disequilibrium, which reduces considerably the number of possible graphical structures. A Markov chain-Monte Carlo scheme is developed that yields samples from the posterior distribution of graphs conditional on the data from which probabilistic statements about the strength of any genotype-phenotype association can be made. Using data simulated under scenarios that vary in marker density, genotype relative risk of a causative allele, and mode of inheritance, we show that the proposed approach has better localization properties and leads to lower false-positive rates than do single-locus analyses. Finally, we present an application of our method to a quasi-synthetic data set in which data from the CYP2D6 region are embedded within simulated data on 100K single-nucleotide polymorphisms. Analysis is quick (<5 min), and we are able to localize the causative site to a very short interval.

  1. Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

    Science.gov (United States)

    Demirkan, A; Lahti, J; Direk, N; Viktorin, A; Lunetta, K L; Terracciano, A; Nalls, M A; Tanaka, T; Hek, K; Fornage, M; Wellmann, J; Cornelis, M C; Ollila, H M; Yu, L; Smith, J A; Pilling, L C; Isaacs, A; Palotie, A; Zhuang, W V; Zonderman, A; Faul, J D; Sutin, A; Meirelles, O; Mulas, A; Hofman, A; Uitterlinden, A; Rivadeneira, F; Perola, M; Zhao, W; Salomaa, V; Yaffe, K; Luik, A I; Liu, Y; Ding, J; Lichtenstein, P; Landén, M; Widen, E; Weir, D R; Llewellyn, D J; Murray, A; Kardia, S L R; Eriksson, J G; Koenen, K; Magnusson, P K E; Ferrucci, L; Mosley, T H; Cucca, F; Oostra, B A; Bennett, D A; Paunio, T; Berger, K; Harris, T B; Pedersen, N L; Murabito, J M; Tiemeier, H; van Duijn, C M; Räikkönen, K

    2016-06-01

    Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

  2. Association between periodontal disease and mortality in people with CKD: a meta-analysis of cohort studies.

    Science.gov (United States)

    Zhang, Jian; Jiang, Hong; Sun, Min; Chen, Jianghua

    2017-08-16

    Periodontal disease occurs relatively prevalently in people with chronic kidney disease (CKD), but it remains indeterminate whether periodontal disease is an independent risk factor for premature death in this population. Interventions to reduce mortality in CKD population consistently yield to unsatisfactory results and new targets are necessitated. So this meta-analysis aimed to evaluate the association between periodontal disease and mortality in the CKD population. Pubmed, Embase, Web of Science, Scopus and abstracts from recent relevant meeting were searched by two authors independently. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated for overall and subgroup meta-analyses. Statistical heterogeneity was explored by chi-square test and quantified by the I 2 statistic. Eight cohort studies comprising 5477 individuals with CKD were incorporated. The overall pooled data demonstrated that periodontal disease was associated with all-cause death in CKD population (RR, 1.254; 95% CI 1.046-1.503; P = 0.005), with a moderate heterogeneity, I 2  = 52.2%. However, no evident association was observed between periodontal disease and cardiovascular mortality (RR, 1.30, 95% CI, 0.82-2.06; P = 0.259). Besides, statistical heterogeneity was substantial (I 2  = 72.5%; P = 0.012). Associations for mortality were similar between subgroups, such as the different stages of CKD, adjustment for confounding factors. Specific to all-cause death, sensitivity and cumulative analyses both suggested that our results were robust. As for cardiovascular mortality, the association with periodontal disease needs to be further strengthened. We demonstrated that periodontal disease was associated with an increased risk of all-cause death in CKD people. Yet no adequate evidence suggested periodontal disease was also at elevated risk for cardiovascular death.

  3. Genome-wide association of lipid-lowering response to statins in combined study populations.

    Directory of Open Access Journals (Sweden)

    Mathew J Barber

    2010-03-01

    Full Text Available Statins effectively lower total and plasma LDL-cholesterol, but the magnitude of decrease varies among individuals. To identify single nucleotide polymorphisms (SNPs contributing to this variation, we performed a combined analysis of genome-wide association (GWA results from three trials of statin efficacy.Bayesian and standard frequentist association analyses were performed on untreated and statin-mediated changes in LDL-cholesterol, total cholesterol, HDL-cholesterol, and triglyceride on a total of 3932 subjects using data from three studies: Cholesterol and Pharmacogenetics (40 mg/day simvastatin, 6 weeks, Pravastatin/Inflammation CRP Evaluation (40 mg/day pravastatin, 24 weeks, and Treating to New Targets (10 mg/day atorvastatin, 8 weeks. Genotype imputation was used to maximize genomic coverage and to combine information across studies. Phenotypes were normalized within each study to account for systematic differences among studies, and fixed-effects combined analysis of the combined sample were performed to detect consistent effects across studies. Two SNP associations were assessed as having posterior probability greater than 50%, indicating that they were more likely than not to be genuinely associated with statin-mediated lipid response. SNP rs8014194, located within the CLMN gene on chromosome 14, was strongly associated with statin-mediated change in total cholesterol with an 84% probability by Bayesian analysis, and a p-value exceeding conventional levels of genome-wide significance by frequentist analysis (P = 1.8 x 10(-8. This SNP was less significantly associated with change in LDL-cholesterol (posterior probability = 0.16, P = 4.0 x 10(-6. Bayesian analysis also assigned a 51% probability that rs4420638, located in APOC1 and near APOE, was associated with change in LDL-cholesterol.Using combined GWA analysis from three clinical trials involving nearly 4,000 individuals treated with simvastatin, pravastatin, or atorvastatin, we

  4. Association between TYK2 polymorphisms and susceptibility to autoimmune rheumatic diseases: a meta-analysis.

    Science.gov (United States)

    Lee, Y H; Bae, S-C

    2016-10-01

    This study aimed to explore whether TYK2 polymorphisms are associated with susceptibility to autoimmune rheumatic diseases. We conducted a meta-analysis on the association between TYK2 polymorphisms and autoimmune rheumatic diseases. Twelve studies with a total of 16,335 patients and 30,065 controls were included in the meta-analysis. Meta-analysis revealed an association between rheumatic diseases and the 2 allele of the TYK2 rs2304256 (OR = 0.885, 95% CI = 0.802-0.978, p = 0.016). Furthermore, stratification by ethnicity identified a significant association between this polymorphism and rheumatic diseases in Caucasians (OR = 0.822, 95% CI = 0.706-0.889, p = 9.5 × 10(-7)), but not in Asians (OR = 1.127, 95% CI = 0.835-1.522, p = 0.434). Meta-analysis by rheumatic disease type revealed a significant association between the 2 allele of the TYK2 rs2304256 and SLE in Caucasians (OR = 0.737, 95% CI = 0.673-0.808, p rheumatic diseases in Caucasians (OR = 0.812, 95% CI = 0.661-0.997, p = 0.046) but not in Asians. Interestingly, the rs280519 polymorphism was significantly associated with susceptibility to SLE both in Caucasians and Asians. However, no associations were found between the rs12720270, rs280500, rs280523 and rs8108236 polymorphisms and susceptibility to rheumatic diseases. This meta-analysis demonstrates that the TYK2 rs2304256 and rs12720356 polymorphisms are associated with susceptibility to rheumatic diseases, rs2304256 polymorphism is associated with SLE in Caucasians, and rs280519 polymorphism is associated with SLE in Caucasians and Asians. © The Author(s) 2016.

  5. Lack of association between cytotoxic T-lymphocyte antigen 4 (CTLA-4 -1722T/C (rs733618 polymorphism and cancer risk: from a case-control study to a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Weifeng Tang

    Full Text Available BACKGROUND: The association between cytotoxic T-lymphocyte antigen 4 (CTLA-4 gene -1722T/C polymorphism (rs733618 and cancer has been widely assessed, and a definitive conclusion remains elusive. We first performed a hospital based case-control study to measure this association of esophageal cancer with CTLA-4 -1722T/C polymorphism in Han Chinese population, and then carried out a meta-analysis to obtain a comprehensive evaluation for this issue. METHODOLOGY/PRINCIPAL FINDINGS: This case-control study involved 629 esophageal squamous cell carcinoma (ESCC cases and 686 age and gender well matched cancer-free controls. PCR-LDR (polymerase chain reaction-ligase detection reactions method was used to identify genotypes. Meta-analysis was conducted by STATA (v12.0 software. This case-control study showed no significant difference in the genotype and allele distributions of CTLA-4 -1722T/C polymorphism between esophageal cancer cases and control subjects, in accord with the findings of the further meta-analysis in all genetic models. Evidence of large heterogeneity was observed among all eligible studies in the recessive model. Further subgroup analyses by ethnicity, cancer type and system, detected null associations in this meta-analysis. CONCLUSION: This case-control study and the further meta-analysis, failed to identify the association between CTLA-4 -1722T/C polymorphism and cancer risk.

  6. Sequential sentinel SNP Regional Association Plots (SSS-RAP): an approach for testing independence of SNP association signals using meta-analysis data.

    Science.gov (United States)

    Zheng, Jie; Gaunt, Tom R; Day, Ian N M

    2013-01-01

    Genome-Wide Association Studies (GWAS) frequently incorporate meta-analysis within their framework. However, conditional analysis of individual-level data, which is an established approach for fine mapping of causal sites, is often precluded where only group-level summary data are available for analysis. Here, we present a numerical and graphical approach, "sequential sentinel SNP regional association plot" (SSS-RAP), which estimates regression coefficients (beta) with their standard errors using the meta-analysis summary results directly. Under an additive model, typical for genes with small effect, the effect for a sentinel SNP can be transformed to the predicted effect for a possibly dependent SNP through a 2×2 2-SNP haplotypes table. The approach assumes Hardy-Weinberg equilibrium for test SNPs. SSS-RAP is available as a Web-tool (http://apps.biocompute.org.uk/sssrap/sssrap.cgi). To develop and illustrate SSS-RAP we analyzed lipid and ECG traits data from the British Women's Heart and Health Study (BWHHS), evaluated a meta-analysis for ECG trait and presented several simulations. We compared results with existing approaches such as model selection methods and conditional analysis. Generally findings were consistent. SSS-RAP represents a tool for testing independence of SNP association signals using meta-analysis data, and is also a convenient approach based on biological principles for fine mapping in group level summary data. © 2012 Blackwell Publishing Ltd/University College London.

  7. Associations between sensory loss and social networks, participation, support, and loneliness: Analysis of the Canadian Longitudinal Study on Aging.

    Science.gov (United States)

    Mick, Paul; Parfyonov, Maksim; Wittich, Walter; Phillips, Natalie; Kathleen Pichora-Fuller, M

    2018-01-01

    To determine if hearing loss, vision loss, and dual sensory loss were associated with social network diversity, social participation, availability of social support, and loneliness, respectively, in a population-based sample of older Canadians and to determine whether age or sex modified the associations. Cross-sectional population-based study. Canada. The sample included 21 241 participants in the Canadian Longitudinal Study on Aging tracking cohort. The sample was nationally representative of English- and French-speaking, non-institutionalized 45- to 89-year-old Canadians who did not live on First Nations reserves and who had normal cognition. Participants with missing data for any of the variables in the multivariable regression models were excluded from analysis. Hearing and vision loss were determined by self-report. Dual sensory loss was defined as reporting both hearing and vision loss. Univariate analyses were performed to assess cross-sectional associations between hearing, vision, and dual sensory loss, and social, demographic, and medical variables. Multivariable regression models were used to analyze cross-sectional associations between each type of sensory loss and social network diversity, social participation, availability of social support, and loneliness. Vision loss (in men) and dual sensory loss (in 65- to 85-year-olds) were independently associated with reduced social network diversity. Vision loss and dual sensory loss (in 65- to 85-year-olds) were each independently associated with reduced social participation. All forms of sensory loss were associated with both low availability of social support and loneliness. Sensory impairment is associated with reduced social function in older Canadians. Interventions and research that address the social needs of older individuals with sensory loss are needed. Copyright© the College of Family Physicians of Canada.

  8. Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yu-Tao Qin

    Full Text Available Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR polymorphisms and acute myeloid leukemia risk (AML have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs with 95% confidence intervals (CIs were the metric of choice. Thirteen studies were selected for C677T polymorphism (1838 cases and 5318 controls and 9 studies (1335 patients and 4295 controls for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism was not significant associated with AML risk(OR, 0.98-1.04; 95% CI, 0.86-0.92 to 1.09-1.25. Similar results were observed for the A1298C polymorphism and in subgroup analysis. All comparisons revealed no substantial heterogeneity nor did we detect evidence of publication bias. In summary, this meta-analysis provides evidence that MTHFR polymorphisms were not associated with AML risk. Further investigations are needed to offer better insight into the role of these polymorphisms in AML carcinogenesis.

  9. Association of matrix metalloproteinase-3 -1171(5A>6A polymorphism with cancer risk: a meta-analysis of 41 studies.

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    Xin Yang

    Full Text Available BACKGROUND AND OBJECTIVE: Evidence has shown that matrix metalloproteinases-3 (MMP3 is important for cancer progression. Recent studies about the association between the -1171(5A>6A polymorphism in MMP3 promoter region and cancer risk have yielded conflicting results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 41 studies including 11112 cases and 11091 controls to determine whether the -1171(5A>6A polymorphism of MMP3 was associated with cancer risk. We assessed the strength of association and performed sub-group analyses by cancer types, ethnicity, smoking status, genotyping method, source of controls and sample size. The pooled results revealed that no significant association of the -1171(5A>6A polymorphism with overall cancer risk in any of four models. Further sub-group analysis revealed that individuals with the 6A allele had lower risk of gastrointestinal cancer in two models: heterozygote comparison (6A/5A vs. 5A/5A: OR=0.74, 95%CI: 0.60-0.91; I(2=1.9%, and dominant model (6A/6A+6A/5A vs. 5A/5A: OR=0.77, 95%CI: 0.64-0.94; I(2=29.0%. Additionally, the associations were significant in Asian populations for three models: homozygote comparison (6A/6A vs. 5A/5A, OR=0.68, 95%CI: 0.52-0.90; I(2=26.7%, heterozygote comparison (6A/5A vs. 5A/5A: OR=0.75, 95%CI: 0.58-0.98; I(2=0.0%, and dominant model (6A/6A+6A/5A vs. 5A/5A: OR=0.69, 95%CI: 0.54-0.88; I(2=0.5%. It was noteworthy that we had a contrary finding in non-smokers: the variant 6A/6A homozygote might statistically increase cancer risk compared with 6A/5A+5A/5A genotype (OR=1.92, 95%CI: 1.25-2.96; I(2=72.7%. CONCLUSION: This meta-analysis suggests that the -1171(5A>6A polymorphism in MMP3 promoter region is not associated with overall cancer risk, but it may contribute to decreased cancer risk in Asian population when compared with Caucasian population and significantly reduce the risk of gastrointestinal cancer.

  10. The association between maternal smoking and placenta abruption: a meta-analysis.

    Science.gov (United States)

    Shobeiri, Fatemeh; Masoumi, Seyedeh Zahra; Jenabi, Ensiyeh

    2017-08-01

    Several epidemiological studies have determined that maternal smoking can increase the risk of placenta abruption. To date, only a meta-analysis has been performed for assessing the relationship between smoking and placenta abruption. This meta-analysis was conducted to estimate the association between smoking and the risk of placenta abruption. A literature search was conducted in major databases such as PubMed, Web of Science, and Scopus from the earliest possible year to April 2016. The heterogeneity across studies was explored by Q-test and I 2 statistic. The publication bias was assessed using Begg's and Egger's tests. The results were reported using odds ratio (OR) estimate with its 95% confidence intervals (CI) using a random effects model. The literature search yielded 1167 publications until April 2016 with 4 309 610 participants. Based on OR estimates obtained from case-control and cohort studies, there was a significant association between smoking and placenta abruption (1.80; 95% CI: 1.75, 1.85). Based on the results of cohort studies, smoking and placenta abruption had a significant association (relative risk ratio: 1.65; 95% CI: 1.51, 1.80). Based on reports in epidemiological studies, we showed that smoking is a risk factor for placenta abruption.

  11. Association Between Blood Glucose and Functional Outcome in Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Zheng, Jun; Yu, Zhiyuan; Ma, Lu; Guo, Rui; Lin, Sen; You, Chao; Li, Hao

    2018-03-16

    Intracerebral hemorrhage (ICH) is a devastating subtype of stroke. Patients with ICH have poor functional outcomes. The association between blood glucose level and functional outcome in ICH remains unclear. This systematic review and meta-analysis aimed to investigate the association between blood glucose level and functional outcomes in patients with ICH. Literature was searched systemically in PubMed, EMBASE, Web of Science, and Cochrane Library. Published cohort studies evaluating the association between blood glucose and functional outcome in patients with ICH were included. This meta-analysis was performed using odds ratios (ORs) and 95% confidence intervals (CIs). A total of 16 studies were included in our meta-analysis. Our data show that hyperglycemia defined by cutoff values was significantly associated with unfavorable functional outcome (OR, 1.80; 95% CI, 1.36-2.39; P analysis also suggested a significant association between increased blood glucose levels and functional outcomes (OR, 1.05; 95% CI, 1.03-1.07; P functional outcome in ICH. Further studies with larger sample sizes, more time points, and longer follow-up times are necessary to confirm this association. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Meta-analysis of the INSIG2 association with obesity including 74,345 individuals: does heterogeneity of estimates relate to study design?

    DEFF Research Database (Denmark)

    Heid, Iris M; Huth, Cornelia; Loos, Ruth J F

    2009-01-01

    with subjects selected for conditions related to a better health status ('healthy population', HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did......The INSIG2 rs7566605 polymorphism was identified for obesity (BMI> or =30 kg/m(2)) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies...... not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I(2) measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I(2) measure of 11% (p-value = 0.33) and an OR of 1.10 (p...

  13. Association between Helicobacter pylori Infection and Chronic Urticaria: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Huiyuan Gu

    2015-01-01

    Full Text Available Background. Some studies have shown the possible involvement of Helicobacter pylori (H. pylori infection in chronic urticaria, but the relationship remains controversial. The aim of this meta-analysis was to quantitatively assess the association between H. pylori infection and chronic urticaria. Methods. Observational studies comparing the prevalence of H. pylori infection in patients with chronic urticaria and control subjects were identified through a systematic search in MEDLINE and EMBASE up to July 2014. H. pylori infection was confirmed by serological or nonserological tests. For subgroup analyses, studies were separated by region, publication year, and H. pylori detection method to screen the potential factors resulting in heterogeneity. Results. 16 studies involving 965 CU cases and 1235 controls were included. Overall, the prevalence of H. pylori infection was higher in urticarial patients than in controls (OR = 1.66; 95% CI: 1.12–2.45; P=0.01. This result persisted in subanalysis of nine high-quality studies (OR = 1.36; 95% CI: 1.03–1.80; P=0.03. Subgroup analysis showed that detection method of H. pylori is also a potential influential factor for the overall results. Conclusions. Our present meta-analysis suggests that H. pylori infection is significantly, though weakly, associated with an increased risk of chronic urticaria.

  14. Association between coffee intake and gastroesophageal reflux disease: a meta-analysis.

    Science.gov (United States)

    Kim, J; Oh, S-W; Myung, S-K; Kwon, H; Lee, C; Yun, J M; Lee, H K

    2014-01-01

    Gastroesophageal reflux disease (GERD) is one of the most common diseases affecting patients worldwide, but its risk factors and causes are not clearly known. The aim of this study was to investigate the effect of coffee intake on GERD by a meta-analysis. We searched online published research databases such as PubMed, EMBASE, and Cochrane Library for studies that were published up to December 2012. These publications were reviewed by two independent authors, and studies that fulfilled the criteria were selected. Whenever there was a disagreement between the authors, a consensus was reached by discussion. Fifteen case-control studies were included in the final analysis. A meta-analysis showed that there was no significant association between coffee intake and GERD. The odds ratio was 1.06 (95% confidence interval, 0.94-1.19). In subgroup analyses in which the groups were subdivided based on the definition of GERD (diagnosed by endoscopy or by symptoms alone), only the endoscopy group showed a significantly higher odds ratio. In subgroup analyses in which the groups were subdivided based on the amount of coffee intake, quality of study, and assessment of exposure, there was no significant association between coffee intake and GERD. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  15. A genome-wide association study of aging.

    Science.gov (United States)

    Walter, Stefan; Atzmon, Gil; Demerath, Ellen W; Garcia, Melissa E; Kaplan, Robert C; Kumari, Meena; Lunetta, Kathryn L; Milaneschi, Yuri; Tanaka, Toshiko; Tranah, Gregory J; Völker, Uwe; Yu, Lei; Arnold, Alice; Benjamin, Emelia J; Biffar, Reiner; Buchman, Aron S; Boerwinkle, Eric; Couper, David; De Jager, Philip L; Evans, Denis A; Harris, Tamara B; Hoffmann, Wolfgang; Hofman, Albert; Karasik, David; Kiel, Douglas P; Kocher, Thomas; Kuningas, Maris; Launer, Lenore J; Lohman, Kurt K; Lutsey, Pamela L; Mackenbach, Johan; Marciante, Kristin; Psaty, Bruce M; Reiman, Eric M; Rotter, Jerome I; Seshadri, Sudha; Shardell, Michelle D; Smith, Albert V; van Duijn, Cornelia; Walston, Jeremy; Zillikens, M Carola; Bandinelli, Stefania; Baumeister, Sebastian E; Bennett, David A; Ferrucci, Luigi; Gudnason, Vilmundur; Kivimaki, Mika; Liu, Yongmei; Murabito, Joanne M; Newman, Anne B; Tiemeier, Henning; Franceschini, Nora

    2011-11-01

    Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10(-8)). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10(-5)). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

    Science.gov (United States)

    Elks, Cathy E.; Perry, John R.B.; Sulem, Patrick; Chasman, Daniel I.; Franceschini, Nora; He, Chunyan; Lunetta, Kathryn L.; Visser, Jenny A.; Byrne, Enda M.; Cousminer, Diana L.; Gudbjartsson, Daniel F.; Esko, Tõnu; Feenstra, Bjarke; Hottenga, Jouke-Jan; Koller, Daniel L.; Kutalik, Zoltán; Lin, Peng; Mangino, Massimo; Marongiu, Mara; McArdle, Patrick F.; Smith, Albert V.; Stolk, Lisette; van Wingerden, Sophie W.; Zhao, Jing Hua; Albrecht, Eva; Corre, Tanguy; Ingelsson, Erik; Hayward, Caroline; Magnusson, Patrik K.E.; Smith, Erin N.; Ulivi, Shelia; Warrington, Nicole M.; Zgaga, Lina; Alavere, Helen; Amin, Najaf; Aspelund, Thor; Bandinelli, Stefania; Barroso, Ines; Berenson, Gerald S.; Bergmann, Sven; Blackburn, Hannah; Boerwinkle, Eric; Buring, Julie E.; Busonero, Fabio; Campbell, Harry; Chanock, Stephen J.; Chen, Wei; Cornelis, Marilyn C.; Couper, David; Coviello, Andrea D.; d’Adamo, Pio; de Faire, Ulf; de Geus, Eco J.C.; Deloukas, Panos; Döring, Angela; Smith, George Davey; Easton, Douglas F.; Eiriksdottir, Gudny; Emilsson, Valur; Eriksson, Johan; Ferrucci, Luigi; Folsom, Aaron R.; Foroud, Tatiana; Garcia, Melissa; Gasparini, Paolo; Geller, Frank; Gieger, Christian; Gudnason, Vilmundur; Hall, Per; Hankinson, Susan E.; Ferreli, Liana; Heath, Andrew C.; Hernandez, Dena G.; Hofman, Albert; Hu, Frank B.; Illig, Thomas; Järvelin, Marjo-Riitta; Johnson, Andrew D.; Karasik, David; Khaw, Kay-Tee; Kiel, Douglas P.; Kilpeläinen, Tuomas O.; Kolcic, Ivana; Kraft, Peter; Launer, Lenore J.; Laven, Joop S.E.; Li, Shengxu; Liu, Jianjun; Levy, Daniel; Martin, Nicholas G.; McArdle, Wendy L.; Melbye, Mads; Mooser, Vincent; Murray, Jeffrey C.; Murray, Sarah S.; Nalls, Michael A.; Navarro, Pau; Nelis, Mari; Ness, Andrew R.; Northstone, Kate; Oostra, Ben A.; Peacock, Munro; Palmer, Lyle J.; Palotie, Aarno; Paré, Guillaume; Parker, Alex N.; Pedersen, Nancy L.; Peltonen, Leena; Pennell, Craig E.; Pharoah, Paul; Polasek, Ozren; Plump, Andrew S.; Pouta, Anneli; Porcu, Eleonora; Rafnar, Thorunn; Rice, John P.; Ring, Susan M.; Rivadeneira, Fernando; Rudan, Igor; Sala, Cinzia; Salomaa, Veikko; Sanna, Serena; Schlessinger, David; Schork, Nicholas J.; Scuteri, Angelo; Segrè, Ayellet V.; Shuldiner, Alan R.; Soranzo, Nicole; Sovio, Ulla; Srinivasan, Sathanur R.; Strachan, David P.; Tammesoo, Mar-Liis; Tikkanen, Emmi; Toniolo, Daniela; Tsui, Kim; Tryggvadottir, Laufey; Tyrer, Jonathon; Uda, Manuela; van Dam, Rob M.; van Meurs, Joyve B.J.; Vollenweider, Peter; Waeber, Gerard; Wareham, Nicholas J.; Waterworth, Dawn M.; Weedon, Michael N.; Wichmann, H. Erich; Willemsen, Gonneke; Wilson, James F.; Wright, Alan F.; Young, Lauren; Zhai, Guangju; Zhuang, Wei Vivian; Bierut, Laura J.; Boomsma, Dorret I.; Boyd, Heather A.; Crisponi, Laura; Demerath, Ellen W.; van Duijn, Cornelia M.; Econs, Michael J.; Harris, Tamara B.; Hunter, David J.; Loos, Ruth J.F.; Metspalu, Andres; Montgomery, Grant W.; Ridker, Paul M.; Spector, Tim D.; Streeten, Elizabeth A.; Stefansson, Kari; Thorsteinsdottir, Unnur; Uitterlinden, André G.; Widen, Elisabeth; Murabito, Joanne M.; Ong, Ken K.; Murray, Anna

    2011-01-01

    To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P=5.4×10−60) and 9q31.2 (P=2.2×10−33), we identified 30 novel menarche loci (all P<5×10−8) and found suggestive evidence for a further 10 loci (P<1.9×10−6). New loci included four previously associated with BMI (in/near FTO, SEC16B, TRA2B and TMEM18), three in/near other genes implicated in energy homeostasis (BSX, CRTC1, and MCHR2), and three in/near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and MAGENTA pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing. PMID:21102462

  17. Comprehensive analysis of preeclampsia-associated DNA methylation in the placenta.

    Directory of Open Access Journals (Sweden)

    Tianjiao Chu

    Full Text Available A small number of recent reports have suggested that altered placental DNA methylation may be associated with early onset preeclampsia. It is important that further studies be undertaken to confirm and develop these findings. We therefore undertook a systematic analysis of DNA methylation patterns in placental tissue from 24 women with preeclampsia and 24 with uncomplicated pregnancy outcome.We analyzed the DNA methylation status of approximately 27,000 CpG sites in placental tissues in a massively parallel fashion using an oligonucleotide microarray. Follow up analysis of DNA methylation at specific CpG loci was performed using the Epityper MassArray approach and high-throughput bisulfite sequencing.Preeclampsia-specific DNA methylation changes were identified in placental tissue samples irrespective of gestational age of delivery. In addition, we identified a group of CpG sites within specific gene sequences that were only altered in early onset-preeclampsia (EOPET although these DNA methylation changes did not correlate with altered mRNA transcription. We found evidence that fetal gender influences DNA methylation at autosomal loci but could find no clear association between DNA methylation and gestational age.Preeclampsia is associated with altered placental DNA methylation. Fetal gender should be carefully considered during the design of future studies in which placental DNA is analyzed at the level of DNA methylation. Further large-scale analyses of preeclampsia-associated DNA methylation are necessary.

  18. Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations.

    Science.gov (United States)

    Gorlova, Olga Y; Li, Yafang; Gorlov, Ivan; Ying, Jun; Chen, Wei V; Assassi, Shervin; Reveille, John D; Arnett, Frank C; Zhou, Xiaodong; Bossini-Castillo, Lara; Lopez-Isac, Elena; Acosta-Herrera, Marialbert; Gregersen, Peter K; Lee, Annette T; Steen, Virginia D; Fessler, Barri J; Khanna, Dinesh; Schiopu, Elena; Silver, Richard M; Molitor, Jerry A; Furst, Daniel E; Kafaja, Suzanne; Simms, Robert W; Lafyatis, Robert A; Carreira, Patricia; Simeon, Carmen Pilar; Castellvi, Ivan; Beltran, Emma; Ortego, Norberto; Amos, Christopher I; Martin, Javier; Mayes, Maureen D

    2018-01-01

    Gene-level analysis of ImmunoChip or genome-wide association studies (GWAS) data has not been previously reported for systemic sclerosis (SSc, scleroderma). The objective of this study was to analyze genetic susceptibility loci in SSc at the gene level and to determine if the detected associations were shared in African-American and White populations, using data from ImmunoChip and GWAS genotyping studies. The White sample included 1833 cases and 3466 controls (956 cases and 2741 controls from the US and 877 cases and 725 controls from Spain) and the African American sample, 291 cases and 260 controls. In both Whites and African Americans, we performed a gene-level analysis that integrates association statistics in a gene possibly harboring multiple SNPs with weak effect on disease risk, using Versatile Gene-based Association Study (VEGAS) software. The SNP-level analysis was performed using PLINK v.1.07. We identified 4 novel candidate genes (STAT1, FCGR2C, NIPSNAP3B, and SCT) significantly associated and 4 genes (SERBP1, PINX1, TMEM175 and EXOC2) suggestively associated with SSc in the gene level analysis in White patients. As an exploratory analysis we compared the results on Whites with those from African Americans. Of previously established susceptibility genes identified in Whites, only TNFAIP3 was significant at the nominal level (p = 6.13x10-3) in African Americans in the gene-level analysis of the ImmunoChip data. Among the top suggestive novel genes identified in Whites based on the ImmunoChip data, FCGR2C and PINX1 were only nominally significant in African Americans (p = 0.016 and p = 0.028, respectively), while among the top novel genes identified in the gene-level analysis in African Americans, UNC5C (p = 5.57x10-4) and CLEC16A (p = 0.0463) were also nominally significant in Whites. We also present the gene-level analysis of SSc clinical and autoantibody phenotypes among Whites. Our findings need to be validated by independent studies, particularly

  19. Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.

    Directory of Open Access Journals (Sweden)

    Conall M O'Seaghdha

    Full Text Available Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤ 21,679 additional individuals. Seven loci (six new regions in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12, rs10491003 upstream of GATA3 (P = 4.8E-09 and rs7481584 in CARS (P = 1.2E-10 implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11, also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10 are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

  20. Risk of road accident associated with the use of drugs: a systematic review and meta-analysis of evidence from epidemiological studies.

    Science.gov (United States)

    Elvik, Rune

    2013-11-01

    This paper is a corrigendum to a previously published paper where errors were detected. The errors have been corrected in this paper. The paper is otherwise identical to the previously published paper. A systematic review and meta-analysis of studies that have assessed the risk of accident associated with the use of drugs when driving is presented. The meta-analysis included 66 studies containing a total of 264 estimates of the effects on accident risk of using illicit or prescribed drugs when driving. Summary estimates of the odds ratio of accident involvement are presented for amphetamines, analgesics, anti-asthmatics, anti-depressives, anti-histamines, benzodiazepines, cannabis, cocaine, opiates, penicillin and zopiclone (a sleeping pill). For most of the drugs, small or moderate increases in accident risk associated with the use of the drugs were found. Information about whether the drugs were actually used while driving and about the doses used was often imprecise. Most studies that have evaluated the presence of a dose-response relationship between the dose of drugs taken and the effects on accident risk confirm the existence of a dose-response relationship. Use of drugs while driving tends to have a larger effect on the risk of fatal and serious injury accidents than on the risk of less serious accidents (usually property-damage-only accidents). The quality of the studies that have assessed risk varied greatly. There was a tendency for the estimated effects of drug use on accident risk to be smaller in well-controlled studies than in poorly controlled studies. Evidence of publication bias was found for some drugs. The associations found cannot be interpreted as causal relationships, principally because most studies do not control very well for potentially confounding factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Association of fructose consumption and components of metabolic syndrome in human studies: a systematic review and meta-analysis.

    Science.gov (United States)

    Kelishadi, Roya; Mansourian, Marjan; Heidari-Beni, Motahar

    2014-05-01

    The aim of this study was to review the current corpus of human studies to determine the association of various doses and durations of fructose consumption on metabolic syndrome. We searched human studies in PubMed, Scopus, Ovid, ISI Web of Science, Cochrane library, and Google Scholar databases. We searched for the following keywords in each paper: metabolic syndrome x, insulin resistance, blood glucose, blood sugar, fasting blood sugar, triglycerides, lipoproteins, HDL, cholesterol, LDL, blood pressure, mean arterial pressure, systolic blood pressure, diastolic blood pressure, hypertens*, waist circumference, and fructose, sucrose, high-fructose corn syrup, or sugar. Overall, 3102 articles were gathered. We excluded studies on natural fructose content of foods, non-clinical trials, and trials in which fructose was recommended exclusively as sucrose or high-fructose corn syrup. Overall, 3069 articles were excluded. After review by independent reviewers, 15 studies were included in the meta-analysis. Fructose consumption was positively associated with increased fasting blood sugar (FBS; summary mean difference, 0.307; 95% confidence interval [CI], 0.149-0.465; P = 0.002), elevated triglycerides (TG; 0.275; 95% CI, 0.014-0.408; P = 0.002); and elevated systolic blood pressure (SBP; 0.297; 95% CI, 0.144-0.451; P = 0.002). The corresponding figure was inverse for high-density lipoprotein (HDL) cholesterol (-0.267; 95% CI, -0.406 to -0.128; P = 0.001). Significant heterogeneity existed between studies, except for FBS. After excluding studies that led to the highest effect on the heterogeneity test, the association between fructose consumption and TG, SBP, and HDL became non-significant. The results did not show any evidence of publication bias. No missing studies were identified with the trim-and-fill method. Fructose consumption from industrialized foods has significant effects on most components of metabolic syndrome. Copyright © 2014 Elsevier Inc. All rights

  2. Quantitative analysis of dynamic association in live biological fluorescent samples.

    Directory of Open Access Journals (Sweden)

    Pekka Ruusuvuori

    Full Text Available Determining vesicle localization and association in live microscopy may be challenging due to non-simultaneous imaging of rapidly moving objects with two excitation channels. Besides errors due to movement of objects, imaging may also introduce shifting between the image channels, and traditional colocalization methods cannot handle such situations. Our approach to quantifying the association between tagged proteins is to use an object-based method where the exact match of object locations is not assumed. Point-pattern matching provides a measure of correspondence between two point-sets under various changes between the sets. Thus, it can be used for robust quantitative analysis of vesicle association between image channels. Results for a large set of synthetic images shows that the novel association method based on point-pattern matching demonstrates robust capability to detect association of closely located vesicles in live cell-microscopy where traditional colocalization methods fail to produce results. In addition, the method outperforms compared Iterated Closest Points registration method. Results for fixed and live experimental data shows the association method to perform comparably to traditional methods in colocalization studies for fixed cells and to perform favorably in association studies for live cells.

  3. The association between the FABP2 Ala54Thr variant and the risk of type 2 diabetes mellitus: a meta-analysis based on 11 case-control studies

    OpenAIRE

    Liu, Peng; Yu, Dan; Jin, Xiaoping; Li, Cai; Zhu, Feng; Zheng, Zhou; Lv, Chenlin; He, Xinwei

    2015-01-01

    Fatty acid binding protein 2 (FABP2) Ala54Thr gene polymorphism has been suggested to be associated with the increased risk of developing type 2 diabetes mellitus (T2DM), but some studies show the inconsistent result. The purpose of this meta-analysis is to assess the association between FABP2 Ala54Thr gene polymorphism variants and the T2DM. A total of 7095 subjects in 11 case-control studies were included in this meta-analysis. Under the allele model (T versus A), the pooled OR of Asian sub...

  4. A meta-analysis of the association between mental disorders and juvenile recidivism

    NARCIS (Netherlands)

    Wibbelink, C.J.M.; Hoeve, M.; Stams, G.J.J.M.; Oort, F.J.

    To investigate the association between mental disorders and recidivism in juveniles, a three-level meta-analysis of 20 manuscripts (17 independent studies, N = 5737 juveniles) was conducted. The study focused on internalizing disorders, externalizing disorders, and comorbid disorders (combinations

  5. Analysis of the socio-economic factors associated with gum Arabic ...

    African Journals Online (AJOL)

    The study is an analysis of the socio-economic factors associated with gum arabic collectors in Northern Guinea Savanna Zone of Adamawa State, Nigeria through a questionnaire survey on a sample of 100 respondents obtained through a multi stage sampling technique. Data collected were analyzed using descriptive ...

  6. Associations of CTLA4 Gene Polymorphisms with Graves’ Ophthalmopathy: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Pengfei Du

    2014-01-01

    Full Text Available Many studies have established that T-lymphocyte antigen-4 (CTLA4 is a susceptible gene for Graves’ disease (GD. Also many studies showed the association between the CTLA4 exon-1 49A/G polymorphism and the risk of developing Graves’ ophthalmopathy (GO in GD patients. But those results were inconsistent. In recent years many new studies were published which helped to shed light on the relationship of CTLA4 SNP49 with GO. So we performed the meta-analysis to explore the association between the SNP49 and GO susceptibility in GD patients. Studies up to February 29, 2012, were searched by using PubMed. The odds ratio was used to evaluate the strength of the association. Altogether 12 case-control studies involving 2,505 participants were included in the meta-analysis. Results showed that the G allele was related to the increased risk of GO compared with the A allele under allelic genetic model (OR = 1.14, 95% CI: 1.14–1.72, P=0.001 in European subgroup. No publication bias was detected. Our results showed that the SNP49 polymorphism of CTLA4 gene was related to increased risk of GO.

  7. Oscillatory neuronal dynamics associated with manual acupuncture: a magnetoencephalography study using beamforming analysis

    Directory of Open Access Journals (Sweden)

    Aziz eAsghar

    2012-11-01

    Full Text Available Magnetoencephalography (MEG enables non-invasive recording of neuronal activity, with reconstruction methods providing estimates of underlying brain source locations and oscillatory dynamics from externally recorded neuromagnetic fields. The aim of our study was to use MEG to determine the effect of manual acupuncture on neuronal oscillatory dynamics. A major problem in MEG investigations of manual acupuncture is the absence of onset times for each needle manipulation. Given that beamforming (spatial filtering analysis is not dependent upon stimulus-driven responses being phase-locked to stimulus onset, we postulated that beamforming could reveal source locations and induced changes in neuronal activity during manual acupuncture. In a beamformer analysis, a two-minute period of manual acupuncture needle manipulation delivered to the ipsilateral right LI-4 (Hegu acupoint was contrasted with a two-minute baseline period. We considered oscillatory power changes in the theta (4-8Hz, alpha (8-13Hz, beta (13-30Hz and gamma (30-100Hz frequency bands. We found significant decreases in beta band power in the contralateral primary somatosensory cortex and superior frontal gyrus. In the ipsilateral cerebral hemisphere, we found significant power decreases in beta and gamma frequency bands in only the superior frontal gyrus. No significant power modulations were found in theta and alpha bands. Our results indicate that beamforming is a useful analytical tool to reconstruct underlying neuronal activity associated with manual acupuncture. Our main finding was of beta power decreases in primary somatosensory cortex and superior frontal gyrus, which opens up a line of future investigation regarding whether this contributes towards an underlying mechanism of acupuncture.

  8. Associations between interleukin-1 gene polymorphisms and coronary heart disease risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Liang Zhou

    Full Text Available OBJECTIVE: A great number of studies regarding the associations between IL-1B-511, IL-1B+3954 and IL-1RN VNTR polymorphisms within the IL-1gene cluster and coronary heart disease (CHD have been published. However, results have been inconsistent. In this study, a meta-analysis was performed to investigate the associations. METHODS: Published literature from PubMed and Embase databases were searched for eligible publications. Pooled odds ratios (ORs with 95% confidence intervals (CIs were calculated using random- or fixed- effect model. RESULTS: Thirteen studies (3,219 cases/2,445 controls for IL-1B-511 polymorphism, nine studies (1,828 cases/1,818 controls for IL-1B+3954 polymorphism and twelve studies (2,987 cases/ 2,208 controls for IL-1RN VNTR polymorphism were included in this meta analysis. The results indicated that both IL-1B-511 and IL-1B+3954 polymorphisms were not associated with CHD risk (IL-1B-511 T vs. C: OR = 0.98, 95%CI 0.87-1.09; IL-1B+3954 T vs. C: OR = 1.06, 95%CI 0.95-1.19. Similarly, there was no association between IL-1RN VNTR polymorphism and CHD risk (*2 vs. L: OR = 1.00, 95%CI 0.85-1.17. CONCLUSIONS: This meta-analysis suggested that there were no associations between IL-1 gene cluster polymorphisms and CHD.

  9. Safety-critical event risk associated with cell phone tasks as measured in naturalistic driving studies: A systematic review and meta-analysis.

    Science.gov (United States)

    Simmons, Sarah M; Hicks, Anne; Caird, Jeff K

    2016-02-01

    A systematic review and meta-analysis of naturalistic driving studies involving estimates of safety-critical event risk associated with handheld device use while driving is described. Fifty-seven studies identified from targeted databases, journals and websites were reviewed in depth, and six were ultimately included. These six studies, published between 2006 and 2014, encompass seven sets of naturalistic driver data and describe original research that utilized naturalistic methods to assess the effects of distracting behaviors. Four studies involved non-commercial drivers of light vehicles and two studies involved commercial drivers of trucks and buses. Odds ratios quantifying safety-critical event (SCE) risk associated with talking, dialing, locating or answering, and texting or browsing were extracted. Stratified meta-analysis of pooled odds ratios was used to estimate SCE risk by distraction type; meta-regression was used to test for sources of heterogeneity. The results indicate that tasks that require drivers to take their eyes off the road, such as dialing, locating a phone and texting, increase SCE risk to a greater extent than tasks that do not require eyes off the road such as talking. Although talking on a handheld device did not increase SCE risk, further research is required to determine whether it indirectly influences SCE risk (e.g., by encouraging other cell phone activities). In addition, a number of study biases and quality issues of naturalistic driving studies are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

    OpenAIRE

    Berndt, S.I.; Skibola, C.F.; Joseph, V.; Camp, N.J.; Nieters, A.; Wang, Z.; Cozen, W.; Monnereau, A.; Wang, S.S.; Kelly, R.S.; Lan, Q.; Teras, L.R.; Chatterjee, N.; Chung, C.C.; Yeager, M.

    2013-01-01

    Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10...

  11. Association between CD14 gene polymorphisms and cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jun Wang

    Full Text Available BACKGROUND: Two polymorphisms, -260C/T and -651C/T, in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. This meta-analysis aimed to investigate the association between the two polymorphisms and risk of cancer. METHODS: All eligible case-control studies published up to March 2014 were identified by searching PubMed, Web of Science, CNKI and WanFang database. Pooled odds ratio (OR with 95% confidence interval (CI were used to access the strength of this association in fixed- or random-effects model. RESULTS: 17 case-control studies from fourteen articles were included. Of those, there were 17 studies (4198 cases and 4194 controls for -260C/T polymorphism and three studies (832 cases and 1190 controls for -651C/T polymorphism. Overall, no significant associations between the two polymorphisms of CD14 gene and cancer risk were found. When stratified by ethnicity, cancer type and source of control, similar results were observed among them. In addition, in further subgroups analysis by Helicobacter pylori (H. pylori infection status and tumor location in gastric cancer subgroup, we found that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. CONCLUSIONS: This meta-analysis suggests that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. However, large and well-designed studies are warranted to validate our findings.

  12. A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis.

    Science.gov (United States)

    Peng, Wen-jia; Pan, Hai-feng; Tao, Jin-hui; Wang, Bing-xiang; Lu, Man-man; Wang, Song; He, Qian; Wang, Jing

    2012-09-01

    We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case-control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) -1722T/C, CTLA-4 -318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36-0.54; TT vs. TG + GG: OR 0.48, 95% CI 0.39-0.59; TT + TG vs. GG: OR 0.74, 95% CI 0.66-0.83; T vs. G: OR 0.72, 95% CI 0.66-0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.

  13. The Association Between Anxiety and Falls: A Meta-Analysis.

    Science.gov (United States)

    Hallford, David John; Nicholson, Geoff; Sanders, Kerrie; McCabe, Marita P

    2017-09-01

    Falls occur frequently among older adults and can lead to a range of adverse and debilitating outcomes. Although symptoms of clinical anxiety have been implicated as risk factors for falls, there is no current consensus on the empirical association between anxiety and falls. The current study aimed to address this gap in the literature by conducting a quantitative, meta-analytic review of findings from previous studies. A systematic literature search of bibliographic databases was conducted, yielding 18 studies that fit the criteria for inclusion in the meta-analysis. A random-effects model of all 18 studies showed a significant overall odds ratio of 1.53 (95% CI 1.28-1.83, p anxiety were associated with a 53% increased likelihood of falls. A high amount of variance among effect sizes was observed. Only age was identified as a moderator of this relationship in a subgroup of the samples. Clinical anxiety is associated with falls, however, further research is required to elucidate the factors that might moderate or mediate this relationship, the casual pathways through which they are related, and the associations between different types of anxiety and falls. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

    Science.gov (United States)

    Zhan, Qimin; Hu, Zhibin; He, Zhonghu; Jia, Weihua; Zhou, Yifeng; Yu, Kai; Shu, Xiao-Ou; Yuan, Jian-Min; Zheng, Wei; Zhao, Xue-Ke; Gao, She-Gan; Yuan, Zhi-Qing; Zhou, Fu-You; Fan, Zong-Min; Cui, Ji-Li; Lin, Hong-Li; Han, Xue-Na; Li, Bei; Chen, Xi; Dawsey, Sanford M.; Liao, Linda; Lee, Maxwell P.; Ding, Ti; Qiao, You-Lin; Liu, Zhihua; Liu, Yu; Yu, Dianke; Chang, Jiang; Wei, Lixuan; Gao, Yu-Tang; Koh, Woon-Puay; Xiang, Yong-Bing; Tang, Ze-Zhong; Fan, Jin-Hu; Han, Jing-Jing; Zhou, Sheng-Li; Zhang, Peng; Zhang, Dong-Yun; Yuan, Yuan; Huang, Ying; Liu, Chunling; Zhai, Kan; Qiao, Yan; Jin, Guangfu; Guo, Chuanhai; Fu, Jianhua; Miao, Xiaoping; Lu, Changdong; Yang, Haijun; Wang, Chaoyu; Wheeler, William A.; Gail, Mitchell; Yeager, Meredith; Yuenger, Jeff; Guo, Er-Tao; Li, Ai-Li; Zhang, Wei; Li, Xue-Min; Sun, Liang-Dan; Ma, Bao-Gen; Li, Yan; Tang, Sa; Peng, Xiu-Qing; Liu, Jing; Hutchinson, Amy; Jacobs, Kevin; Giffen, Carol; Burdette, Laurie; Fraumeni, Joseph F.; Shen, Hongbing; Ke, Yang; Zeng, Yixin; Wu, Tangchun; Kraft, Peter; Chung, Charles C.; Tucker, Margaret A.; Hou, Zhi-Chao; Liu, Ya-Li; Hu, Yan-Long; Liu, Yu; Wang, Li; Yuan, Guo; Chen, Li-Sha; Liu, Xiao; Ma, Teng; Meng, Hui; Sun, Li; Li, Xin-Min; Li, Xiu-Min; Ku, Jian-Wei; Zhou, Ying-Fa; Yang, Liu-Qin; Wang, Zhou; Li, Yin; Qige, Qirenwang; Yang, Wen-Jun; Lei, Guang-Yan; Chen, Long-Qi; Li, En-Min; Yuan, Ling; Yue, Wen-Bin; Wang, Ran; Wang, Lu-Wen; Fan, Xue-Ping; Zhu, Fang-Heng; Zhao, Wei-Xing; Mao, Yi-Min; Zhang, Mei; Xing, Guo-Lan; Li, Ji-Lin; Han, Min; Ren, Jing-Li; Liu, Bin; Ren, Shu-Wei; Kong, Qing-Peng; Li, Feng; Sheyhidin, Ilyar; Wei, Wu; Zhang, Yan-Rui; Feng, Chang-Wei; Wang, Jin; Yang, Yu-Hua; Hao, Hong-Zhang; Bao, Qi-De; Liu, Bao-Chi; Wu, Ai-Qun; Xie, Dong; Yang, Wan-Cai; Wang, Liang; Zhao, Xiao-Hang; Chen, Shu-Qing; Hong, Jun-Yan; Zhang, Xue-Jun; Freedman, Neal D; Goldstein, Alisa M.; Lin, Dongxin; Taylor, Philip R.; Wang, Li-Dong; Chanock, Stephen J.

    2014-01-01

    We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region. PMID:25129146

  15. A genome-wide association study of cognitive function in Chinese adult twins

    DEFF Research Database (Denmark)

    Xu, Chunsheng; Zhang, Dongfeng; Wu, Yili

    2017-01-01

    Multiple loci or genes have been identified using genome-wide association studies mainly in western countries but with inconsistent results. No similar studies have been conducted in the world's largest and rapidly aging Chinese population. The paper aimed to identify the specific genetic variants....... Gene-based analysis was performed on VEGAS2. The statistically significant genes were then subject to gene set enrichment analysis to further identify the specific biological pathways associated with cognitive function. No SNPs reached genome-wide significance although there were 13 SNPs of suggestive...

  16. Vitamin D deficiency in older adults and its associated factors: a cross-sectional analysis of the Mexican Health and Aging Study.

    Science.gov (United States)

    Carrillo-Vega, María Fernanda; García-Peña, Carmen; Gutiérrez-Robledo, Luis Miguel; Pérez-Zepeda, Mario Ulises

    2017-12-01

    Vitamin D deficiency was common in older adults from a country with adequate sun exposure. The variables associated with this deficiency provide insight into the next steps needed to characterize older adults with this deficiency and to treat it accordingly. The aim of this study was to describe the prevalence of and factors associated with vitamin D deficiency among Mexican older adults. This was a secondary analysis of the last wave of the Mexican Health and Aging Study. Vitamin D levels along with other biomarkers were obtained from a sub-sample of Mexican adults older than 60 years. Prevalence was described by sex and age group, and a multivariate analysis was performed to test the factors associated with this condition. Data from 1088 adults over the age of 60 years were analyzed. The mean serum vitamin D level was 23.1 ± 8.1 ng/mL and was significantly higher among men than women (25.6 ± 0.6 and 22.8 ± 0.5 ng/mL, respectively; p vitamin D deficiency, 65% of whom were women. Low 25-(OH)-vitamin D levels were associated with female sex (OR 1.74, 95% CI 1.59-2.42), current smoking (OR 2.21, 95% CI 1.47-3.39), education (OR 1.1, 95% CI 1.06-1.13), physical activity (OR 1.74, 95% CI 1.31-2.23), and high levels of glycated hemoglobin (OR 1.16, 95% CI 1.07-1.25). Vitamin D deficiency was highly prevalent in Mexican older adults and was associated with a number of factors, indicating the multifactorial causality of this deficiency.

  17. Adiponectin Concentrations: A Genome-wide Association Study

    Science.gov (United States)

    Jee, Sun Ha; Sull, Jae Woong; Lee, Jong-Eun; Shin, Chol; Park, Jongkeun; Kimm, Heejin; Cho, Eun-Young; Shin, Eun-Soon; Yun, Ji Eun; Park, Ji Wan; Kim, Sang Yeun; Lee, Sun Ju; Jee, Eun Jung; Baik, Inkyung; Kao, Linda; Yoon, Sungjoo Kim; Jang, Yangsoo; Beaty, Terri H.

    2010-01-01

    Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10−15 in the initial sample, p = 6.58 × 10−39 in the second genome-wide sample, and p = 2.12 × 10−32 in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10−83. The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10−58) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults. PMID:20887962

  18. Increased risk of venous thromboembolism associated with polymyositis and dermatomyositis: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Li Y

    2018-01-01

    Full Text Available Yanqing Li,1 Peihong Wang,2 Lei Li,3 Fei Wang,4 Yuxiu Liu5 1Department of Pharmacy Intravenous Admixture Services, Affiliated Hospital of Weifang Medical University, Weifang, 2Department of Interventional Oncology, Weifang Tumor Hospital, Weifang, 3Department of Gastroenterology, Affiliated Hospital of Weifang Medical University, Weifang, 4Department of Neurosurgery, Affiliated Hospital of Weifang Medical University, Weifang, 5School of Nursing, Weifang Medical University, Weifang, People’s Republic of China Objective: Polymyositis and dermatomyositis (PM/DM have been implicated in the development of venous thromboembolism (VTE. Previous studies investigating the association between PM/DM and VTE risk had yielded inconsistent findings. The aim of this study was to precisely estimate this association by meta-analysis of all available publications.Methods: Two investigators independently performed a comprehensive literature search in databases of PubMed, Embase, and the Cochrane Library for eligible studies. The strength for the association was weighed by pooled odds ratios (ORs with 95% confidence intervals (95% CIs. Stratified analysis and sensitivity analysis were performed for further analysis.Results: Six studies including 9,045 patients with PM/DM were analyzed. The pooled OR suggested that inflammatory myositis was associated with increased risk of VTE (OR =4.31, 95% CI: 2.55–7.29, P<0.001. Besides, significantly elevated risk of VTE was related with PM and DM, respectively (for PM: OR =6.87, 95% CI: 4.12–11.46, P<0.001; for DM: OR =11.59, 95% CI: 6.54–20.55, P<0.001. In addition, inflammatory myositis could increase the risk of DVT (OR =4.85, 95% CI: 1.38–17.12, P<0.05 and PE (OR =4.74, 95% CI: 2.18–10.30, P<0.05. Sensitivity analysis did not materially alter the pooled results.Conclusion: Our study shows strong evidence that patients with inflammatory myositis have an increased risk of VTE. Keywords: polymyositis

  19. Association between SERPING1 rs2511989 polymorphism and age-related macular degeneration: Meta-analysis

    Directory of Open Access Journals (Sweden)

    Yi Dong

    2015-04-01

    Full Text Available AIM: To investigate the association between SERPING1 rs2511989 (G>A polymorphism and age-related macular degeneration (AMD. METHODS: A number of electronic databases (up to July 15, 2014 were searched independently by two investigators. A Meta-analysis was performed on the association between SERPING1 rs2511989 polymorphism and AMD. Pooled odds ratios (ORs with 95% confidence intervals (CIs were estimated. RESULTS: Eight studies with 16 cohorts consisting of 9163 cases and 6813 controls were included in this Meta-analysis. There was no significant association between rs2511989 polymorphism and AMD under all genetic models in overall estimates (A vs G: OR= 0.938, 95%CI =0.858-1.025; AA vs GG:OR =0.871, 95%CI =0.719-1.056; AG vs GG: OR =0.944, 95%CI =0.845-1.054; AA+AG vs GG: OR =0.927, 95% CI =0.823-1.044; AA vs AG+GG: OR =0.890, 95%CI =0.780-1.034. Cumulative Meta-analyses also showed a trend of no association between rs2511989 polymorphism and AMD as information accumulated by year. Subgroup analysis and Meta-regression analysis indicated that age-matching status was the main source of heterogeneity. Sensitivity analysis found the results in overall comparisons and subgroup comparisons of white subjects under the allele model were found to have significantly statistical differences after studies deviating from Hardy-Weinberg equilibrium (HWE were excluded (overall: OR=0.918, 95%CI = 0.844-0.999, P =0.049; whites: OR =0.901, 95%CI = 0.817-0.994, P =0.038. However, the results were not sufficiently robust for further sensitivity analysis and statistical differences disappeared on applying Bonferroni correction (with a significance level set at 0.05/25. CONCLUSION: This Meta-analysis indicates that SERPING1 rs2511989 polymorphism and AMD tend to have no association with each other. Age matching status is a big confounding factor, and more studies with subtle designs are warranted in future.

  20. The association between uterine leiomyoma and placenta abruption: A meta-analysis.

    Science.gov (United States)

    Jenabi, Ensiyeh; Ebrahimzadeh Zagami, Samira

    2017-11-01

    Some epidemiological studies have found that uterine leiomyoma can increase the risk of placenta abruption. To date, the meta-analysis has not been performed for assessing the relationship between uterine leiomyoma and placenta abruption. This meta-analysis was conducted to estimate the association between uterine leiomyoma and the risk of placenta abruption. A literature search was conducted out in major databases PubMed, Web of Science, and Scopus from the earliest possible year to October 2016. The heterogeneity across studies was explored by Q-test and I 2 statistic. The publication bias was assessed by Begg's and Egger's tests. The results were showed using odds ratio (OR) estimate with its 95% confidence intervals (CI) using a random-effects model. The literature search included 953 articles until October 2016 with 232,024 participants. Based on OR estimates obtained from case-control and cohort studies, there was significant association between uterine leiomyoma and placenta abruption (2.63; 95% CI: 1.38, 3.88). We showed based on reports in observational studies that uterine leiomyoma is a risk factor for placenta abruption.

  1. Associations between interleukin-10 polymorphisms and susceptibility to juvenile idiopathic arthritis: a systematic review and meta-analysis.

    Science.gov (United States)

    Harsini, Sara; Saghazadeh, Amene; Nedjat, Saharnaz; Rezaei, Nima

    2018-03-01

    Cytokine genes, including interleukin-10 (IL-10), are known to play important roles in the pathogenesis of juvenile idiopathic arthritis (JIA). This study aims to determine whether the IL-10 polymorphisms confer susceptibility to JIA. A meta-analysis was performed on the associations between the IL-10 -1082 G/A, -592 C/A, and -819 C/T polymorphisms and JIA. A total number of 7 studies involving 1,785 patients and 6,142 controls were considered in the meta-analysis. Meta-analysis of the IL-10 -592 C/A and -819 C/T polymorphisms showed no association with JIA in the study participants, or in Caucasian or Middle Eastern participants. Meta-analysis of the IL-10 -1082 A allele in all study participants, Caucasian and Middle Eastern, showed significant associations with RA (overall ORs were 1.17, 1.15, and 1.41, respectively). Meta-analysis of the AA versus GG genotype of the IL-10 -1082 G/A polymorphism revealed significant associations with JIA (OR = 3.66, 95% CI = 1.44-9.29, P = 0.006) in participants from Middle Eastern countries. Additionally, meta-analysis of the GG versus AA+GA genotypes of the IL-10 -1082 G/A polymorphism revealed the GG genotype as the protective factor against JIA in the Middle Eastern subgroup (OR = 0.44, 95% CI = 0.20-0.94, P = 0,04). Moreover, meta-analysis of the IL-10 -1082 A allele in 4 studies on Hardy-Weinberg equilibrium showed a significant association with JIA (OR = 1.17, 95% CI = 1.07-1.28, P = 0.0009). No association was found between the IL-10 (-1082, -819, -592) ACC, ATA, and GCC haplotypes and JIA. These results suggest that the IL-10 -1082 G/A polymorphism confers susceptibility to JIA.

  2. Problems associated with dimensional analysis of electroencephalogram data

    Energy Technology Data Exchange (ETDEWEB)

    Layne, S.; Mayer-Kress, G.; Holzfuss, J.

    1985-01-01

    The goal was to evaluate anesthetic depth for a series of 5 to 10 patients by dimensional analysis. It has been very difficult to obtain clean EEG records from the operating room. Noise is prominent due to electrocautery and to movement of the patient's head by operating room personnel. In addition, specialized EEG equipment must be used to reduce noise and to accommodate limited space in the room. This report discusses problems associated with dimensional analysis of the EEG. We choose one EEG record from a single patient, in order to study the method but not to draw general conclusions. For simplicity, we consider only two states: awake but quiet, and medium anesthesia. 14 refs., 8 figs., 1 tab.

  3. DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta-analysis

    DEFF Research Database (Denmark)

    Veglia, Fabrizio; Loft, Steffen; Matullo, Giuseppe

    2008-01-01

    in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51-137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies......). The association was evident only in current smokers and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, whereas the results in never smokers were equivocal; in former smokers, no association......Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk...

  4. Association and linkage analysis of aluminum tolerance genes in maize.

    Directory of Open Access Journals (Sweden)

    Allison M Krill

    Full Text Available BACKGROUND: Aluminum (Al toxicity is a major worldwide constraint to crop productivity on acidic soils. Al becomes soluble at low pH, inhibiting root growth and severely reducing yields. Maize is an important staple food and commodity crop in acidic soil regions, especially in South America and Africa where these soils are very common. Al exclusion and intracellular tolerance have been suggested as two important mechanisms for Al tolerance in maize, but little is known about the underlying genetics. METHODOLOGY: An association panel of 282 diverse maize inbred lines and three F2 linkage populations with approximately 200 individuals each were used to study genetic variation in this complex trait. Al tolerance was measured as net root growth in nutrient solution under Al stress, which exhibited a wide range of variation between lines. Comparative and physiological genomics-based approaches were used to select 21 candidate genes for evaluation by association analysis. CONCLUSIONS: Six candidate genes had significant results from association analysis, but only four were confirmed by linkage analysis as putatively contributing to Al tolerance: Zea mays AltSB like (ZmASL, Zea mays aluminum-activated malate transporter2 (ALMT2, S-adenosyl-L-homocysteinase (SAHH, and Malic Enzyme (ME. These four candidate genes are high priority subjects for follow-up biochemical and physiological studies on the mechanisms of Al tolerance in maize. Immediately, elite haplotype-specific molecular markers can be developed for these four genes and used for efficient marker-assisted selection of superior alleles in Al tolerance maize breeding programs.

  5. AB126. Association between FOX03A gene polymorphisms and human longevity: a meta-analysis

    Science.gov (United States)

    Zhao, Shanchao; Bao, Jiming; Song, Xianlu

    2016-01-01

    Objective Numerous studies have shown associations between the FOX03A gene, encoding the forkhead box 03 transcription factor, and human or specifically male longevity. However, the associations of specific FOX03A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. Methods A comprehensive search was conducted to identify studies of FOX03A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (Cls) were calculated by comparing the minor and major alleles. Results A total of seven articles reporting associations of FOX03A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rsI3217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR =1.36, 95% CI, 1. 10–1.69, P=0.005; OR =1.20, 95% CI, 1.04–1.37, P=0.01; OR =1.27, 95% CI, 1.10–1.46, P=0.001; OR =1.14, 95% CI, 1.01–1.27 and OR =1.24, 95% CI, 1.07–1.43, P=0.003, respectively). Analysis is stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR =1.54, 95% CI, 1.33–1.79, P<0.001; OR =1.38, 95% CI, 1.15–1.66, P=0.001; and OR =1.39, 95% CI, 1.15–1.67, P=0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. Conclusions In conclusion, this meta-analysis indicates a significant association of five FOX03A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

  6. Latent class analysis of multimorbidity patterns and associated outcomes in Spanish older adults: a prospective cohort study.

    Science.gov (United States)

    Olaya, Beatriz; Moneta, Maria Victoria; Caballero, Francisco Félix; Tyrovolas, Stefanos; Bayes, Ivet; Ayuso-Mateos, José Luis; Haro, Josep Maria

    2017-08-18

    This study sought to identify multimorbidity patterns and determine the association between these latent classes with several outcomes, including health, functioning, disability, quality of life and use of services, at baseline and after 3 years of follow-up. We analyzed data from a representative Spanish cohort of 3541 non-institutionalized people aged 50 years old and over. Measures were taken at baseline and after 3 years of follow-up. Latent Class Analysis (LCA) was conducted using eleven common chronic conditions. Generalized linear models were conducted to determine the adjusted association of multimorbidity latent classes with several outcomes. 63.8% of participants were assigned to the "healthy" class, with minimum disease, 30% were classified under the "metabolic/stroke" class and 6% were assigned to the "cardiorespiratory/mental/arthritis" class. Significant cross-sectional associations were found between membership of both multimorbidity classes and poorer memory, quality of life, greater burden and more use of services. After 3 years of follow-up, the "metabolic/stroke" class was a significant predictor of lower levels of verbal fluency while the two multimorbidity classes predicted poor quality of life, problems in independent living, higher risk of hospitalization and greater use of health services. Common chronic conditions in older people cluster together in broad categories. These broad clusters are qualitatively distinct and are important predictors of several health and functioning outcomes. Future studies are needed to understand underlying mechanisms and common risk factors for patterns of multimorbidity and to propose more effective treatments.

  7. Association Analysis Suggests SOD2 as a Newly Identified Candidate Gene Associated With Leprosy Susceptibility.

    Science.gov (United States)

    Ramos, Geovana Brotto; Salomão, Heloisa; Francio, Angela Schneider; Fava, Vinícius Medeiros; Werneck, Renata Iani; Mira, Marcelo Távora

    2016-08-01

    Genetic studies have identified several genes and genomic regions contributing to the control of host susceptibility to leprosy. Here, we test variants of the positional and functional candidate gene SOD2 for association with leprosy in 2 independent population samples. Family-based analysis revealed an association between leprosy and allele G of marker rs295340 (P = .042) and borderline evidence of an association between leprosy and alleles C and A of markers rs4880 (P = .077) and rs5746136 (P = .071), respectively. Findings were validated in an independent case-control sample for markers rs295340 (P = .049) and rs4880 (P = .038). These results suggest SOD2 as a newly identified gene conferring susceptibility to leprosy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  8. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

    DEFF Research Database (Denmark)

    Jones, Gregory T; Tromp, Gerard; Kuivaniemi, Helena

    2017-01-01

    studies (GWAS). Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new...... associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. The 4 new risk loci for AAA appear to be specific for AAA compared with other...

  9. The association between prostatitis and prostate cancer. Systematic review and meta-analysis.

    Science.gov (United States)

    Perletti, Gianpaolo; Monti, Elena; Magri, Vittorio; Cai, Tommaso; Cleves, Anne; Trinchieri, Alberto; Montanari, Emanuele

    2017-12-31

    The main outcome of this review was the association between a history of clinical chronic prostatitis (NIH category II or III) and a histologically confirmed diagnosis of prostate cancer. Crude odds ratios and 95% confidence intervals (CI) were calculated to analyze dichotomous data. For analysis of pooled data we adopted a random-effects model and the inverse variance weighing method. Heterogeneity was assessed by calculating the I2 value. Out of 2794 screened records, we retrieved 16 full-text articles written in English, reporting the data of 15 case-control studies, involving 422.943 patients. Pooled analysis resulted in a significant crude odds ratio of 1.83 (95% CI: 1.43 to 2.35; P ratio was 2.12 (95% CI: 1.38 to 3.22). According to GRADE criteria, the overall quality of the meta-analysis data is low, mainly due to the presence of bias, confounders and extreme effect size outliers. Five among the included studies reported data assessed in 8015 African-American subjects. Pooled analysis resulted in a non-significant crude odds ratio of 1.59 (95% CI: 0.71 to 3.57; P = 0.26), and considerable heterogeneity (I2 = 90%). Meta-analysis of 15 case-control studies shows that a history of clinical chronic prostatitis can significantly increase the odds for prostate cancer in the general population, whereas such association in African-American individuals remains uncertain.

  10. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis

    Science.gov (United States)

    You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

    2016-01-01

    Background Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. Methods We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Results Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68–0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50–0.92) and flavonols (RR = 0.68, 95% CI = 0.58–0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71–1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger’s test (p = 0.26). Conclusions This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted. PMID:26960146

  11. Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.

    Directory of Open Access Journals (Sweden)

    Elizabeth G Holliday

    Full Text Available Genetic factors explain a majority of risk variance for age-related macular degeneration (AMD. While genome-wide association studies (GWAS for late AMD implicate genes in complement, inflammatory and lipid pathways, the genetic architecture of early AMD has been relatively under studied. We conducted a GWAS meta-analysis of early AMD, including 4,089 individuals with prevalent signs of early AMD (soft drusen and/or retinal pigment epithelial changes and 20,453 individuals without these signs. For various published late AMD risk loci, we also compared effect sizes between early and late AMD using an additional 484 individuals with prevalent late AMD. GWAS meta-analysis confirmed previously reported association of variants at the complement factor H (CFH (peak P = 1.5×10(-31 and age-related maculopathy susceptibility 2 (ARMS2 (P = 4.3×10(-24 loci, and suggested Apolipoprotein E (ApoE polymorphisms (rs2075650; P = 1.1×10(-6 associated with early AMD. Other possible loci that did not reach GWAS significance included variants in the zinc finger protein gene GLI3 (rs2049622; P = 8.9×10(-6 and upstream of GLI2 (rs6721654; P = 6.5×10(-6, encoding retinal Sonic hedgehog signalling regulators, and in the tyrosinase (TYR gene (rs621313; P = 3.5×10(-6, involved in melanin biosynthesis. For a range of published, late AMD risk loci, estimated effect sizes were significantly lower for early than late AMD. This study confirms the involvement of multiple established AMD risk variants in early AMD, but suggests weaker genetic effects on the risk of early AMD relative to late AMD. Several biological processes were suggested to be potentially specific for early AMD, including pathways regulating RPE cell melanin content and signalling pathways potentially involved in retinal regeneration, generating hypotheses for further investigation.

  12. Night Shift Work and Risk of Depression: Meta-analysis of Observational Studies.

    Science.gov (United States)

    Lee, Aeyoung; Myung, Seung Kwon; Cho, Jung Jin; Jung, Yu Jin; Yoon, Jong Lull; Kim, Mee Young

    2017-07-01

    This study aimed to assess whether night shift work is associated with the risk of depression by using a meta-analysis of observational studies. We searched PubMed and EMBASE in August, 2016 to locate eligible studies and investigated the association between night shift work and the risk of depression, reporting outcome measures with adjusted odds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs). In the meta-analysis of a total of 11 observational studies with 9 cross-sectional study, 1 longitudinal study, and 1 cohort study, night shift work was significantly associated with an increased risk of depression (OR/RR, 1.43; 95% CI, 1.24-1.64; I² = 78.0%). Also, subgroup meta-analyses by gender, night shift work duration, type of occupation, continent, and type of publication showed that night shift work was consistently associated with the increased risk of depression. The current meta-analysis suggests that night shift work is associated with the increased risk of depression. However, further large prospective cohort studies are needed to confirm this association. © 2017 The Korean Academy of Medical Sciences.

  13. Short-term association between ambient air pollution and pneumonia in children: A systematic review and meta-analysis of time-series and case-crossover studies.

    Science.gov (United States)

    Nhung, Nguyen Thi Trang; Amini, Heresh; Schindler, Christian; Kutlar Joss, Meltem; Dien, Tran Minh; Probst-Hensch, Nicole; Perez, Laura; Künzli, Nino

    2017-11-01

    Ambient air pollution has been associated with respiratory diseases in children. However, its effects on pediatric pneumonia have not been meta-analyzed. We conducted a systematic review and meta-analysis of the short-term association between ambient air pollution and hospitalization of children due to pneumonia. We searched the Web of Science and PubMed for indexed publications up to January 2017. Pollutant-specific excess risk percentage (ER%) and confidence intervals (CI) were estimated using random effect models for particulate matter (PM) with diameter ≤ 10 (PM 10 ) and ≤2.5 μm (PM 2.5 ), sulfur dioxide (SO 2 ), ozone (O 3 ), nitrogen dioxide (NO 2 ), and carbon monoxide (CO). Results were further stratified by subgroups (children under five, emergency visits versus hospital admissions, income level of study location, and exposure period). Seventeen studies were included in the meta-analysis. The ER% per 10 μg/m 3 increase of pollutants was 1.5% (95% CI: 0.6%-2.4%) for PM 10 and 1.8% (95% CI: 0.5%-3.1%) for PM 2.5 . The corresponding values per 10 ppb increment of gaseous pollutants were 2.9% (95% CI: 0.4%-5.3%) for SO 2 , 1.7% (95% CI: 0.5%-2.8%) for O 3 , and 1.4% (95% CI: 0.4%-2.4%) for NO 2 . ER% per 1000 ppb increment of CO was 0.9% (95% CI: 0.0%-1.9%). Associations were not substantially different between subgroups. This meta-analysis shows a positive association between daily levels of ambient air pollution markers and hospitalization of children due to pneumonia. However, lack of studies from low-and middle-income countries limits the quantitative generalizability given that susceptibilities to the adverse effects of air pollution may be different in those populations. The meta-regression in our analysis further demonstrated a strong effect of country income level on heterogeneity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Male pattern baldness and its association with coronary heart disease: a meta-analysis

    Science.gov (United States)

    Yamada, Tomohide; Hara, Kazuo; Umematsu, Hitomi; Kadowaki, Takashi

    2013-01-01

    Objective To confirm the association between male pattern baldness and coronary heart disease (CHD). Design Meta-analysis of observational studies. Data sources Medline and the Cochrane Library were searched for articles published up to November 2012 using keywords that included both ‘baldness’ and ‘coronary heart disease’ and the reference lists of those studies identified were also searched. Study selection Observational studies were identified that reported risk estimates for CHD related to baldness. Two observers independently assessed eligibility, extracted data and assessed the possibility of bias. Data synthesis The adjusted relative risk (RR) and 95% CI were estimated using the DerSimonian-Laird random-effect model. Results 850 possible studies, 3 cohort studies and 3 case–control studies were selected (36 990 participants). In the cohort studies, the adjusted RR of men with severe baldness for CHD was 1.32 (95% CI 1.08 to 1.63, p=0.008, I2=25%) compared to those without baldness. Analysis of younger men (baldness (RR 1.44, 95% CI 1.11 to 1.86, p=0.006, I2=0%). In three studies employing the modified Hamilton scale, vertex baldness was associated with CHD and the relation depended on the severity of baldness (severe vertex: RR 1.48 (1.04 to 2.11, p=0.03); moderate vertex: RR 1.36 (1.16 to 1.58, pbaldness was not associated with CHD (RR 1.11 (0.92 to 1.32, p=0.28)). Conclusions Vertex baldness, but not frontal baldness, is associated with an increased risk of CHD. The association with CHD depends on the severity of vertex baldness and also exists among younger men. Thus, vertex baldness might be more closely related to atherosclerosis than frontal baldness, but the association between male pattern baldness and CHD deserves further investigation. PMID:23554099

  15. Genetics of Obesity Traits: A Bivariate Genome-Wide Association Analysis

    DEFF Research Database (Denmark)

    Wu, Yili; Duan, Haiping; Tian, Xiaocao

    2018-01-01

    Previous genome-wide association studies on anthropometric measurements have identified more than 100 related loci, but only a small portion of heritability in obesity was explained. Here we present a bivariate twin study to look for the genetic variants associated with body mass index and waist......-hip ratio, and to explore the obesity-related pathways in Northern Han Chinese. Cholesky decompositionmodel for 242monozygotic and 140 dizygotic twin pairs indicated a moderate genetic correlation (r = 0.53, 95%CI: 0.42–0.64) between body mass index and waist-hip ratio. Bivariate genome-wide association.......05. Expression quantitative trait loci analysis identified rs2242044 as a significant cis-eQTL in both the normal adipose-subcutaneous (P = 1.7 × 10−9) and adipose-visceral (P = 4.4 × 10−15) tissue. These findings may provide an important entry point to unravel genetic pleiotropy in obesity traits....

  16. Association of estrogen receptor α PvuII and XbaI polymorphisms with prostate cancer susceptibility and risk stratification: a meta-analysis from case-control studies

    Directory of Open Access Journals (Sweden)

    Zhao YN

    2017-06-01

    Full Text Available Yining Zhao,1,* Xi Zheng,2,* Lijie Zhang,3 Qiang Hu,3 Yitian Guo,3 Hua Jiang,3 Shennan Shi,4 Xiang Zhang1 1Department of Urology, Qilu Hospital of Shandong University, Jinan, 2Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 3Department of Urology, Affiliated Zhongda Hospital, Medical School, Southeast University, Nanjing, 4Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Background: Studies on the association between two single nucleotide polymorphisms (SNPs in estrogen receptor α (ERα, PvuII (rs2234693 T>C and XbaI (rs9340799 A>G, and the prostate cancer risk are inconsistent. Therefore, we performed a meta-analysis to derive a more accurate estimation of this relationship. Methods: A literature search of PubMed, Embase, Web of Science databases until October 1, 2016, was conducted. Crude odds ratios (ORs with 95% confidence intervals (CIs were calculated to assess the strength of this association. Results: Eighteen case-control studies, with a total of 3,317 prostate cancer patients and 8,324 controls, were included. Results showed that both PvuII and XbaI polymorphisms were significantly associated with a higher prostate cancer risk in overall populations. To derive a more accurate estimation, subgroup analysis stratified by ethnicity revealed that this relationship existed only in Caucasians, but not in Asians. Furthermore, PvuII polymorphism was significantly associated with high Gleason grade (Gleason score ≥7 cancers. Conclusion: The current meta-analysis demonstrates that ERα PvuII and XbaI polymorphisms are associated with a higher prostate cancer risk in Caucasians, but not in Asians, and PvuII polymorphism is significantly associated with high Gleason grade tumors, indicating the probability of inherited susceptibility to prostate cancer arising from different genomic ERα SNPs

  17. Characteristics of cyclist crashes in Italy using latent class analysis and association rule mining.

    Directory of Open Access Journals (Sweden)

    Gabriele Prati

    Full Text Available The factors associated with severity of the bicycle crashes may differ across different bicycle crash patterns. Therefore, it is important to identify distinct bicycle crash patterns with homogeneous attributes. The current study aimed at identifying subgroups of bicycle crashes in Italy and analyzing separately the different bicycle crash types. The present study focused on bicycle crashes that occurred in Italy during the period between 2011 and 2013. We analyzed categorical indicators corresponding to the characteristics of infrastructure (road type, road signage, and location type, road user (i.e., opponent vehicle and cyclist's maneuver, type of collision, age and gender of the cyclist, vehicle (type of opponent vehicle, and the environmental and time period variables (time of the day, day of the week, season, pavement condition, and weather. To identify homogenous subgroups of bicycle crashes, we used latent class analysis. Using latent class analysis, the bicycle crash data set was segmented into 19 classes, which represents 19 different bicycle crash types. Logistic regression analysis was used to identify the association between class membership and severity of the bicycle crashes. Finally, association rules were conducted for each of the latent classes to uncover the factors associated with an increased likelihood of severity. Association rules highlighted different crash characteristics associated with an increased likelihood of severity for each of the 19 bicycle crash types.

  18. Association between HIV/AIDS and multi-drug resistance tuberculosis: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yonatan Moges Mesfin

    Full Text Available BACKGROUND: Human immunodeficiency virus (HIV, multi-drug resistant tuberculosis (MDR is emerging as major challenge facing tuberculosis control programs worldwide particularly in Asia and Africa. Findings from different studies on associations of HIV co-infection and drug resistance among patients with TB have been contradictory (discordant. Some institution based studies found strongly increased risks for multi-drug resistant TB (MDR TB among patients co-infected with TB and HIV, whereas other studies found no increased risk (it remains less clear in community based studies. The aim was to conduct a systematic review and meta-analysis of the association between multi-drug resistant tuberculosis and HIV infection. METHODS AND FINDINGS: Systematic review of the published literature of observational studies was conducted. Original studies were identified using databases of Medline/Pubmed, Google Scholar and HINARI. The descriptions of original studies were made using frequency and forest plot. Publication bias was assessed using Funnel plot graphically and Egger weighted and Begg rank regression tests statistically. Heterogeneity across studies was checked using Cochrane Q test statistic and I(2. Pool risk estimates of MDR-TB and sub-grouping analysis were computed to analyze associations with HIV. Random effects of the meta-analysis of all 24 observational studies showed that HIV is associated with a marginal increased risk of multi-drug resistant tuberculosis (estimated Pooled OR 1.24; 95%, 1.04-1.43. Subgroup analyses showed that effect estimates were higher (Pooled OR 2.28; 95%, 1.52-3.04 for primary multi-drug resistance tuberculosis and moderate association between HIV/AIDS and MDR-TB among population based studies and no significant association in institution settings. CONCLUSIONS: This study demonstrated that there is association between MDR-TB and HIV. Capacity for diagnosis of MDR-TB and initiating and scale up of antiretroviral

  19. AB126. Association between FOX03A gene polymorphisms and human longevity: a meta-analysis

    OpenAIRE

    Zhao, Shanchao; Bao, Jiming; Song, Xianlu

    2016-01-01

    Objective Numerous studies have shown associations between the FOX03A gene, encoding the forkhead box 03 transcription factor, and human or specifically male longevity. However, the associations of specific FOX03A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. Methods A comprehensive search was conducted to identify studies of FOX03A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% c...

  20. PAI-1 -675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study.

    Science.gov (United States)

    Xu, Kuanfeng; Liu, Xiaoyun; Yang, Fan; Cui, Dai; Shi, Yun; Shen, Chong; Tang, Wei; Yang, Tao

    2013-01-01

    A meta-analysis was performed to assess the association between the PAI-1 -675 4G/5G polymorphism and susceptibility to diabetes mellitus (DM), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic coronary artery disease (CAD). A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further stratified analyses and sensitivity analyses were also performed. Publication bias was examined by the modified Begg's and Egger's test. Twenty published articles with twenty-seven outcomes were included in the meta-analysis: 6 studies with a total of 1,333 cases and 3,011 controls were analyzed for the PAI-1 -675 4G/5G polymorphism with diabetes risk, 7 studies with 1,060 cases and 1,139 controls for DN risk, 10 studies with 1,327 cases and 1,557 controls for DR and 4 studies with 610 cases and 1,042 controls for diabetic CAD risk respectively. Using allelic comparison (4G vs. 5G), the PAI-1 -675 4G/5G polymorphism was observed to have no significant association with diabetes (REM OR 1.07, 95% CI 0.96, 1.20), DN (REM OR 1.10, 95% CI 0.98, 1.25), DR (REM OR 1.09, 95% CI 0.97, 1.22) or diabetic CAD risk (REM OR 1.07, 95% CI 0.81, 1.42), and similar results were obtained in the dominant, recessive and co-dominant models. Our meta-analyses suggest that the PAI-1 -675 4G/5G polymorphism might not be a risk factor for DM, DN, DR or diabetic CAD risk in the populations investigated. This conclusion warrants confirmation by further studies.

  1. Efficient Integrative Multi-SNP Association Analysis via Deterministic Approximation of Posteriors.

    Science.gov (United States)

    Wen, Xiaoquan; Lee, Yeji; Luca, Francesca; Pique-Regi, Roger

    2016-06-02

    With the increasing availability of functional genomic data, incorporating genomic annotations into genetic association analysis has become a standard procedure. However, the existing methods often lack rigor and/or computational efficiency and consequently do not maximize the utility of functional annotations. In this paper, we propose a rigorous inference procedure to perform integrative association analysis incorporating genomic annotations for both traditional GWASs and emerging molecular QTL mapping studies. In particular, we propose an algorithm, named deterministic approximation of posteriors (DAP), which enables highly efficient and accurate joint enrichment analysis and identification of multiple causal variants. We use a series of simulation studies to highlight the power and computational efficiency of our proposed approach and further demonstrate it by analyzing the cross-population eQTL data from the GEUVADIS project and the multi-tissue eQTL data from the GTEx project. In particular, we find that genetic variants predicted to disrupt transcription factor binding sites are enriched in cis-eQTLs across all tissues. Moreover, the enrichment estimates obtained across the tissues are correlated with the cell types for which the annotations are derived. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  2. Association between erectile dysfunction and chronic periodontitis: A clinical study

    Directory of Open Access Journals (Sweden)

    Ranjit Singh Uppal

    2014-01-01

    Conclusion: It may be concluded that chronic periodontitis and ED are associated with each other. However, further large scale studies with confounder analysis and longitudinal follow-up are warranted to explore the link between these two diseases.

  3. Revealing the association between cerebrovascular accidents and ambient temperature: a meta-analysis

    Science.gov (United States)

    Zorrilla-Vaca, Andrés; Healy, Ryan Jacob; Silva-Medina, Melissa M.

    2017-05-01

    The association between cerebrovascular accidents (CVA) and weather has been described across several studies showing multiple conflicting results. In this paper, we aim to conduct a meta-analysis to further clarify this association, as well as to find the potential sources of heterogeneity. PubMed, EMBASE, and Google Scholar were searched from inception through 2015, for articles analyzing the correlation between the incidence of CVA and temperature. A pooled effect size (ES) was estimated using random effects model and expressed as absolute values. Subgroup analyses by type of CVA were also performed. Heterogeneity and influence of covariates—including geographic latitude of the study site, male percentage, average temperature, and time interval—were assessed by meta-regression analysis. Twenty-six articles underwent full data extraction and scoring. A total of 19,736 subjects with CVA from 12 different countries were included and grouped as ischemic strokes (IS; n = 14,199), intracerebral hemorrhages (ICH; n = 3798), and subarachnoid hemorrhages (SAH; n = 1739). Lower ambient temperature was significantly associated with increase in incidence of overall CVA when using unadjusted (pooled ES = 0.23, P < 0.001) and adjusted data (pooled ES = 0.03, P = 0.003). Subgroup analyses showed that lower temperature has higher impact on the incidence of ICH (pooled ES = 0.34, P < 0.001), than that of IS (pooled ES = 0.22, P < 0.001) and SAH (pooled ES = 0.11, P = 0.012). In meta-regression analysis, the geographic latitude of the study site was the most influencing factor on this association ( Z-score = 8.68). Synthesis of the existing data provides evidence supporting that a lower ambient temperature increases the incidence of CVA. Further population-based studies conducted at negative latitudes are needed to clarify the influence of this factor.

  4. Prevalence and associated factors for early interruption of exclusive breastfeeding: meta-analysis on Brazilian epidemiological studies

    Directory of Open Access Journals (Sweden)

    Marcos Pereira-Santos

    Full Text Available Abstract Objectives: to summarize Brazilian studies that analyzed the risk factors for Exclusive Breastfeeding (EBF interruption before the child's six months of life. Methods: systematic review and meta-analysis indexed articles from Bireme, Scielo and Pubmed databases published in the period of January 2000 to December 2015. Results: 22 articles were included in the meta-analysis. The factors related to newborns were observed, such as birth weight (OR= 1.17; CI 95%: 1.05-1.29, female gender (OR= 1,09; CI 95%: 1.04-1.13 and the use of pacifier (OR= 2.29; CI 95%: 1.68-2.91 were the main factors responsible for the increase in the occurrence of EBF interruption. The factors were related to the mother, maternal age below twenty years old (OR= 1.22; CI 95%: 1.12-1.33 low schooling level (OR=1.28; CI 95%: 1.11-1.45, primiparity (OR= 1.17; CI 95%: 1.02-1.32 maternal employment during the postpartum period (OR= 1.26; CI 95%: 1.11-1.41, and low family income (OR= 1.22; CI 95%: 1.08-1.37 contributed significantly to the EBF interruption . Conclusions: the meta-analysis of Brazilian epidemiological studies demonstrated evidences to conclude that below the age of twenty, low schooling, primiparity, maternal employment in the postpartum period and low family income are associated to the interruption of exclusive breastfeeding until 6 months of age. Children with low birth weight, female gender and used a pacifier had greater vulnerability to not be exclusively breastfed. In conclusion, most of these factors can be modified through appropriate public policies throughout the adequate prenatal period to promote exclusive breastfeeding.

  5. Genome-wide association analysis identifies 13 new risk loci for schizophrenia

    NARCIS (Netherlands)

    Ripke, S.; O'Dushlaine, C.; Chambert, K.; Moran, J.L.; Kähler, A.K.; Akterin, S.; Bergen, S.E.; Collins, A.L.; Crowley, J.J.; Fromer, M.; Kim, Y.; Lee, S.H.; Magnusson, P.K.; Sanchez, N.; Stahl, E.A.; Williams, S.; Wray, N.R.; Xia, K.; Bettella, F.; Borglum, A. D.; Bulik-Sullivan, B.K.; Cormican, P.; Craddock, N.; de Leeuw, C.A.; Durmishi, N.; Gill, M.; Golimbet, V.; Hamshere, M.L.; Holmans, P.; Hougaard, D. M.; Kendler, K.S.; Lin, K.; Morris, D. W.; Mors, O.; Mortensen, P.B.; Neale, B. M.; O'Neill, F. A.; Owen, M.J.; Milovancevic, M.P.; Posthuma, D.; Powell, J.; Richards, A.L.; Riley, B.P.; Ruderfer, D.; Rujescu, D.; Sigurdsson, E.; Silagadze, T.; Smit, A.B.; Stefansson, H.; Steinberg, S.; Suvisaari, J.; Tosato, S.; Verhage, M.; Walters, T.J.; Levinson, D.F.; Gejman, P.V.; Laurent, C.; Mowry, B. J.; O'Donovan, M.C.; Pulver, A. E.; Schwab, S.G.; Wildenauer, D. B.; Dudbridge, F.; Shi, J.; Albus, M.; Alexander, M.; Campion, D.; Cohen, D.; Dikeos, D.; Duan, J.; Eichhammer, P.; Godard, S.; Hansen, M.; Lerer, F.B.; Liang, K.Y.; Maier, W.; Mallet, J.; Nertney, D. A.; Nestadt, G.; Norton, N.; O'Neill, F.A.; Papadimitriou, G.N.; Ribble, R.; Sanders, A.R.; Silverman, J.M.; Wormley, B.; Arranz, M.J.; Bakker, S.; Bender, S.; Bramon, E.; Collier, D.; Crespo-Facorro, B.; Hall, J.; Iyegbe, C.; Jablensky, A.; Kahn, R.S.; Kalaydjieva, L.; Lawrie, S.M.; Lewis, C.M.; Linszen, D.H.; Mata, I.; McIntosh, A.; Murray, R.M.; Ophoff, R.A.; van Os, J.; Walshe, M.; Weisbrod, M.; Wiersma, D.; Donnely, P.; Barasso, I.; Blackwell, J.M.; Brown, M.A.; Casas, J.P.; Corvin, A.P.; Deloukas, P.; Duncanson, A.; Jankowski, J.; Markus, H.S.; Mathew, C.G.; Palmer, C.N.; Plomin, R.; Rautanen, A.; Sawcer, S.J.; Trembath, R.C.; Viswanathan, A.C.; Wood, N.W.; Spencer, C. C.; Band, G.; Bellenguez, C.; Freeman, C.; Hellenthal, G.; Giannoulatou, E.; Pirinen, M.; Pearson, R.D.; Strange, A.; Su, Z.; Vukcevic, D.; Langford, C.; Hunt, S.E.; Edkins, S.; Gwilliam, R.; Blackburn, H.; Bumpstead, S.; Dronov, S.; Gillman, M.; Gray, E.; Hammond, N.; Jayakumar, A.; McCann, O.T.; Liddle, J.; Potter, S.C.; Ravindrarajah, R.; Ricketts, M.; Tashakkori-Ghanbaria, A.; Waller, M.J.; Weston, P.; Widaa, S.; Whittaker, P.; Barrroso, I.; McCarthy, M.I.; Spencer, C.C.; Stefansson, K.; Scolnick, E.; Purcell, S.; McCarroll, S.A.; Sklar, P.; Hultman, C. M.; Sullivan, P.F.

    2013-01-01

    Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-Analysis with

  6. Genome-wide association analysis identifies 13 new risk loci for schizophrenia

    NARCIS (Netherlands)

    Ripke, Stephan; O'Dushlaine, Colm; Chambert, Kimberly; Moran, Jennifer L.; Kähler, Anna K.; Akterin, Susanne; Bergen, Sarah E.; Collins, Ann L.; Crowley, James J.; Fromer, Menachem; Kim, Yunjung; Lee, Sang Hong; Magnusson, Patrik K. E.; Sanchez, Nick; Stahl, Eli A.; Williams, Stephanie; Wray, Naomi R.; Xia, Kai; Bettella, Francesco; Borglum, Anders D.; Bulik-Sullivan, Brendan K.; Cormican, Paul; Craddock, Nick; de Leeuw, Christiaan; Durmishi, Naser; Gill, Michael; Golimbet, Vera; Hamshere, Marian L.; Holmans, Peter; Hougaard, David M.; Kendler, Kenneth S.; Lin, Kuang; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Neale, Benjamin M.; O'Neill, Francis A.; Owen, Michael J.; Milovancevic, Milica Pejovic; Posthuma, Danielle; Powell, John; Richards, Alexander L.; Riley, Brien P.; Ruderfer, Douglas; Rujescu, Dan; Sigurdsson, Engilbert; Silagadze, Teimuraz; Smit, August B.; Stefansson, Hreinn; Steinberg, Stacy; Suvisaari, Jaana; Tosato, Sarah; Verhage, Matthijs; Walters, James T.; Levinson, Douglas F.; Gejman, Pablo V.; Laurent, Claudine; Mowry, Bryan J.; O'Donovan, Michael C.; Pulver, Ann E.; Schwab, Sibylle G.; Wildenauer, Dieter B.; Dudbridge, Frank; Shi, Jianxin; Albus, Margot; Alexander, Madeline; Campion, Dominique; Cohen, David; Dikeos, Dimitris; Duan, Jubao; Eichhammer, Peter; Godard, Stephanie; Hansen, Mark; Lerer, F. Bernard; Liang, Kung-Yee; Maier, Wolfgang; Mallet, Jacques; Nertney, Deborah A.; Nestadt, Gerald; Norton, Nadine; Papadimitriou, George N.; Ribble, Robert; Sanders, Alan R.; Silverman, Jeremy M.; Walsh, Dermot; Williams, Nigel M.; Wormley, Brandon; Arranz, Maria J.; Bakker, Steven; Bender, Stephan; Bramon, Elvira; Collier, David; Crespo-Facorro, Benedicto; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, Rene S.; Kalaydjieva, Luba; Lawrie, Stephen; Lewis, Cathryn M.; Linszen, Don H.; Mata, Ignacio; McIntosh, Andrew; Murray, Robin M.; Ophoff, Roel A.; van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Wiersma, Durk; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden P.; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C. A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard D.; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Tashakkori-Ghanbaria, Avazeh; Waller, Matthew J.; Weston, Paul; Widaa, Sara; Whittaker, Pamela; McCarthy, Mark I.; Stefansson, Kari; Scolnick, Edward; Purcell, Shaun; McCarroll, Steven A.; Sklar, Pamela; Hultman, Christina M.; Sullivan, Patrick F.

    2013-01-01

    Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with

  7. Association studies in common endocrine diseases (review article

    Directory of Open Access Journals (Sweden)

    Akrami SM

    2007-05-01

    Full Text Available Our understanding of the pathogenesis of endocrine disorders increase rapidly by genetic studies at the molecular level. Common endocrine disorders such as diabetes mellitus, obesity, osteoporosis, dyslipidemia and cancer follow the multifactorial model in the genetic aspect. This review tries to clarify the approach in molecular studies of such diseases for clinicians in different specialties. How to evaluate a possible association between a single nucleotide polymorphism and an endocrinopathy or its complication is the main concern of this review. Two approaches for gene mapping will be discussed as well as main challenges regarding each approach. All such genetic studies ideally include some test of the association between genome sequence variation and the phenotype of interest such as the trait itself, the presence of a given complication, or measures of some endocrinopathy-related intermediate trait. Despite different advances in this analysis, there are major concerns regarding the overall performance and robustness of genetic association studies. By using powerful new high-throughput methods, further insights to molecular basis of such endocrine disorders can be expected. Close correlation between geneticists and clinicians can effectively bridge between basic sciences and clinical investigations.

  8. A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

    NARCIS (Netherlands)

    Siddiq, Afshan; Couch, Fergus J.; Chen, Gary K.; Lindström, Sara; Eccles, Diana; Millikan, Robert C.; Michailidou, Kyriaki; Stram, Daniel O.; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B.; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Berg, Christine D.; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M.; Buring, Julie E.; Buys, Saundra S.; Campa, Daniele; Carpenter, Jane E.; Chasman, Daniel I.; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S.; Czene, Kamila; Deming, Sandra L.; Diasio, Robert B.; Diver, W. Ryan; Dunning, Alison M.; Durcan, Lorraine; Ekici, Arif B.; Fasching, Peter A.; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D.; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M.; Gerty, Susan M.; Rodriguez-Gil, Jorge L.; Giles, Graham G.; van Gils, Carla H.; Godwin, Andrew K.; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E.; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N.; Hopper, John L.; Hu, Jennifer J.; Huntsman, Scott; Ingles, Sue A.; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B.; John, Esther M.; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N.; Coetzee, Gerhard A.; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M.; Lee, I.-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G.; McLean, Catriona A.; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R.; Montgomery, Grant W.; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J.; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J.; Palmer, Julie R.; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F.; Schmutzler, Rita K.; Slager, Susan; Southey, Melissa C.; Stevens, Kristen N.; Sinn, Hans-Peter; Press, Michael F.; Ross, Eric; Riboli, Elio; Ridker, Paul M.; Schumacher, Fredrick R.; Severi, Gianluca; dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J.; Thun, Michael J.; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, Joellen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R.; van den Berg, David; Zheng, Wei; Ziegler, Regina G.; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F.; Hunter, David J.; Henderson, Brian E.; Chanock, Stephen J.; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A.; Vachon, Celine M.

    2012-01-01

    Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of

  9. Periodontal disease and risk of preeclampsia: a meta-analysis of observational studies.

    Directory of Open Access Journals (Sweden)

    Ben-Juan Wei

    Full Text Available BACKGROUND: Many epidemiological studies have found a positive association between periodontal disease (PD and the risk of preeclampsia, but the magnitude of this association varies and independent studies have reported conflicting findings. We performed a meta-analysis to ascertain the relationship between PD and preeclampsia. METHODS: The PubMed database was searched up to January 12, 2013, for relevant observational studies on an association between PD and the risk of preeclampsia. Data were extracted and analyzed independently by two authors. The meta-analysis was performed using comprehensive meta-analysis software. RESULTS: Thirteen observational case-control studies and two cohort studies, involving 1089 preeclampsia patients, were identified. Based on a random-effects meta-analysis, a significant association between PD and preeclampsia was identified (odds ratio = 2.79, 95% confidence interval CI, 2.01-3.01, P<0.0001. CONCLUSIONS: Although the causality remains unclear, the association between PD and preeclampsia may reflect the induction of PD by the preeclamptic state, or it may be part of an overall exaggerated inflammatory response to pregnancy. Larger randomized controlled trials with preeclampsia as the primary outcome and pathophysiological studies are required to explore causality and to dissect the biological mechanisms involved.

  10. Genome-wide association study identifies five new schizophrenia loci

    NARCIS (Netherlands)

    Ripke, S.; Sanders, A. R.; Kendler, K. S.; Levinson, D. F.; Sklar, P.; Holmans, P. A.; Lin, D. Y.; Duan, J.; Ophoff, R. A.; Andreassen, O. A.; Scolnick, E.; Cichon, S.; St Clair, D.; Corvin, A.; Gurling, H.; Werge, T.; Rujescu, D.; Blackwood, D. H.; Pato, C. N.; Malhotra, A. K.; Purcell, S.; Dudbridge, F.; Neale, B. M.; Rossin, L.; Visscher, P. M.; Posthuma, D.; Ruderfer, D. M.; Fanous, A.; Stefansson, H.; Steinberg, S.; Mowry, B. J.; Golimbet, V.; de Hert, M.; Jonsson, E. G.; Bitter, I.; Pietilainen, O. P.; Collier, D. A.; Tosato, S.; Agartz, I.; Albus, M.; Alexander, M.; Amdur, R. L.; Amin, F.; Bass, N.; Bergen, S. E.; Black, D. W.; Borglum, A. D.; Brown, M. A.; Bruggeman, R.; Buccola, N. G.; Byerley, W. F.; Cahn, W.; Cantor, R. M.; Carr, V. J.; Catts, S. V.; Choudhury, K.; Cloninger, C. R.; Cormican, P.; Craddock, N.; Danoy, P. A.; Datta, S.; de Haan, L.; Demontis, D.; Dikeos, D.; Djurovic, S.; Donnely, P.; Donohoe, G.; Duong, L.; Dwyer, S.; Fink-Jensen, A.; Freedman, R.; Freimer, N. B.; Friedl, M.; Georgieva, L.; Giegling, I.; Gill, M.; Glenthoj, B.; Godard, S.; Hamshere, M.; Hansen, M.; Hartmann, A. M.; Henskens, F. A.; Hougaard, D. M.; Hultman, C. M.; Ingason, A.; Jablensky, A. V.; Jakobsen, K. D.; Jay, M.; Jurgens, G.; Kahn, R. S.; Keller, M. C.; Kenis, G.; Kenny, E.; Kim, Y.; Kirov, G. K.; Konnerth, H.; Konte, B.; Krabbendam, L.; Krasucki, R.; Lasseter, V. K.; Laurent, C.; Lawrence, J.; Lencz, T.; Lerer, F. B.; Liang, K. Y.; Lichtenstein, P.; Lieberman, J. A.; Linszen, D. H.; Lonnqvist, J.; Loughland, C. M.; Maclean, A. W.; Maher, B. S.; Maier, W.; Mallet, J.; Malloy, P.; Mattheisen, M.; Mattingsdal, M.; McGhee, K. A.; McGrath, J. J.; McIntosh, A.; McLean, D. E.; McQuillin, A.; Melle, I.; Michie, P. T.; Milanova, V.; Morris, D. W.; Mors, O.; Mortensen, P. B.; Moskvina, V.; Muglia, P.; Myin-Germeys, I.; Nertney, D. A.; Nestadt, G.; Nielsen, J.; Nikolov, I.; Nordentoft, M.; Norton, N.; Nothen, M. M.; O'Dushlaine, C. T.; Olincy, A.; Olsen, L.; O'Neill, F. A.; Orntoft, T. F.; Owen, M. J.; Pantelis, C.; Papadimitriou, G.; Pato, M. T.; Peltonen, L.; Petursson, H.; Pickard, B.; Pimm, J.; Pulver, A. E.; Puri, V.; Quested, D.; Quinn, E. M.; Rasmussen, H. B.; Rethelyi, J. M.; Ribble, R.; Rietschel, M.; Riley, B. P.; Ruggeri, M.; Schall, U.; Schulze, T. G.; Schwab, S. G.; Scott, R. J.; Shi, J.; Sigurdsson, E.; Silvermann, J. M.; Spencer, C. C.; Stefansson, K.; Strange, A.; Strengman, E.; Stroup, T. S.; Suvisaari, J.; Terenius, L.; Thirumalai, S.; Thygesen, J. H.; Timm, S.; Toncheva, D.; van den Oord, E.; van Os, J.; van Winkel, R.; Veldink, J.; Walsh, D.; Wang, A. G.; Wiersma, D.; Wildenauer, D. B.; Williams, H. J.; Williams, N. M.; Wormley, B.; Zammit, S.; Sullivan, P. F.; O'Donovan, M. C.; Daly, M. J.; Gejman, P. V.

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded

  11. Genome-Wide Association Study of Serum Selenium Concentrations

    Directory of Open Access Journals (Sweden)

    Ulrike Peters

    2013-05-01

    Full Text Available Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO Cancer Screening and the Women’s Health Initiative (WHI. We tested association between 2,474,333 single nucleotide polymorphisms (SNPs and serum selenium concentrations using linear regression models. In the first stage (PLCO 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003 in the second stage (WHI. Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11 and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI. Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.

  12. Susceptibility to chronic mucus hypersecretion, a genome wide association study.

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    Akkelies E Dijkstra

    Full Text Available Chronic mucus hypersecretion (CMH is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA study of CMH in Caucasian populations.GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years. Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP.A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6, OR = 1.17, located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1 on chromosome 3. The risk allele (G was associated with higher mRNA expression of SATB1 (4.3×10(-9 in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

  13. Relationships between Association of Research Libraries (ARL) Statistics and Bibliometric Indicators: A Principal Components Analysis

    Science.gov (United States)

    Hendrix, Dean

    2010-01-01

    This study analyzed 2005-2006 Web of Science bibliometric data from institutions belonging to the Association of Research Libraries (ARL) and corresponding ARL statistics to find any associations between indicators from the two data sets. Principal components analysis on 36 variables from 103 universities revealed obvious associations between…

  14. The Association Between Maternal Subclinical Hypothyroidism and Growth, Development, and Childhood Intelligence: A Meta-analysis

    Science.gov (United States)

    Liu, Yahong; Chen, Hui; Jing, Chen; Li, FuPin

    2018-06-01

    To explore the association between maternal subclinical hypothyroidism (SCH) in pregnancy and the somatic and intellectual development of their offspring. Using RevMan 5.3 software, a meta-analysis of cohort studies published from inception to May 2017, focusing on the association between maternal SCH in pregnancy and childhood growth, development and intelligence, was performed. Sources included the Cochrane Library, Pub-Med, Web of Science, China National Knowledge Infrastructure and Wan Fang Data. Analysis of a total of 15 cohort studies involving 1.896 pregnant women with SCH revealed that SCH in pregnancy was significantly associated with the intelligence (p=0.0007) and motor development (pdevelopment, low birth weight, premature delivery, fetal distress and fetal growth restriction.

  15. Efficacy of Acupuncture for Psychological Symptoms Associated with Opioid Addiction: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Zhang Boyuan

    2014-01-01

    Full Text Available This review systematically assessed the clinical evidence for and against acupuncture as a treatment for psychological symptoms associated with opioid addiction. The database was accessed from MEDLINE and China Knowledge Resource Integrated Database. We included all randomized clinical trials published in Chinese and English regardless of their controls. Meta-analysis was performed using the RevMan software, version 5.2. We conducted a literature search of 16 databases from their inception to January 2014. Four studies from Western countries did not report any clinical gains in the treatment of psychological symptoms associated with opioid addiction. 10 of 12 studies from China have reported positive findings regarding the use of acupuncture to treat the psychological symptoms associated with opioid addiction. The methodological quality of the included studies was poor. The meta-analysis indicated that there was a significant difference between the treatment group and the control group for anxiety and depression associated with opioid addiction, although groups did not differ on opioid craving. This review and meta-analysis could not confirm that acupuncture was an effective treatment for psychological symptoms associated with opioid addiction. However, considering the potential of acupuncture demonstrated in the included studies, further rigorous randomized controlled trials with long followup are warranted.

  16. Factors associated with adolescent cigarette smoking in Greece: results from a cross sectional study (GYTS Study).

    Science.gov (United States)

    Rachiotis, George; Muula, Adamson S; Rudatsikira, Emmanuel; Siziya, Seter; Kyrlesi, Athina; Gourgoulianis, Konstantinos; Hadjichristodoulou, Christos

    2008-09-15

    Data about the predictors of smoking among adolescents in Greece are sparse. We tried to identify factors associated with current cigarette smoking among in-school adolescents in Greece in the context of GYTS study. A secondary analysis of data from a questionnaire study using the Global Youth Tobacco Survey methodology was conducted to identify factors associated with smoking among adolescents in Greece. Data were collected in 2004-2005. The outcome variable was cigarette smoking within the past 30 days preceding the survey while independent variables included age, gender, parental educational status, parental smoking, perception of harmfulness of smoking, and the amount of pocket money at the adolescent's disposal. 6141 adolescents (51.5% males and 48.5% females) participated in the study. In multivariate analysis, cigarette smoking was associated with male gender (OR: 1.62; 95% CI: 1, 08-3.08), parental smoking (OR: 2.59; 95% CI: 1.45-5.89), and having pocket money > or = 16 Euros (OR: 2.64; 95% CI: 1.19-5.98). Male gender, parental smoking, and having pocket-money > or = 16 Euros were independently associated with current smoking among Greek students. These findings could be taken into account in order to formulate a comprehensive anti-smoking strategy in Greece.

  17. Systematic review and meta-analysis of Spanish studies regarding the association between maternal 25-hydroxyvitamin D levels and perinatal outcomes.

    Science.gov (United States)

    Martínez-Domínguez, Samuel J; Tajada, Mauricio; Chedraui, Peter; Pérez-López, Faustino R

    2018-05-29

    This systematic review and meta-analysis of Spanish studies assessed the association of maternal 25-hydroxyvitamin D [25(OH)D] levels on perinatal outcomes. PubMed, Cochrane Library, Embase, Scielo, Scopus, and Web of Science research databases were searched from inception through December 30 2017 using the terms 'vitamin D', 'pregnancy', and 'Spain'. Studies that compared first or second half of pregnancy normal 25(OH)D (≥30.0 ng/mL) versus insufficient (20.0-29.9 ng/mL) or deficient (D levels. In addition, second half of pregnancy 25(OH) levels did not affect birthweight. Maternal 25(OH)D levels during pregnancy did not affect studied perinatal outcomes and birthweight.

  18. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    NARCIS (Netherlands)

    J.F. Felix (Janine); J.P. Bradfield (Jonathan); C. Monnereau; R.J.P. van der Valk (Ralf); E. Stergiakouli (Evie); A. Chesi (Alessandra); R. Gaillard (Romy); B. Feenstra (Bjarke); E. Thiering (Elisabeth); E. Kreiner-Møller (Eskil); A. Mahajan (Anubha); Niina Pitkänen; R. Joro (Raimo); A. Cavadino (Alana); V. Huikari (Ville); S. Franks (Steve); M. Groen-Blokhuis (Maria); D.L. Cousminer (Diana); J.A. Marsh (Julie); T. Lehtimäki (Terho); J.A. Curtin (John); J. Vioque (Jesus); T.S. Ahluwalia (Tarunveer Singh); R. Myhre (Ronny); T.S. Price (Thomas); Natalia Vilor-Tejedor; L. Yengo (Loic); N. Grarup (Niels); I. Ntalla (Ioanna); W.Q. Ang (Wei); M. Atalay (Mustafa); H. Bisgaard (Hans); A.I.F. Blakemore (Alexandra); A. Bonnefond (Amélie); L. Carstensen (Lisbeth); J.G. Eriksson (Johan G.); C. Flexeder (Claudia); L. Franke (Lude); F. Geller (Frank); M. Geserick (Mandy); A.L. Hartikainen; C.M.A. Haworth (Claire M.); J.N. Hirschhorn (Joel N.); A. Hofman (Albert); J.-C. Holm (Jens-Christian); M. Horikoshi (Momoko); J.J. Hottenga (Jouke Jan); J. Huang (Jian); H.N. Kadarmideen (Haja N.); M. Kähönen (Mika); W. Kiess (Wieland); T.A. Lakka (Timo); T.A. Lakka (Timo); A. Lewin (Alex); L. Liang (Liming); L.-P. Lyytikäinen (Leo-Pekka); B. Ma (Baoshan); P. Magnus (Per); S.E. McCormack (Shana E.); G. Mcmahon (George); F.D. Mentch (Frank); C.M. Middeldorp (Christel); C.S. Murray (Clare S.); K. Pahkala (Katja); T.H. Pers (Tune); R. Pfäffle (Roland); D.S. Postma (Dirkje); C. Power (Christine); A. Simpson (Angela); V. Sengpiel (Verena); C. Tiesler (Carla); M. Torrent (Maties); A.G. Uitterlinden (André); J.B.J. van Meurs (Joyce); R. Vinding (Rebecca); J. Waage (Johannes); J. Wardle (Jane); E. Zeggini (Eleftheria); B.S. Zemel (Babette S.); G.V. Dedoussis (George); O. Pedersen (Oluf); P. Froguel (Philippe); J. Sunyer (Jordi); R. Plomin (Robert); B. Jacobsson (Bo); T. Hansen (Torben); J.R. Gonzalez (Juan R.); A. Custovic; O.T. Raitakari (Olli T.); C.E. Pennell (Craig); Elisabeth Widén; D.I. Boomsma (Dorret); G.H. Koppelman (Gerard); S. Sebert (Sylvain); M.-R. Jarvelin (Marjo-Riitta); E. Hypponen (Elina); M.I. McCarthy (Mark); V. Lindi (Virpi); N. Harri (Niinikoski); A. Körner (Antje); K. Bønnelykke (Klaus); J. Heinrich (Joachim); M. Melbye (Mads); F. Rivadeneira Ramirez (Fernando); H. Hakonarson (Hakon); S.M. Ring (Susan); G.D. Smith; T.I.A. Sørensen (Thorkild I.A.); N.J. Timpson (Nicholas); S.F.A. Grant (Struan); V.W.V. Jaddoe (Vincent); H.J. Kalkwarf (Heidi J.); J.M. Lappe (Joan M.); V. Gilsanz (Vicente); S.E. Oberfield (Sharon E.); J.A. Shepherd (John A.); A. Kelly (Andrea)

    2016-01-01

    textabstractA large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation

  19. Associations between neighbourhood characteristics, body mass index and health-related behaviours of adolescents in the Kiel Obesity Prevention Study: a multilevel analysis.

    Science.gov (United States)

    Lange, D; Wahrendorf, M; Siegrist, J; Plachta-Danielzik, S; Landsberg, B; Müller, M J

    2011-06-01

    To understand determinants of overweight, several studies addressed the association between neighbourhood characteristics and adult obesity. However, little is known about the association of such characteristics with adolescents' overweight. This study aims at the influence of neighbourhood characteristics on adolescent body mass index (BMI) and lifestyle and to what extent BMI and lifestyle variation between neighbourhoods can be explained by neighbourhood characteristics. We used cross-sectional data from the Kiel Obesity Prevention Study collected between 2004 and 2008 in 28 different residential districts of the city of Kiel (North Germany). Anthropometric data were available for 1675 boys and 1765 girls (n=3440) aged 13-15 years, and individual lifestyle factors and sociodemographic data were included in the analysis. At the macro level, six different neighbourhood characteristics were used: unemployment rate, population density, traffic density, prevalence of energy-dense food supply, number of sports fields and parks, and crime rate. To test our main hypothesis, linear and logistic multilevel regression analyses were performed to predict BMI and lifestyle factors in individuals nested in neighbourhoods. Findings of multilevel analysis show little between-neighbourhood variations in BMI and health-related behaviours. In all, 2% of BMI variation, 4% of media time variation and 3% of variation in snacking behaviour could be attributed to differences in neighbourhoods. Environmental factors are significantly associated with adolescent BMI and health-related behaviour; however, their total effect is small. Owing to these results, recommendations for structural policy measures as part of prevention of overweight in adolescents must be made cautiously.

  20. HFE gene C282Y variant is associated with colorectal cancer in Caucasians: a meta-analysis.

    Science.gov (United States)

    Chen, Weidong; Zhao, Hua; Li, Tiegang; Yao, Hongliang

    2013-08-01

    The HFE gene has been suggested to play an important role in the pathogenesis of colorectal cancer. However, the results have been conflicting. In this study, we performed a meta-analysis to clarify the association of HFE gene C282Y variant with colorectal cancer. PubMed and Embase were retrieved to identify the potential literature. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. A total of eight papers including nine studies (7,588 colorectal cancer cases and 81,571 controls) for HFE gene C282Y variant were included in the meta-analysis. The result indicated that HFE gene C282Y variant was significantly associated with colorectal cancer under recessive model (OR = 2.00, 95 % CI = 1.32-3.04), with no evidence of between-study heterogeneity (I (2) = 0.2 %, p = 0.432). Further subgroup analysis by number of cases suggested the effect was significant in studies with more than 500 cases (OR = 2.51, 95 % CI = 1.58-3.98, I (2) = 0.0 %, p = 0.921), but not in studies with less than 500 cases (OR = 0.75, 95 % CI = 0.28-1.97, I (2) = 0.0 %, p = 0.622). The current meta-analysis supported the positive association of HFE gene C282Y variant with colorectal cancer. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

  1. Recommendations for using standardised phenotypes in genetic association studies

    Directory of Open Access Journals (Sweden)

    Naylor Melissa G

    2009-07-01

    Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  2. Association between asthma and dysphonia: A population-based study.

    Science.gov (United States)

    Park, Bumjung; Choi, Hyo Geun

    2016-09-01

    We investigated whether asthma predisposes patients to organic laryngeal lesions or increases dysphonia in those without organic laryngeal lesions. We performed a cross-sectional study with data from the Korea National Health and Nutrition Examination Survey; 19,330 subjects from 2008 through 2011 were included. The associations of asthma with organic laryngeal lesions and dysphonia were analyzed using a simple/multiple logistic regression analysis with complex sampling while adjusting for confounding factors (age, sex, smoking status, stress level, and body mass index) that could contribute to dysphonia. Compared with non-asthma participants, the asthma patients tended to be older and female and to have higher stress levels. These factors were associated with dysphonia (Age, AOR = 1.20, 95% CI = 1.14 = 1.23, P dysphonia. Compared with non-asthma participants, asthma patients who had not taken asthma medication recently showed a higher AOR (1.62; 95% CI = 1.0-2.42) for dysphonia, and asthma patients who had taken asthma medication recently showed the highest adjusted odds ratio for dysphonia (AOR = 1.97; 95% confidence interval, CI = 1.28-3.02, P = 0.001). On multiple logistic regression analysis, vocal nodules, laryngeal polyps, and laryngitis were not associated with asthma (all P > 0.05). Asthma patients are predisposed to subjective dysphonia due to demographic and clinical characteristics (older age, female, and higher stress level) as well as to asthma itself. However, asthma was not associated with organic laryngeal lesions in this study.

  3. Association between Breastfeeding and Endometrial Cancer Risk: Evidence from a Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Lianlian Wang

    2015-07-01

    Full Text Available Quantification of the association between breastfeeding and risk of endometrial cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between breastfeeding and endometrial cancer risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge through April 2015. A random effect model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationships were assessed by restricted cubic spline and variance-weighted least squares regression analysis. Fourteen articles involving 5158 endometrial cancer cases and 706,946 participants were included in this meta-analysis. Pooled results suggested that breastfeeding significantly reduced the risk of endometrial cancer (summary relative risk (RR: 0.77, 95% CI: 0.62–0.96, I2: 63.0%, especially in North America (summary RR: 0.87, 95% CI: 0.79–0.95. A linear dose-response relationship was found, with the risk of endometrial cancer decreased by 2% for every one-month increase in the duration of breastfeeding (summary RR: 0.98, 95% CI: 0.97–0.99. Our analysis suggested that breastfeeding, particularly a longer duration of breastfeeding, was inversely associated with the risk of endometrial cancer, especially in North America, but not in Europe and Asia, probably due to the small number of cases included. Due to this limitation, further studies originating in other countries are required to assess the association between breastfeeding and endometrial cancer risk.

  4. Association of sleep bruxism with ceramic restoration failure: A systematic review and meta-analysis.

    Science.gov (United States)

    de Souza Melo, Gilberto; Batistella, Elis Ângela; Bertazzo-Silveira, Eduardo; Simek Vega Gonçalves, Thais Marques; Mendes de Souza, Beatriz Dulcineia; Porporatti, André Luís; Flores-Mir, Carlos; De Luca Canto, Graziela

    2018-03-01

    Ceramic restorations are popular because of their excellent optical properties. However, failures are still a major concern, and dentists are confronted with the following question: is sleep bruxism (SB) associated with an increased frequency of ceramic restoration failures? The purpose of this systematic review and meta-analysis was to assess whether the presence of SB is associated with increased ceramic restoration failure. Observational studies and clinical trials that evaluated the short- and long-term survival rate of ceramic restorations in SB participants were selected. Sleep bruxism diagnostic criteria must have included at least 1 of the following: questionnaire, clinical evaluation, or polysomnography. Seven databases, in addition to 3 nonpeer-reviewed literature databases, were searched. The risk of bias was assessed by using the meta-analysis of statistics assessment and review instrument (MAStARI) checklist. Eight studies were included for qualitative synthesis, but only 5 for the meta-analysis. Three studies were categorized as moderate risk and 5 as high risk of bias. Clinical and methodological heterogeneity across studies were considered high. Increased hazard ratio (HR=7.74; 95% confidence interval [CI]=2.50 to 23.95) and odds ratio (OR=2.52; 95% CI=1.24 to 5.12) were observed considering only anterior ceramic veneers. Nevertheless, limited data from the meta-analysis and from the restricted number of included studies suggested that differences in the overall odds of failure concerning SB and other types of ceramic restorations did not favor or disfavor any association (OR=1.10; 95% CI=0.43 to 2.8). The overall quality of evidence was considered very low according to the GRADE criteria. Within the limitations of this systematic review, the overall result from the meta-analysis did not favor any association between SB and increased odds of failure for ceramic restorations. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry

  5. A genome-wide association meta-analysis identifies new childhood obesity loci

    Science.gov (United States)

    Bradfield, Jonathan P.; Taal, H. Rob; Timpson, Nicholas J.; Scherag, André; Lecoeur, Cecile; Warrington, Nicole M.; Hypponen, Elina; Holst, Claus; Valcarcel, Beatriz; Thiering, Elisabeth; Salem, Rany M.; Schumacher, Fredrick R.; Cousminer, Diana L.; Sleiman, Patrick M.A.; Zhao, Jianhua; Berkowitz, Robert I.; Vimaleswaran, Karani S.; Jarick, Ivonne; Pennell, Craig E.; Evans, David M.; St. Pourcain, Beate; Berry, Diane J.; Mook-Kanamori, Dennis O; Hofman, Albert; Rivadeinera, Fernando; Uitterlinden, André G.; van Duijn, Cornelia M.; van der Valk, Ralf J.P.; de Jongste, Johan C.; Postma, Dirkje S.; Boomsma, Dorret I.; Gauderman, William J.; Hassanein, Mohamed T.; Lindgren, Cecilia M.; Mägi, Reedik; Boreham, Colin A.G.; Neville, Charlotte E.; Moreno, Luis A.; Elliott, Paul; Pouta, Anneli; Hartikainen, Anna-Liisa; Li, Mingyao; Raitakari, Olli; Lehtimäki, Terho; Eriksson, Johan G.; Palotie, Aarno; Dallongeville, Jean; Das, Shikta; Deloukas, Panos; McMahon, George; Ring, Susan M.; Kemp, John P.; Buxton, Jessica L.; Blakemore, Alexandra I.F.; Bustamante, Mariona; Guxens, Mònica; Hirschhorn, Joel N.; Gillman, Matthew W.; Kreiner-Møller, Eskil; Bisgaard, Hans; Gilliland, Frank D.; Heinrich, Joachim; Wheeler, Eleanor; Barroso, Inês; O'Rahilly, Stephen; Meirhaeghe, Aline; Sørensen, Thorkild I.A.; Power, Chris; Palmer, Lyle J.; Hinney, Anke; Widen, Elisabeth; Farooqi, I. Sadaf; McCarthy, Mark I.; Froguel, Philippe; Meyre, David; Hebebrand, Johannes; Jarvelin, Marjo-Riitta; Jaddoe, Vincent W.V.; Smith, George Davey; Hakonarson, Hakon; Grant, Struan F.A.

    2012-01-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight novel signals yielding association with P < 5×10−6 in to nine independent datasets (n = 2,818 cases and 4,083 controls) we observed two loci that yielded a genome wide significant combined P-value, namely near OLFM4 on 13q14 (rs9568856; P=1.82×10−9; OR=1.22) and within HOXB5 on 17q21 (rs9299; P=3.54×10−9; OR=1.14). Both loci continued to show association when including two extreme childhood obesity cohorts (n = 2,214 cases and 2,674 controls). Finally, these two loci yielded directionally consistent associations in the GIANT meta-analysis of adult BMI1. PMID:22484627

  6. Functional linear models for association analysis of quantitative traits.

    Science.gov (United States)

    Fan, Ruzong; Wang, Yifan; Mills, James L; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao

    2013-11-01

    Functional linear models are developed in this paper for testing associations between quantitative traits and genetic variants, which can be rare variants or common variants or the combination of the two. By treating multiple genetic variants of an individual in a human population as a realization of a stochastic process, the genome of an individual in a chromosome region is a continuum of sequence data rather than discrete observations. The genome of an individual is viewed as a stochastic function that contains both linkage and linkage disequilibrium (LD) information of the genetic markers. By using techniques of functional data analysis, both fixed and mixed effect functional linear models are built to test the association between quantitative traits and genetic variants adjusting for covariates. After extensive simulation analysis, it is shown that the F-distributed tests of the proposed fixed effect functional linear models have higher power than that of sequence kernel association test (SKAT) and its optimal unified test (SKAT-O) for three scenarios in most cases: (1) the causal variants are all rare, (2) the causal variants are both rare and common, and (3) the causal variants are common. The superior performance of the fixed effect functional linear models is most likely due to its optimal utilization of both genetic linkage and LD information of multiple genetic variants in a genome and similarity among different individuals, while SKAT and SKAT-O only model the similarities and pairwise LD but do not model linkage and higher order LD information sufficiently. In addition, the proposed fixed effect models generate accurate type I error rates in simulation studies. We also show that the functional kernel score tests of the proposed mixed effect functional linear models are preferable in candidate gene analysis and small sample problems. The methods are applied to analyze three biochemical traits in data from the Trinity Students Study. © 2013 WILEY

  7. Molecular analysis of childhood primitive neuroectodermal tumors defines markers associated with poor outcome

    DEFF Research Database (Denmark)

    Scheurlen, W G; Schwabe, G C; Joos, S

    1998-01-01

    PURPOSE: The diagnostic and prognostic significance of well-defined molecular markers was investigated in childhood primitive neuroectodermal tumors (PNET). MATERIALS AND METHODS: Using microsatellite analysis, Southern blot analysis, and fluorescence in situ hybridization (FISH), 30 primary tumors......: In our study, amplification of c-myc was a poor-prognosis marker in PNET. LOH of chromosome 17p was associated with metastatic disease. Molecular analysis of primary tumors using these markers may be useful for stratification of children with PNET in future prospective studies. The other aberrations...... investigated were not of significant prognostic value, but may provide an entry point for future large-scale molecular studies....

  8. Association of Healthy Habits Beliefs and Mortality in Older Adults: A Longitudinal Analysis of the Mexican Health and Aging Study.

    Science.gov (United States)

    Fernandez-Villa, Julio M; Marquez, David X; Sanchez-Garrido, Natalia; Perez-Zepeda, Mario U; Gonzalez-Lara, Mariana

    2017-06-01

    The aim of this article is to establish the association between beliefs about healthy habits and mortality in a group of Mexican older adults. This is an 11-year follow-up secondary analysis of the Mexican Health and Aging Study. There was a significant difference ( p healthy habits have the potential to improve health compared with those who did not. After adjustment for confounders, Cox regression models showed a hazard ratio (HR) of 0.17 (95% confidence interval [CI] [0.07, 0.38], p healthy habits. Although the mechanism is not completely clear, according to our results, believing that healthy habits can improve health was associated with lower rates of mortality. Further research should elucidate potential strategies for changing beliefs in older adults with the goal of improving their overall health.

  9. The association between non-Hodgkin lymphoma and organophosphate pesticides exposure: A meta-analysis

    International Nuclear Information System (INIS)

    Hu, Liqin; Luo, Dan; Zhou, Tingting; Tao, Yun; Feng, Jingwen; Mei, Surong

    2017-01-01

    Several epidemiological studies show the association between organophosphate pesticides (OPs) and the risk of non-Hodgkin lymphoma (NHL), yet various research results remain controversial. To explore the hazard of OPs exposure to human health, three kinds of OPs (Terbufos, Malathion, and Diazinon) that are non-halogenated aliphatic compounds were included in the meta-analysis. We searched PubMed and Web of Science Databases for articles published from 1985 to February 2017. The databases were also searched for eligible studies through a manual references search. The random-effect model was utilized to compute the odds ratios (ORs) and 95% confident intervals (CIs). A total of ten observational studies (five cohort, four case-control, and one nested case-control) were included in our meta-analysis, with a pooled OR of 1.22 (95% CI 1.04 to 1.43) of Malathion, Terbufos and Diazinion. The general heterogeneity for OR was moderate (P h  = 0.032, I 2  = 41.2%). The OR estimates in the subset analyses were utilized to compare the association between the three kinds of OPs and NHL; Terbufos (OR = 1.07, 95% CI 0.85 to 1.36) and Malathion (OR = 1.17, 95% CI 0.82 to 1.67) had a statistically non-significant relationship, whereas Diazinon (OR = 1.39, 95% CI 1.11 to 1.73) was significantly associated with an increased NHL risk. Because immune dysfunction was thought to increase NHL risk, the toxicity levels in the immune system of the three types of OPs were compared. Malathion attacked immune cells via a direct effect and Diazinon disrupted the neuro-immune system, which involves the cholinergic system of lymphocytes via indirect immune damage, whereas an immunotoxic effect involving Terbufos was not reported. Overall, the present meta-analysis indicated a statistically significant association between Diazinon exposure and NHL risk. - Highlights: • The present meta-analysis indicated a significantly positive association between Diazinon exposure and NHL risk.

  10. Association between the rs1143634 polymorphism in interleukin-1B and chronic periodontitis: Results from a meta-analysis composed by 54 case/control studies.

    Science.gov (United States)

    da Silva, Felipe Rodolfo Pereira; Vasconcelos, Any Carolina Cardoso Guimarães; de Carvalho França, Luiz Felipe; Di Lenardo, David; Nascimento, Hélio Mateus Silva; Vasconcelos, Daniel Fernando Pereira

    2018-08-20

    Several factors are involved in the periodontitis with host response through cytokines and as well as with influence of polymorphisms in cytokine genes, however the results remained contradictory. This study aimed at evaluating the rs1143634 polymorphism in interleukin-1B gene, a cytokine gene, and the risk of chronic periodontitis with conducting a meta-analysis focusing in ethnicity. A review in literature was performed in several databases to studies published before June 2017. Data extraction was performed by two calibrated investigators and the calculations of the meta-analysis were obtained through Review Manager version 5.2 statistical software with Odds Ratio (OR) calculation and Funnel plot (P  0.05). No publication bias was found in allelic evaluation. This meta-analysis in 9376 participants with 54 case/control studies revealed the rs1143634 polymorphism was associated with elevated risk of chronic periodontitis in overall analysis as well as Caucasian and Asian ethnicities and Mixed population. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Early-life nutritional status and metabolic syndrome: gender-specific associations from a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    Science.gov (United States)

    Briskiewicz, Bruna Lucas; Barreto, Sandhi Maria; do Amaral, Joana Ferreira; Diniz, Maria de Fátima Haueisen Sander; Molina, Maria Del Carmen Bisi; Matos, Sheila Maria Alvim; Cardoso, Letícia de Oliveira; Velasquez-Melendez, Gustavo; Schmidt, Maria Inês; Giatti, Luana

    2018-06-01

    In the present study we investigated gender-specific associations of low birth weight (LBW) and shorter relative leg length with metabolic syndrome (MetS) after adjusting for sociodemographic characteristics and health-related behaviours. We also investigated whether these associations are independent of age at menarche and BMI at 20 years old. Cross-sectional analysis. Baseline data from 12 602 participants (35-74 years) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), 2008-2010. MetS was defined according to the revised National Cholesterol Education Program Adult Treatment Panel III guidelines. LBW (<2·5 kg) and age- and sex-standardized relative leg length (high, medium and low) were the explanatory variables studied. The strength of the associations between the explanatory variables and MetS was estimated by Poisson regression with robust variance. MetS prevalence was 34·2 %; it was more prevalent in men (36·8 %) than in women (32·2 %). In multivariate analysis, LBW was associated (prevalence ratio; 95 % CI) with MetS only in women (1·28; 1·24, 1·45). Shorter leg length was associated with MetS in both men (1·21; 1·09, 1·35 and 1·46; 1·29, 1·65 for low and medium lengths, respectively) and women (1·12; 1·00, 1·25 and 1·40; 1·22, 1·59 for low and medium lengths, respectively). Additional adjustments for age at menarche and BMI at 20 years old did not change the associations. Poor nutritional status as estimated by LBW and lower leg length in childhood was associated with a higher prevalence of MetS, although LBW was a significant factor only among women.

  12. Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study

    International Nuclear Information System (INIS)

    Le Jeune, Florence; Peron, Julie; Grandjean, Didier; Drapier, Sophie; Verin, Marc; Haegelen, Claire; Garin, Etienne; Millet, Bruno

    2010-01-01

    Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD. We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using 18 F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS. The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits. These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role. (orig.)

  13. Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study

    Energy Technology Data Exchange (ETDEWEB)

    Le Jeune, Florence [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France); Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Centre Eugene Marquis, Service Medecine Nucleaire, Rennes (France); Peron, Julie [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Clinique Neurologique, Rennes (France); University of Geneva, Neuroscience of Emotion and Affective Dynamics, Department of Psychology and Swiss Center for Affective Sciences, Geneva (Switzerland); Grandjean, Didier [University of Geneva, Neuroscience of Emotion and Affective Dynamics, Department of Psychology and Swiss Center for Affective Sciences, Geneva (Switzerland); Drapier, Sophie; Verin, Marc [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Clinique Neurologique, Rennes (France); Haegelen, Claire [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Service de Neurochirurgie, Rennes (France); Garin, Etienne [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France); Millet, Bruno [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); S.H.U. Psychiatrie Adulte, CH Guillaume Regnier, Rennes (France)

    2010-08-15

    Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD. We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using {sup 18}F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS. The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits. These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role. (orig.)

  14. Analysis of association of clinical aspects and IL1B tagSNPs with severe preeclampsia.

    Science.gov (United States)

    Leme Galvão, Larissa Paes; Menezes, Filipe Emanuel; Mendonca, Caio; Barreto, Ikaro; Alvim-Pereira, Claudia; Alvim-Pereira, Fabiano; Gurgel, Ricardo

    2016-01-01

    This study investigates the association between IL1B genotypes using a tag SNP (single polymorphism) approach, maternal and environmental factors in Brazilian women with severe preeclampsia. A case-control study with a total of 456 patients (169 preeclamptic women and 287 controls) was conducted in the two reference maternity hospitals of Sergipe state, Northeast Brazil. A questionnaire was administered and DNA was extracted to genotype the population for four tag SNPs of the IL1Beta: rs 1143643, rs 1143633, rs 1143634 and rs 1143630. Haplotype association analysis and p-values were calculated using the THESIAS test. Odds ratio (OR) estimation, confidence interval (CI) and multivariate logistic regression were performed. High pregestational body mass index (pre-BMI), first gestation, cesarean section, more than six medical visits, low level of consciousness on admission and TC and TT genotype in rs1143630 of IL1Beta showed association with the preeclamptic group in univariate analysis. After multivariate logistic regression pre-BMI, first gestation and low level of consciousness on admission remained associated. We identified an association between clinical variables and preeclampsia. Univariate analysis suggested that inflammatory process-related genes, such as IL1B, may be involved and should be targeted in further studies. The identification of the genetic background involved in preeclampsia host response modulation is mandatory in order to understand the preeclampsia process.

  15. Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Cortese, Samuele; Moreira-Maia, Carlos Renato; St Fleur, Diane; Morcillo-Peñalver, Carmen; Rohde, Luis Augusto; Faraone, Stephen V

    2016-01-01

    Impulsivity and inattention related to attention deficit hyperactivity disorder (ADHD) may increase food intake and, consequently, weight gain. However, findings on the association between obesity/overweight and ADHD are mixed. The authors conducted a meta-analysis to estimate this association. A broad range of databases was searched through Aug. 31, 2014. Unpublished studies were also obtained. Study quality was rated with the Newcastle-Ottawa Scale. Random-effects models were used. Forty-two studies that included a total of 728,136 individuals (48,161 ADHD subjects; 679,975 comparison subjects) were retained. A significant association between obesity and ADHD was found for both children (odds ratio=1.20, 95% CI=1.05-1.37) and adults (odds ratio=1.55, 95% CI=1.32-1.81). The pooled prevalence of obesity was increased by about 70% in adults with ADHD (28.2%, 95% CI=22.8-34.4) compared with those without ADHD (16.4%, 95% CI=13.4-19.9), and by about 40% in children with ADHD (10.3%, 95% CI=7.9-13.3) compared with those without ADHD (7.4%, 95% CI=5.4-10.1). The significant association between ADHD and obesity remained when limited to studies 1) reporting odds ratios adjusted for possible confounding factors; 2) diagnosing ADHD by direct interview; and 3) using directly measured height and weight. Gender, study setting, study country, and study quality did not moderate the association between obesity and ADHD. ADHD was also significantly associated with overweight. Individuals medicated for ADHD were not at higher risk of obesity. This study provides meta-analytic evidence for a significant association between ADHD and obesity/overweight. Further research should address possible underlying mechanisms and the long-term effects of ADHD treatments on weight in individuals with both ADHD and obesity.

  16. Exposure to ionizing radiation during dental X-rays is not associated with risk of developing meningioma: a meta-analysis based on seven case-control studies.

    Science.gov (United States)

    Xu, Ping; Luo, Hong; Huang, Guang-Lei; Yin, Xin-Hai; Luo, Si-Yang; Song, Ju-Kun

    2015-01-01

    Many observational studies have found that exposure to dental X-rays is associated with the risk of development of meningioma. However, these findings are inconsistent. We conducted a meta-analysis to assess the relationship between exposure to dental X-rays and the risk of development of meningioma. The PubMed and EMBASE databases were searched to identify eligible studies. Summary odds ratio (OR) estimates and 95% confidence intervals (95% CIs) were used to compute the risk of meningioma development according to heterogeneity. Subgroup and sensitivity analyses were performed to further explore the potential heterogeneity. Finally, publication bias was assessed. Seven case-control studies involving 6,174 patients and 19,459 controls were included in the meta-analysis. Neither exposure to dental X-rays nor performance of full-mouth panorex X-rays was associated with an increased risk of development of meningioma (overall: OR, 0.97; 95% CI, 0.70-1.32; dental X-rays: OR, 1.05; 95% CI, 0.89-1.25; panorex X-rays: OR, 1.01; 95% CI, 0.76-1.34). However, exposure to bitewing X-rays was associated with a slightly increased risk of development of meningioma (OR, 1.73; 95% CI, 1.28-2.34). Similar results were obtained in the subgroup and sensitivity analyses. Little evidence of publication bias was observed. Based on the currently limited data, there is no association between exposure to dental X-rays and the risk of development of meningioma. However, these results should be cautiously interpreted because of the heterogeneity among studies. Additional large, high-quality clinical trials are needed to evaluate the association between exposure to dental X-rays and the risk of development of meningioma.

  17. Stepwise Distributed Open Innovation Contests for Software Development: Acceleration of Genome-Wide Association Analysis.

    Science.gov (United States)

    Hill, Andrew; Loh, Po-Ru; Bharadwaj, Ragu B; Pons, Pascal; Shang, Jingbo; Guinan, Eva; Lakhani, Karim; Kilty, Iain; Jelinsky, Scott A

    2017-05-01

    The association of differing genotypes with disease-related phenotypic traits offers great potential to both help identify new therapeutic targets and support stratification of patients who would gain the greatest benefit from specific drug classes. Development of low-cost genotyping and sequencing has made collecting large-scale genotyping data routine in population and therapeutic intervention studies. In addition, a range of new technologies is being used to capture numerous new and complex phenotypic descriptors. As a result, genotype and phenotype datasets have grown exponentially. Genome-wide association studies associate genotypes and phenotypes using methods such as logistic regression. As existing tools for association analysis limit the efficiency by which value can be extracted from increasing volumes of data, there is a pressing need for new software tools that can accelerate association analyses on large genotype-phenotype datasets. Using open innovation (OI) and contest-based crowdsourcing, the logistic regression analysis in a leading, community-standard genetics software package (PLINK 1.07) was substantially accelerated. OI allowed us to do this in innovation, we achieved an end-to-end speedup of 591-fold for a data set size of 6678 subjects by 645 863 variants, compared to PLINK 1.07's logistic regression. This represents a reduction in run time from 4.8 hours to 29 seconds. Accelerated logistic regression code developed in this project has been incorporated into the PLINK2 project. Using iterative competition-based OI, we have developed a new, faster implementation of logistic regression for genome-wide association studies analysis. We present lessons learned and recommendations on running a successful OI process for bioinformatics. © The Author 2017. Published by Oxford University Press.

  18. Meta-Analysis of the Association between Mir-196a-2 Polymorphism and Cancer Susceptibility

    International Nuclear Information System (INIS)

    Zhang, Huan; Su, Yu-liang; Yu, Herbert; Qian, Bi-yun

    2012-01-01

    MicroRNA plays a vital role in gene expression, and microRNA dysregulation is involved in carcinogenesis. The miR-196a-2 polymorphism rs11614913 is reportedly associated with cancer susceptibility. This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk. A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rs11614913 polymorphism. A significant association was found between rs11614913 polymorphism and cancer risk in four genetic models (CT vs. TT, OR=1.15, 95%CI=1.05–1.27; CC vs. TT, OR=1.23, 95%CI=1.08–1.39; Dominant model, OR=1.17, 95%CI=1.06–1.30; Additive model, OR=1.08, 95%CI=1.01–1.14). In the subgroup analysis of different tumor types, the C allele was associated with increased risk of lung, breast, and colorectal cancer, but not with liver, gastric, or esophageal cancer. In the subgroup analysis by ethnicity, a significantly increased risk of cancer was found among Asians in all genetic models, but no associations were found in the Caucasian subgroup. The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations

  19. THE COMPLEX ANALYSIS METHOD OF SEMANTIC ASSOCIATIONS IN STUDYING THE STUDENTS’ CREATIVE ETHOS

    Directory of Open Access Journals (Sweden)

    P. A. Starikov

    2013-01-01

    Full Text Available The paper demonstrates the sociological research findings concerning the students’ ideas of creativity based on the questionnaires and testing of the students of the natural science, humanities and technical profiles at Siberian Federal University over the period of 2007-2011.The author suggests a new method of semantic association analysis in order to identify the latent groups of notions related to the concept of creativity. The range of students’ common opinions demonstrate the obvious trend for humanizing the idea of creativity, considering  it as the perfect mode of human existence, which coincide with the ideas of K. Rogers, A. Maslow and other scholars. Today’s students associate creativity primarily with pleasure, self-development, self-expression, inspiration, improvisation, spontaneity; and the resulting semantic complex incorporates such characteristics of creative work as goodness, abundance of energy, integrity, health, freedom and independence, self-development and spirituality.The obtained data prove the importance of the inspiration experience in creative pedagogy; the research outcomes along with the continuing monitoring of students attitude to creativity development can optimize the learning process. The author emphasizes the necessity of introducing some special courses, based on the integral approach (including social, philosophical, psychological, psycho-social and technical aspects, and aimed at developing students’ creative competence. 

  20. Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

    OpenAIRE

    Ng, Maggie C. Y.; Shriner, Daniel; Chen, Brian H.; Li, Jiang; Chen, Wei-Min; Guo, Xiuqing; Liu, Jiankang; Bielinski, Suzette J.; Yanek, Lisa R.; Nalls, Michael A.; Comeau, Mary E.; Rasmussen-Torvik, Laura J.; Jensen, Richard A.; Evans, Daniel S.; Sun, Yan V.

    2014-01-01

    Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 case...

  1. Simultaneous analysis of all SNPs in genome-wide and re-sequencing association studies.

    Directory of Open Access Journals (Sweden)

    Clive J Hoggart

    2008-07-01

    Full Text Available Testing one SNP at a time does not fully realise the potential of genome-wide association studies to identify multiple causal variants, which is a plausible scenario for many complex diseases. We show that simultaneous analysis of the entire set of SNPs from a genome-wide study to identify the subset that best predicts disease outcome is now feasible, thanks to developments in stochastic search methods. We used a Bayesian-inspired penalised maximum likelihood approach in which every SNP can be considered for additive, dominant, and recessive contributions to disease risk. Posterior mode estimates were obtained for regression coefficients that were each assigned a prior with a sharp mode at zero. A non-zero coefficient estimate was interpreted as corresponding to a significant SNP. We investigated two prior distributions and show that the normal-exponential-gamma prior leads to improved SNP selection in comparison with single-SNP tests. We also derived an explicit approximation for type-I error that avoids the need to use permutation procedures. As well as genome-wide analyses, our method is well-suited to fine mapping with very dense SNP sets obtained from re-sequencing and/or imputation. It can accommodate quantitative as well as case-control phenotypes, covariate adjustment, and can be extended to search for interactions. Here, we demonstrate the power and empirical type-I error of our approach using simulated case-control data sets of up to 500 K SNPs, a real genome-wide data set of 300 K SNPs, and a sequence-based dataset, each of which can be analysed in a few hours on a desktop workstation.

  2. Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

    NARCIS (Netherlands)

    Sud, A. (Amit); Thomsen, H. (Hauke); Law, P.J. (Philip J.); A. Försti (Asta); Filho, M.I.D.S. (Miguel Inacio Da Silva); Holroyd, A. (Amy); P. Broderick (Peter); Orlando, G. (Giulia); Lenive, O. (Oleg); Wright, L. (Lauren); R. Cooke (Rosie); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); J. Peto (Julian); F. Canzian (Federico); Eeles, R. (Rosalind); Z. Kote-Jarai; K.R. Muir (K.); Pashayan, N. (Nora); B.E. Henderson (Brian); C.A. Haiman (Christopher); S. Benlloch (Sara); F.R. Schumacher (Fredrick R); Olama, A.A.A. (Ali Amin Al); S.I. Berndt (Sonja); G. Conti (Giario); F. Wiklund (Fredrik); S.J. Chanock (Stephen); Stevens, V.L. (Victoria L.); C.M. Tangen (Catherine M.); Batra, J. (Jyotsna); Clements, J. (Judith); H. Grönberg (Henrik); Schleutker, J. (Johanna); D. Albanes (Demetrius); Weinstein, S. (Stephanie); K. Wolk (Kerstin); West, C. (Catharine); Mucci, L. (Lorelei); Cancel-Tassin, G. (Géraldine); Koutros, S. (Stella); Sorensen, K.D. (Karina Dalsgaard); L. Maehle; D. Neal (David); S.P.L. Travis (Simon); Hamilton, R.J. (Robert J.); S.A. Ingles (Sue); B.S. Rosenstein (Barry S.); Lu, Y.-J. (Yong-Jie); Giles, G.G. (Graham G.); A. Kibel (Adam); Vega, A. (Ana); M. Kogevinas (Manolis); Penney, K.L. (Kathryn L.); Park, J.Y. (Jong Y.); Stanford, J.L. (Janet L.); C. Cybulski (Cezary); B.G. Nordestgaard (Børge); Brenner, H. (Hermann); Maier, C. (Christiane); Kim, J. (Jeri); E.M. John (Esther); P.J. Teixeira; Neuhausen, S.L. (Susan L.); De Ruyck, K. (Kim); Razack, A. (Azad); Newcomb, L.F. (Lisa F.); Lessel, D. (Davor); Kaneva, R. (Radka); N. Usmani (Nawaid); F. Claessens; Townsend, P.A. (Paul A.); Dominguez, M.G. (Manuela Gago); Roobol, M.J. (Monique J.); F. Menegaux (Florence); P. Hoffmann (Per); M.M. Nöthen (Markus); K.-H. JöCkel (Karl-Heinz); Strandmann, E.P.V. (Elke Pogge Von); Lightfoot, T. (Tracy); Kane, E. (Eleanor); Roman, E. (Eve); Lake, A. (Annette); Montgomery, D. (Dorothy); Jarrett, R.F. (Ruth F.); A.J. Swerdlow (Anthony ); A. Engert (Andreas); N. Orr (Nick); K. Hemminki (Kari); Houlston, R.S. (Richard S.)

    2017-01-01

    textabstractSeveral susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and

  3. Epstein-Barr virus is associated with periodontal diseases: A meta-analysis based on 21 case-control studies.

    Science.gov (United States)

    Gao, Zilong; Lv, Juan; Wang, Min

    2017-02-01

    Some controversies still exist between the detection of Epstein-Barr virus (EBV)'s DNA and risks of periodontal diseases. Hence, a comprehensive meta-analysis on all available literatures was performed to clarify the relationship between EBV and preidontitis.A comprehensive search was conducted within the PUBMED, EMBASE, and WANFANG databases up to October 10th, 2016 according to inclusion and exclusion criteria and finally 21 case-control literatures were obtained. The outcomes including odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Publication bias was determined by Begg or Egger test. Sensitivity analysis was used to investigate reliability and stability of the results.According to the data from included trials, the association between overall increased risks of periodontitis and the detection of EBV was significant (OR = 6.199, 95% CI = 3.119-12.319, P disease-type analysis, the pooled ORs for chronic periodontitis and aggressive periodontitis were 6.586 (95% CI = 3.042-14.262, P diseases. SgP and tissue are available for detecting EBV in patients of periodontitis. At last, our results suggest that detecting EBV of samples in =5 (6) mm sites of periodontal pockets are more sensitive than in ≤3-mm sites.

  4. Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

    DEFF Research Database (Denmark)

    Mitchell, Jonathan S; Li, Ni; Weinhold, Niels

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a ...

  5. E-cadherin expression phenotypes associated with molecular subtypes in invasive non-lobular breast cancer: evidence from a retrospective study and meta-analysis.

    Science.gov (United States)

    Liu, Jiang-Bo; Feng, Chen-Yi; Deng, Miao; Ge, Dong-Feng; Liu, De-Chun; Mi, Jian-Qiang; Feng, Xiao-Shan

    2017-08-01

    This retrospective study and meta-analysis was designed to explore the relationship between E-cadherin (E-cad) expression and the molecular subtypes of invasive non-lobular breast cancer, especially in early-stage invasive ductal carcinoma (IDC). A total of 156 post-operative cases of early-stage IDCs were retrospectively collected for the immunohistochemistry (IHC) detection of E-cad expression. The association of E-cad expression with molecular subtypes of early-stage IDCs was analyzed. A literature search was conducted in March 2016 to retrieve publications on E-cad expression in association with molecular subtypes of invasive non-lobular breast cancer, and a meta-analysis was performed to estimate the relational statistics. E-cad was expressed in 82.7% (129/156) of early-stage IDCs. E-cad expression was closely associated with the molecular types of early-stage IDCs (P cancer (TNBC) than in other molecular subtypes (TNBC vs. luminal A: RR = 3.45, 95% CI = 2.79-4.26; TNBC vs. luminal B: RR = 2.41, 95% CI = 1.49-3.90; TNBC vs. HER2-enriched: RR = 1.95, 95% CI = 1.24-3.07). Early-stage IDCs or invasive non-lobular breast cancers with the TNBC molecular phenotype have a higher risk for the loss of E-cad expression than do tumors with non-TNBC molecular phenotypes, suggesting that E-cad expression phenotypes were closely related to molecular subtypes and further studies are needed to clarify the underlying mechanism.

  6. Is Child Abuse Associated with Adolescent Obesity? A Population Cohort Study.

    Science.gov (United States)

    Hawton, Katherine; Norris, Tom; Crawley, Esther; Shield, Julian P H

    Child abuse is associated with obesity in adulthood through multiple mechanisms. However, little is known about the relationship between abuse and obesity during adolescence. The aim of this study was to investigate, using a birth cohort, whether there is an association between child abuse and overweight or obesity in adolescence. This study utilizes data from the Avon Longitudinal Study of Parents and Children, a prospective cohort study based in South West England. Using data from the 4205 children with complete data at 13 and 16 years, we analyzed body mass index (BMI) and anonymous parental report of abuse. Abuse was categorized as emotional, physical, or sexual. A sub-sample of 3429 had BMI recorded at 18 years, enabling a longitudinal analysis of BMI trajectories. Using linear and logistic regression analysis, adjusting for sex and family adversity, no association was found between child abuse and BMI, BMI Z-scores, overweight, or obesity, at 13 or 16 years, with all confidence intervals straddling the null. There was weak evidence of a negative association between physical and emotional abuse and BMI trajectories between 13 and 18 years. No relationship was found between child abuse and adolescent obesity in this cohort. This challenges the assumption that adolescent obesity is linked to previous child abuse, as demonstrated for obesity in adult life. A further longitudinal study utilizing both parental and child reports with data record linkage, to improve reporting of abuse, and including neglect as an abuse category, would be desirable.

  7. Biodiversity analysis by polyphasic study of marine bacteria associated with biocorrosion phenomena.

    Science.gov (United States)

    Boudaud, N; Coton, M; Coton, E; Pineau, S; Travert, J; Amiel, C

    2010-07-01

    A polyphasic approach was used to study the biodiversity bacteria associated with biocorrosion processes, in particular sulfate-reducing bacteria (SRB) and thiosulfate-reducing bacteria (TRB) which are described to be particularly aggressive towards metallic materials, notably via hydrogen sulfide release. To study this particular flora, an infrared spectra library of 22 SRB and TRB collection strains were created using a Common Minimum Medium (CMM) developed during this study and standardized culture conditions. The CMM proved its ability to allow for growth of both SRB and TRB strains. These sulfurogen collection strains were clearly discriminated and differentiated at the genus level by fourier transform infrared (FT-IR) spectroscopy. In a second step, infrared spectra of isolates, recovered from biofilms formed on carbon steel coupons immersed for 1 year in three different French harbour areas, were compared to the infrared reference spectra library. In parallel, molecular methods (M13-PCR and 16S rRNA gene sequencing) were used to qualitatively evaluate the intra- and inter-species genetic diversity of biofilm isolates. The biodiversity study indicated that strains belonging to the Vibrio genus were the dominant population; strains belonging to the Desulfovibrio genus (SRB) and Peptostreptococcaceae were also identified. Overall, the combination of the FT-IR spectroscopy and molecular approaches allowed for the taxonomic and ecological study of a bacterial flora, cultivated on CMM, associated with microbiology-induced corrosion (MIC) processes. Via the use of the CMM medium, the culture of marine bacteria (including both SRB and TRB bacteria) was allowed, and the implication of nonsulforogen bacteria in MIC was observed. Their involvement in the biocorrosion phenomena will have to be studied and taken into account in the future. © 2009 The Authors. Journal compilation © 2009 The Society for Applied Microbiology.

  8. Replication of genome wide association studies of alcohol dependence: support for association with variation in ADH1C.

    Directory of Open Access Journals (Sweden)

    Joanna M Biernacka

    Full Text Available Genome-wide association studies (GWAS have revealed many single nucleotide polymorphisms (SNPs associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017. Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI = 0.80 (0.66, 0.95; women: OR (95%CI = 0.83 (0.66, 1.03. We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081, and independently in the alcohol-dependent cases (p = 0.046. Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.

  9. Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

    DEFF Research Database (Denmark)

    Sud, Amit; Thomsen, Hauke; Law, Philip J.

    2017-01-01

    Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 co...

  10. Association between Dietary Patterns and the Indicators of Obesity among Chinese: A Cross-Sectional Study.

    Science.gov (United States)

    Shu, Long; Zheng, Pei-Fen; Zhang, Xiao-Yan; Si, Cai-Juan; Yu, Xiao-Long; Gao, Wei; Zhang, Lun; Liao, Dan

    2015-09-17

    No previous study has investigated dietary pattern in association with obesity risk in a middle-aged Chinese population. The purpose of this study was to evaluate the associations between dietary patterns and the risk of obesity in the city of Hangzhou, the capital of Zhejiang Province, east China. In this cross-sectional study of 2560 subjects aged 45-60 years, dietary intakes were evaluated using a semi-quantitative food frequency questionnaire (FFQ). All anthropometric measurements were obtained using standardized procedures. The partial correlation analysis was performed to assess the associations between dietary patterns and body mass index (BMI), waist circumference (WC), and waist to hip ratio (WHR). Multivariate logistic regression analysis was used to examine the associations between dietary patterns and obesity, with adjustment for potential confounders. Four major dietary patterns were extracted by means of factor analysis: animal food, traditional Chinese, western fast-food, and high-salt patterns. The animal food pattern was positively associated with BMI (r = 0.082, 0.144, respectively, p associated with BMI (r = -0.047, -0.116, respectively, p food pattern scores had a greater odds ratio for abdominal obesity (odds ratio (OR) = 1.67; 95% confidence interval (CI): 1.188-2.340; p obesity (OR = 0.63; 95% CI: 0.441-0.901, p food pattern was associated with a higher risk of abdominal obesity, while the traditional Chinese pattern was associated with a lower risk of abdominal obesity. Further prospective studies are warranted to confirm these findings.

  11. A robust statistical method for association-based eQTL analysis.

    Directory of Open Access Journals (Sweden)

    Ning Jiang

    Full Text Available It has been well established that theoretical kernel for recently surging genome-wide association study (GWAS is statistical inference of linkage disequilibrium (LD between a tested genetic marker and a putative locus affecting a disease trait. However, LD analysis is vulnerable to several confounding factors of which population stratification is the most prominent. Whilst many methods have been proposed to correct for the influence either through predicting the structure parameters or correcting inflation in the test statistic due to the stratification, these may not be feasible or may impose further statistical problems in practical implementation.We propose here a novel statistical method to control spurious LD in GWAS from population structure by incorporating a control marker into testing for significance of genetic association of a polymorphic marker with phenotypic variation of a complex trait. The method avoids the need of structure prediction which may be infeasible or inadequate in practice and accounts properly for a varying effect of population stratification on different regions of the genome under study. Utility and statistical properties of the new method were tested through an intensive computer simulation study and an association-based genome-wide mapping of expression quantitative trait loci in genetically divergent human populations.The analyses show that the new method confers an improved statistical power for detecting genuine genetic association in subpopulations and an effective control of spurious associations stemmed from population structure when compared with other two popularly implemented methods in the literature of GWAS.

  12. Association of Gestational Hypertensive Disorders with Retinopathy of prematurity: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Chan, Priscilla Y L; Tang, Shu-Min; Au, Sunny C L; Rong, Shi-Song; Lau, Henry H W; Ko, Simon T C; Ng, Danny S C; Chen, Li Jia; Yam, Jason C S

    2016-08-05

    The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed.

  13. The association of interleukin-1alpha and interleukin-1beta polymorphisms with the risk of Graves' disease in a case-control study and meta-analysis.

    Science.gov (United States)

    Liu, Nan; Li, Xuejun; Liu, Changqin; Zhao, Yongju; Cui, Bin; Ning, Guang

    2010-04-01

    The proinflammatory cytokine interleukin (IL)-1 family has a central role in mediating inflammation and joint destruction in Graves' disease (GD). A number of studies, investigating rs1800587 (IL-1alpha, T-889 C) and rs16944 (IL-1beta, A-511 G) polymorphisms to test their possible association with GD and Graves' ophthalmopathy (GO), had inconsistent results. Our study aims to further evaluate the possible association of these two polymorphisms with GD and GO within the Han Chinese population using a case-control association study as well as a meta-analysis covering three previous studies from Taiwan, Iran, and Poland. Based on 760 Chinese GD patients, including 190 of GO cases among them, and 735 healthy control subjects, our data showed that the genotype or allele distributions of rs1800587 and rs16944 polymorphisms were significantly associated with GD (p = 0.003-0.049) and more so with GO (p = 0.001-0.021). The meta-analysis showed the risk-increasing effects for the TC and TT genotypes of rs1800587 in GD (odds ratio [OR] = 2.07, p = 0.03) and GO (OR = 3.22, p = 0.04), and a protective effect for the AA genotype of rs16944 in GD (OR = 0.70, p = 0.002) and GO (OR = 0.65, p = 0.02). The results confirmed that the rs1800587 (IL-alpha, T-889 C) and rs16944 (IL-1beta, A-511 G) polymorphisms may confer susceptibility to GD and GO in Asian population.

  14. Association between hyperglycemia and retinopathy of prematurity: a systemic review and meta-analysis

    Science.gov (United States)

    Au, Sunny C. L.; Tang, Shu-Min; Rong, Shi-Song; Chen, Li-Jia; Yam, Jason C. S.

    2015-01-01

    As the role of hyperglycemia in the development of retinopathy of prematurity (ROP) has not been well established, a meta-analysis of the association between hyperglycemia and ROP was conducted. Studies were identified through literature search in MEDLINE and EMBASE up to June 20, 2014 with keywords related to “hyperglycaemia” and “ROP”. Nine eligible studies involving 1939 neonates with 509 cases of ROP were included. Unadjusted analyses showed that hyperglycemia was significantly associated with ROP (Odds ratio [OR] = 4.16, Phyperglycemia (Standardized mean difference [SMD] = 1.21, Phyperglycemia with ROP (adjusted OR 1.08, P = 0.03); and no significant association on mean glucose level with ROP (adjusted OR = 1.08, P = 0.15). Hence, hyperglycemia cannot be definitely considered as a risk factor for ROP, and further studies should adjust for potential confounding factors to clarify this association. PMID:25766465

  15. Factors associated with adolescent cigarette smoking in Greece: Results from a cross sectional study (GYTS Study

    Directory of Open Access Journals (Sweden)

    Gourgoulianis Konstantinos

    2008-09-01

    Full Text Available Abstract Background Data about the predictors of smoking among adolescents in Greece are sparse. We tried to identify factors associated with current cigarette smoking among in-school adolescents in Greece in the context of GYTS study. Methods A secondary analysis of data from a questionnaire study using the Global Youth Tobacco Survey methodology was conducted to identify factors associated with smoking among adolescents in Greece. Data were collected in 2004–2005. The outcome variable was cigarette smoking within the past 30 days preceding the survey while independent variables included age, gender, parental educational status, parental smoking, perception of harmfulness of smoking, and the amount of pocket money at the adolescent's disposal. Results 6141 adolescents (51.5% males and 48.5% females participated in the study. In multivariate analysis, cigarette smoking was associated with male gender (OR: 1.62; 95% CI: 1, 08–3.08, parental smoking (OR: 2.59; 95% CI: 1.45–5.89, and having pocket money ≥ 16 Euros (OR: 2.64; 95% CI: 1.19–5.98. Conclusion Male gender, parental smoking, and having pocket-money ≥ 16 Euros were independently associated with current smoking among Greek students. These findings could be taken into account in order to formulate a comprehensive anti-smoking strategy in Greece.

  16. Carotenoids and risk of fracture: a meta-analysis of observational studies.

    Science.gov (United States)

    Xu, Jiuhong; Song, Chunli; Song, Xiaochao; Zhang, Xi; Li, Xinli

    2017-01-10

    To quantify the association between dietary and circulating carotenoids and fracture risk, a meta-analysis was conducted by searching MEDLINE and EMBASE databases for eligible articles published before May 2016. Five prospective and 2 case-control studies with 140,265 participants and 4,324 cases were identified in our meta-analysis. Among which 5 studies assessed the association between dietary carotenoids levels and hip fracture risk, 2 studies focused on the association between circulating carotenoids levels and any fracture risk. A random-effects model was employed to summarize the risk estimations and their 95% confidence intervals (CIs). Hip fracture risk among participants with high dietary total carotenoids intake was 28% lower than that in participants with low dietary total carotenoids (OR: 0.72; 95% CI: 0.51, 1.01). A similar risk of hip fracture was found for β-carotene based on 5 studies, the summarized OR for high vs. low dietary β-carotene was 0.72 (95% CI: 0.54, 0.95). However, a significant between-study heterogeneity was found (total carotene: I2 = 59.4%, P = 0.06; β-carotene: I2 = 74.4%, P = 0.04). Other individual carotenoids did not show significant associations with hip fracture risk. Circulating carotene levels had no significant association with any fracture risk, the pooled OR (95% CI) was 0.83 (0.59, 1.17). Based on the evidence from observational studies, our meta-analysis supported the hypothesis that higher dietary total carotenoids or β-carotene intake might be potentially associated with a low risk of hip fracture, however, future well-designed prospective cohort studies and randomized controlled trials are warranted to specify the associations between carotenoids and fracture.

  17. A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.

    Science.gov (United States)

    Newman, Anne B; Walter, Stefan; Lunetta, Kathryn L; Garcia, Melissa E; Slagboom, P Eline; Christensen, Kaare; Arnold, Alice M; Aspelund, Thor; Aulchenko, Yurii S; Benjamin, Emelia J; Christiansen, Lene; D'Agostino, Ralph B; Fitzpatrick, Annette L; Franceschini, Nora; Glazer, Nicole L; Gudnason, Vilmundur; Hofman, Albert; Kaplan, Robert; Karasik, David; Kelly-Hayes, Margaret; Kiel, Douglas P; Launer, Lenore J; Marciante, Kristin D; Massaro, Joseph M; Miljkovic, Iva; Nalls, Michael A; Hernandez, Dena; Psaty, Bruce M; Rivadeneira, Fernando; Rotter, Jerome; Seshadri, Sudha; Smith, Albert V; Taylor, Kent D; Tiemeier, Henning; Uh, Hae-Won; Uitterlinden, André G; Vaupel, James W; Walston, Jeremy; Westendorp, Rudi G J; Harris, Tamara B; Lumley, Thomas; van Duijn, Cornelia M; Murabito, Joanne M

    2010-05-01

    Genome-wide association studies (GWAS) may yield insights into longevity. We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x 10(-7) for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage. Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings.

  18. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Matheson, Melanie C; Pers, Tune Hannes

    2013-01-01

    Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up th...

  19. Overrepresentation of glutamate signaling in Alzheimer's disease: network-based pathway enrichment using meta-analysis of genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Eduardo Pérez-Palma

    Full Text Available Genome-wide association studies (GWAS have successfully identified several risk loci for Alzheimer's disease (AD. Nonetheless, these loci do not explain the entire susceptibility of the disease, suggesting that other genetic contributions remain to be identified. Here, we performed a meta-analysis combining data of 4,569 individuals (2,540 cases and 2,029 healthy controls derived from three publicly available GWAS in AD and replicated a broad genomic region (>248,000 bp associated with the disease near the APOE/TOMM40 locus in chromosome 19. To detect minor effect size contributions that could help to explain the remaining genetic risk, we conducted network-based pathway analyses either by extracting gene-wise p-values (GW, defined as the single strongest association signal within a gene, or calculated a more stringent gene-based association p-value using the extended Simes (GATES procedure. Comparison of these strategies revealed that ontological sub-networks (SNs involved in glutamate signaling were significantly overrepresented in AD (p<2.7×10(-11, p<1.9×10(-11; GW and GATES, respectively. Notably, glutamate signaling SNs were also found to be significantly overrepresented (p<5.1×10(-8 in the Alzheimer's disease Neuroimaging Initiative (ADNI study, which was used as a targeted replication sample. Interestingly, components of the glutamate signaling SNs are coordinately expressed in disease-related tissues, which are tightly related to known pathological hallmarks of AD. Our findings suggest that genetic variation within glutamate signaling contributes to the remaining genetic risk of AD and support the notion that functional biological networks should be targeted in future therapies aimed to prevent or treat this devastating neurological disorder.

  20. Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies.

    Directory of Open Access Journals (Sweden)

    Roman Pfister

    2011-10-01

    Full Text Available Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP levels in blood and risk of type 2 diabetes (T2D, but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36% decreased risk of incident T2D per one standard deviation (SD higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97 was similar to that expected (0.96, 0.93-0.98 based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90 and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29 per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies

  1. A Meta-Analysis of Advanced Organizer Studies.

    Science.gov (United States)

    Stone, Carol Leth

    1983-01-01

    Twenty-nine reports yielding 112 studies were analyzed with Glass's meta-analysis technique, and results were compared with predictions from Ausubel's model of assimilative learning. Overall, advance organizers were shown to be associated with increased learning and retention of material to be learned. (Author)

  2. Association between LRP1 C766T polymorphism and Alzheimer's disease susceptibility: a meta-analysis.

    Science.gov (United States)

    Wang, Yun; Liu, Shengyuan; Wang, Jingjing; Zhang, Jie; Hua, Yaqiong; Li, Hua; Tan, Huibiao; Kuai, Bin; Wang, Biao; Sheng, Sitong

    2017-08-16

    Low density lipoprotein receptor-related protein 1 (LRP1) C766T polymorphism (rs1799986) has been extensively investigated for Alzheimer's disease (AD) susceptibility. However, results in different studies have been contradictory. Therefore, we conducted a meta-analysis containing 6455 AD cases and 6304 controls from 26 independent case-control studies to determine whether there was an association between the LRP1 C766T polymorphism and AD susceptibility. The combined analysis showed that there was no significant association between LRP1 C766T polymorphism and AD susceptibility (TT + CT versus CC: OR = 0.920, 95% CI = 0.817-1.037, P = 0.172). In subgroup analysis, significant decreased AD susceptibility was found among Asian population in allele model (T versus C: OR = 0.786, 95% CI = 0.635-0.974, P = 0.028) and dominant model (TT + CT versus CC: OR = 0.800, 95% CI = 0.647-0.990, P = 0.040). Moreover, T allele of LRP1 C766T was statistically associated with late onset of AD (LOAD) (T versus C: OR = 0.858, 95% CI = 0.748-0.985, P = 0.029; TT + CT versus CC: OR = 0.871, 95% CI = 0.763-0.994, P = 0.040). In conclusion, our meta-analysis suggested that LRP1 C766T polymorphism was associated with lower risk of AD in Asian, and could reduce LOAD risk especially. Considering some limitations of our meta-analysis, further large-scale studies should be done to reach a more comprehensive understanding.

  3. Exposure to ionizing radiation during dental X-rays is not associated with risk of developing meningioma: a meta-analysis based on seven case-control studies.

    Directory of Open Access Journals (Sweden)

    Ping Xu

    Full Text Available Many observational studies have found that exposure to dental X-rays is associated with the risk of development of meningioma. However, these findings are inconsistent. We conducted a meta-analysis to assess the relationship between exposure to dental X-rays and the risk of development of meningioma.The PubMed and EMBASE databases were searched to identify eligible studies. Summary odds ratio (OR estimates and 95% confidence intervals (95% CIs were used to compute the risk of meningioma development according to heterogeneity. Subgroup and sensitivity analyses were performed to further explore the potential heterogeneity. Finally, publication bias was assessed.Seven case-control studies involving 6,174 patients and 19,459 controls were included in the meta-analysis. Neither exposure to dental X-rays nor performance of full-mouth panorex X-rays was associated with an increased risk of development of meningioma (overall: OR, 0.97; 95% CI, 0.70-1.32; dental X-rays: OR, 1.05; 95% CI, 0.89-1.25; panorex X-rays: OR, 1.01; 95% CI, 0.76-1.34. However, exposure to bitewing X-rays was associated with a slightly increased risk of development of meningioma (OR, 1.73; 95% CI, 1.28-2.34. Similar results were obtained in the subgroup and sensitivity analyses. Little evidence of publication bias was observed.Based on the currently limited data, there is no association between exposure to dental X-rays and the risk of development of meningioma. However, these results should be cautiously interpreted because of the heterogeneity among studies. Additional large, high-quality clinical trials are needed to evaluate the association between exposure to dental X-rays and the risk of development of meningioma.

  4. Marker-trait association study for protein content in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Jadhav, A A; Rayate, S J; Mhase, L B; Thudi, M; Chitikineni, A; Harer, P N; Jadhav, A S; Varshney, R K; Kulwal, P L

    2015-06-01

    Chickpea (Cicer arietinum L.) is the second most important cool season food legume cultivated in arid and semiarid regions of the world. The objective of the present study was to study variation for protein content in chickpea germplasm, and to find markers associated with it. A set of 187 genotypes comprising both international and exotic collections, and representing both desi and kabuli types with protein content ranging from 13.25% to 26.77% was used. Twenty-three SSR markers representing all eight linkage groups (LG) amplifying 153 loci were used for the analysis. Population structure analysis identified three subpopulations, and corresponding Q values of principal components were used to take care of population structure in the analysis which was performed using general linear and mixed linear models. Marker-trait association (MTA) analysis identified nine significant associations representing four QTLs in the entire population. Subpopulation analyses identified ten significant MTAs representing five QTLs, four of which were common with that of the entire population. Two most significant QTLs linked with markers TR26.205 and CaM1068.195 were present on LG3 and LG5. Gene ontology search identified 29 candidate genes in the region of significant MTAs on LG3. The present study will be helpful in concentrating on LG3 and LG5 for identification of closely linked markers for protein content in chickpea and for their use in molecular breeding programme for nutritional quality improvement.

  5. Effect of perioperative oral care on prevention of postoperative pneumonia associated with esophageal cancer surgery: A multicenter case-control study with propensity score matching analysis.

    Science.gov (United States)

    Soutome, Sakiko; Yanamoto, Souichi; Funahara, Madoka; Hasegawa, Takumi; Komori, Takahide; Yamada, Shin-Ichi; Kurita, Hiroshi; Yamauchi, Chika; Shibuya, Yasuyuki; Kojima, Yuka; Nakahara, Hirokazu; Oho, Takahiko; Umeda, Masahiro

    2017-08-01

    The aim of this study was to investigate the effectiveness of oral care in prevention of postoperative pneumonia associated with esophageal cancer surgery.Postoperative pneumonia is a severe adverse event associated with esophageal cancer surgery. It is thought to be caused by aspiration of oropharyngeal fluid containing pathogens. However, the relationship between oral health status and postoperative pneumonia has not been well investigated.This study included 539 patients with esophageal cancer undergoing surgery at 1 of 7 university hospitals. While 306 patients received perioperative oral care, 233 did not. Various clinical factors as well as occurrence of postoperative pneumonia were retrospectively evaluated. Propensity-score matching was performed to minimize selection biases associated with comparison of retrospective data between the oral care and control groups. Factors related to postoperative pneumonia were analyzed by logistic regression analysis.Of the original 539 patients, 103 (19.1%) experienced postoperative pneumonia. The results of multivariate analysis of the 420 propensity score-matched patients revealed longer operation time, postoperative dysphagia, and lack of oral care intervention to be significantly correlated with postoperative pneumonia.The present findings demonstrate that perioperative oral care can reduce the risk of postoperative pneumonia in patients undergoing esophageal cancer surgery.

  6. Genome-wide association study of rust traits in orchardgrass using SLAF-seq technology.

    Science.gov (United States)

    Zeng, Bing; Yan, Haidong; Liu, Xinchun; Zang, Wenjing; Zhang, Ailing; Zhou, Sifan; Huang, Linkai; Liu, Jinping

    2017-01-01

    While orchardgrass ( Dactylis glomerata L.) is a well-known perennial forage species, rust diseases cause serious reductions in the yield and quality of orchardgrass; however, genetic mechanisms of rust resistance are not well understood in orchardgrass. In this study, a genome-wide association study (GWAS) was performed using specific-locus amplified fragment sequencing (SLAF-seq) technology in orchardgrass. A total of 2,334,889 SLAF tags were generated to produce 2,309,777 SNPs. ADMIXTURE analysis revealed unstructured subpopulations for 33 accessions, indicating that this orchardgrass population could be used for association analysis. Linkage disequilibrium (LD) analysis revealed an average r 2 of 0.4 across all SNP pairs, indicating a high extent of LD in these samples. Through GWAS, a total of 4,604 SNPs were found to be significantly ( P  rust trait. The bulk analysis discovered a number of 5,211 SNPs related to rust trait. Two candidate genes, including cytochrome P450, and prolamin were implicated in disease resistance through prediction of functional genes surrounding each high-quality SNP ( P  rust traits based on GWAS analysis and bulk analysis. The large number of SNPs associated with rust traits and these two candidate genes may provide the basis for further research on rust resistance mechanisms and marker-assisted selection (MAS) for rust-resistant lineages.

  7. Prioritization of epilepsy associated candidate genes by convergent analysis.

    Science.gov (United States)

    Jia, Peilin; Ewers, Jeffrey M; Zhao, Zhongming

    2011-02-24

    Epilepsy is a severe neurological disorder affecting a large number of individuals, yet the underlying genetic risk factors for epilepsy remain unclear. Recent studies have revealed several recurrent copy number variations (CNVs) that are more likely to be associated with epilepsy. The responsible gene(s) within these regions have yet to be definitively linked to the disorder, and the implications of their interactions are not fully understood. Identification of these genes may contribute to a better pathological understanding of epilepsy, and serve to implicate novel therapeutic targets for further research. In this study, we examined genes within heterozygous deletion regions identified in a recent large-scale study, encompassing a diverse spectrum of epileptic syndromes. By integrating additional protein-protein interaction data, we constructed subnetworks for these CNV-region genes and also those previously studied for epilepsy. We observed 20 genes common to both networks, primarily concentrated within a small molecular network populated by GABA receptor, BDNF/MAPK signaling, and estrogen receptor genes. From among the hundreds of genes in the initial networks, these were designated by convergent evidence for their likely association with epilepsy. Importantly, the identified molecular network was found to contain complex interrelationships, providing further insight into epilepsy's underlying pathology. We further performed pathway enrichment and crosstalk analysis and revealed a functional map which indicates the significant enrichment of closely related neurological, immune, and kinase regulatory pathways. The convergent framework we proposed here provides a unique and powerful approach to screening and identifying promising disease genes out of typically hundreds to thousands of genes in disease-related CNV-regions. Our network and pathway analysis provides important implications for the underlying molecular mechanisms for epilepsy. The strategy can be

  8. Prioritization of epilepsy associated candidate genes by convergent analysis.

    Directory of Open Access Journals (Sweden)

    Peilin Jia

    2011-02-01

    Full Text Available Epilepsy is a severe neurological disorder affecting a large number of individuals, yet the underlying genetic risk factors for epilepsy remain unclear. Recent studies have revealed several recurrent copy number variations (CNVs that are more likely to be associated with epilepsy. The responsible gene(s within these regions have yet to be definitively linked to the disorder, and the implications of their interactions are not fully understood. Identification of these genes may contribute to a better pathological understanding of epilepsy, and serve to implicate novel therapeutic targets for further research.In this study, we examined genes within heterozygous deletion regions identified in a recent large-scale study, encompassing a diverse spectrum of epileptic syndromes. By integrating additional protein-protein interaction data, we constructed subnetworks for these CNV-region genes and also those previously studied for epilepsy. We observed 20 genes common to both networks, primarily concentrated within a small molecular network populated by GABA receptor, BDNF/MAPK signaling, and estrogen receptor genes. From among the hundreds of genes in the initial networks, these were designated by convergent evidence for their likely association with epilepsy. Importantly, the identified molecular network was found to contain complex interrelationships, providing further insight into epilepsy's underlying pathology. We further performed pathway enrichment and crosstalk analysis and revealed a functional map which indicates the significant enrichment of closely related neurological, immune, and kinase regulatory pathways.The convergent framework we proposed here provides a unique and powerful approach to screening and identifying promising disease genes out of typically hundreds to thousands of genes in disease-related CNV-regions. Our network and pathway analysis provides important implications for the underlying molecular mechanisms for epilepsy. The

  9. The association between dietary zinc intake and risk of pancreatic cancer: a meta-analysis.

    Science.gov (United States)

    Li, Li; Gai, Xuesong

    2017-06-30

    Previous reports have suggested a potential association on dietary zinc intake with the risk of pancreatic cancer. Since the associations between different studies were controversial, we therefore conducted a meta-analysis to reassess the relationship between dietary zinc intake and pancreatic cancer risk. A comprehensive search from the databases of PubMed, Embase, Web of Science, and Medline was performed until January 31, 2017. Relative risk (RR) with 95% confidence intervals (CI) derived by using random effect model was used. Sensitivity analysis and publication bias were conducted. Our meta-analysis was based on seven studies involving 1659 cases, including two prospective cohort studies and five case-control studies. The total RR of pancreatic cancer risk for the highest versus the lowest categories of dietary zinc intake was 0.798 (0.621-0.984), with its significant heterogeneity among studies ( I 2 =58.2%, P =0.026). The average Newcastle-Ottawa scale (NOS) score was 7.29, suggesting a high quality. There was no publication bias in the meta-analysis about dietary zinc intake on the risk of pancreatic cancer. Subgroup analyses showed that dietary zinc intake could reduce the risk of pancreatic cancer in case-control studies and among American populations. In conclusion, we found that highest category of dietary zinc intake can significantly reduce the risk of pancreatic cancer, especially among American populations. © 2017 The Author(s).

  10. A positive association between anxiety disorders and cannabis use or cannabis use disorders in the general population- a meta-analysis of 31 studies

    Science.gov (United States)

    2014-01-01

    Background The aim of the current study was to investigate the association between anxiety and cannabis use/cannabis use disorders in the general population. Methods A total of N = 267 studies were identified from a systematic literature search (any time- March 2013) of Medline and PsycInfo databases, and a hand search. The results of 31 studies (with prospective cohort or cross-sectional designs using non-institutionalised cases) were analysed using a random-effects meta-analysis with the inverse variance weights. Lifetime or past 12-month cannabis use, anxiety symptoms, and cannabis use disorders (CUD; dependence and/or abuse/harmful use) were classified according to DSM/ICD criteria or scores on standardised scales. Results There was a small positive association between anxiety and either cannabis use (OR = 1.24, 95% CI: 1.06-1.45, p = .006; N = 15 studies) or CUD (OR = 1.68, 95% CI: 1.23-2.31, p = .001; N = 13 studies), and between comorbid anxiety + depression and cannabis use (OR = 1.68, 95% CI: 1.17-2.40, p = .004; N = 5 studies). The positive associations between anxiety and cannabis use (or CUD) were present in subgroups of studies with ORs adjusted for possible confounders (substance use, psychiatric illness, demographics) and in studies with clinical diagnoses of anxiety. Cannabis use at baseline was significantly associated with anxiety at follow-up in N = 5 studies adjusted for confounders (OR = 1.28, 95% CI: 1.06-1.54, p = .01). The opposite relationship was investigated in only one study. There was little evidence for publication bias. Conclusion Anxiety is positively associated with cannabis use or CUD in cohorts drawn from some 112,000 non-institutionalised members of the general population of 10 countries. PMID:24884989

  11. Association of Interleukin-1 gene clusters polymorphisms with primary open-angle glaucoma: a meta-analysis.

    Science.gov (United States)

    Li, Junhua; Feng, Yifan; Sung, Mi Sun; Lee, Tae Hee; Park, Sang Woo

    2017-11-28

    Previous studies have associated the Interleukin-1 (IL-1) gene clusters polymorphisms with the risk of primary open-angle glaucoma (POAG). However, the results were not consistent. Here, we performed a meta-analysis to evaluate the role of IL-1 gene clusters polymorphisms in POAG susceptibility. PubMed, EMBASE and Cochrane Library (up to July 15, 2017) were searched by two independent investigators. All case-control studies investigating the association between single-nucleotide polymorphisms (SNPs) of IL-1 gene clusters and POAG risk were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for quantifying the strength of association that has been involved in at least two studies. Five studies on IL-1β rs16944 (c. -511C > T) (1053 cases and 986 controls), 4 studies on IL-1α rs1800587 (c. -889C > T) (822 cases and 714 controls), and 4 studies on IL-1β rs1143634 (c. +3953C > T) (798 cases and 730 controls) were included. The results suggest that all three SNPs were not associated with POAG risk. Stratification analyses indicated that the rs1143634 has a suggestive associated with high tension glaucoma (HTG) under dominant (P = 0.03), heterozygote (P = 0.04) and allelic models (P = 0.02), however, the weak association was nullified after Bonferroni adjustments for multiple tests. Based on current meta-analysis, we indicated that there is lack of association between the three SNPs of IL-1 and POAG. However, this conclusion should be interpreted with caution and further well designed studies with large sample-size are required to validate the conclusion as low statistical powers.

  12. Connecting the dots, genome-wide association studies in substance use

    NARCIS (Netherlands)

    Nivard, M.G.; Verweij, K.J.H.; Minica, C.C.; Treur, J.L.; Vink, J.M.; Boomsma, D.I.

    2016-01-01

    The recent genome-wide association (GWA) meta-analysis of lifetime cannabis use by the International Cannabis Consortium marks a milestone in the study of the genetics of cannabis use. Similar milestones for the genetics of substance use were the GWA meta-analyses of four smoking related traits, of

  13. Association of vitamin C with the risk of age-related cataract: a meta-analysis.

    Science.gov (United States)

    Wei, Lin; Liang, Ge; Cai, Chunmei; Lv, Jin

    2016-05-01

    Whether vitamin C is a protective factor for age-related cataract remains unclear. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of vitamin C and the risk of age-related cataract. Pertinent studies were identified by searching in PubMed and in Webscience. The random effect model was used to combine the results. Meta-regression and subgroups analyses were used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Egger's regression asymmetry test. Finally, 15 articles with 20 studies for vitamin C intake and eight articles with 10 studies for serum ascorbate were included in this meta-analysis. The relative risk (RR) and 95% confidence interval of cataract for the highest versus the lowest category of vitamin C intake was 0.814 (0.707-0.938), and the associations were significant in America and Asia. Significant association of cataract risk with highest versus the lowest category of serum ascorbate was found in general [0.704 (0.564-0.879)]. Inverse associations were also found between serum ascorbate and nuclear cataract and posterior subcapsular cataract. Higher vitamin C intake and serum ascorbate might be inversely associated with risk of cataract. Vitamin C intake should be advocated for the primary prevention of cataract. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  14. Kernel machine SNP set analysis provides new insight into the association between obesity and polymorphisms located on the chromosomal 16q.12.2 region: Tehran Lipid and Glucose Study.

    Science.gov (United States)

    Javanrouh, Niloufar; Daneshpour, Maryam S; Soltanian, Ali Reza; Tapak, Leili

    2018-06-05

    Obesity is a serious health problem that leads to low quality of life and early mortality. To the purpose of prevention and gene therapy for such a worldwide disease, genome wide association study is a powerful tool for finding SNPs associated with increased risk of obesity. To conduct an association analysis, kernel machine regression is a generalized regression method, has an advantage of considering the epistasis effects as well as the correlation between individuals due to unknown factors. In this study, information of the people who participated in Tehran cardio-metabolic genetic study was used. They were genotyped for the chromosomal region, evaluation 986 variations located at 16q12.2; build 38hg. Kernel machine regression and single SNP analysis were used to assess the association between obesity and SNPs genotyped data. We found that associated SNP sets with obesity, were almost in the FTO (P = 0.01), AIKTIP (P = 0.02) and MMP2 (P = 0.02) genes. Moreover, two SNPs, i.e., rs10521296 and rs11647470, showed significant association with obesity using kernel regression (P = 0.02). In conclusion, significant sets were randomly distributed throughout the region with more density around the FTO, AIKTIP and MMP2 genes. Furthermore, two intergenic SNPs showed significant association after using kernel machine regression. Therefore, more studies have to be conducted to assess their functionality or precise mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. A bias-reducing pathway enrichment analysis of genome-wide association data confirmed association of the MHC region with schizophrenia.

    LENUS (Irish Health Repository)

    Jia, Peilin

    2012-02-01

    After the recent successes of genome-wide association studies (GWAS), one key challenge is to identify genetic variants that might have a significant joint effect on complex diseases but have failed to be identified individually due to weak to moderate marginal effect. One popular and effective approach is gene set based analysis, which investigates the joint effect of multiple functionally related genes (eg, pathways). However, a typical gene set analysis method is biased towards long genes, a problem that is especially severe in psychiatric diseases.

  16. Serum calcium and incident diabetes: an observational study and meta-analysis.

    Science.gov (United States)

    Sing, C W; Cheng, V K F; Ho, D K C; Kung, A W C; Cheung, B M Y; Wong, I C K; Tan, K C B; Salas-Salvadó, J; Becerra-Tomas, N; Cheung, C L

    2016-05-01

    The study aimed to prospectively evaluate if serum calcium is related to diabetes incidence in Hong Kong Chinese. The results showed that serum calcium has a significant association with increased risk of diabetes. The result of meta-analysis reinforced our findings. This study aimed to evaluate the association of serum calcium, including serum total calcium and albumin-corrected calcium, with incident diabetes in Hong Kong Chinese. We conducted a retrospective cohort study in 6096 participants aged 20 or above and free of diabetes at baseline. Serum calcium was measured at baseline. Incident diabetes was determined from several electronic databases. We also searched relevant databases for studies on serum calcium and incident diabetes and conducted a meta-analysis using fixed-effect modeling. During 59,130.9 person-years of follow-up, 631 participants developed diabetes. Serum total calcium and albumin-corrected calcium were associated with incident diabetes in the unadjusted model. After adjusting for demographic and clinical variables, the association remained significant only for serum total calcium (hazard ratio (HR), 1.32 (95 % confidence interval (CI), 1.02-1.70), highest vs. lowest quartile). In a meta-analysis of four studies including the current study, both serum total calcium (pooled risk ratio (RR), 1.38 (95 % CI, 1.15-1.65); I (2) = 5 %, comparing extreme quantiles) and albumin-corrected calcium (pooled RR, 1.29 (95 % CI, 1.03-1.61); I (2) = 0 %, comparing extreme quantiles) were associated with incident diabetes. Penalized regression splines showed that the association of incident diabetes with serum total calcium and albumin-correlated calcium was non-linear and linear, respectively. Elevated serum calcium concentration is associated with incident diabetes. The mechanism underlying this association warrants further investigation.

  17. Association between race/skin color and premature birth: a systematic review with meta-analysis.

    Science.gov (United States)

    Oliveira, Kelly Albuquerque de; Araújo, Edna Maria de; Oliveira, Keyte Albuquerque de; Casotti, Cesar Augusto; Silva, Carlos Alberto Lima da; Santos, Djanilson Barbosa Dos

    2018-04-09

    To analyze the association between race/skin color and the occurrence of prematurity. Meta-analysis with observational studies, selected by a systematic review in the bibliographic databases Medline and Biblioteca Virtual da Saúde with the descriptors: "Race or ethnic group" and "ethnicity and health" associated with the words "infant premature" and "obstetric labor premature". Articles published in the period from 2010 to 2014, of the observational epidemiological type, in Portuguese, English and Spanish, were included. Articles that did not have abstracts or that were review articles, theses, dissertations, and editorials were excluded. We adopted the relative risk and their respective confidence intervals (95%CI) as measures of effect, obtained through the random effect model and represented by the forest plot type graph. The Egger test and the Newcastle-Ottawa scale, respectively, were used to analyze possible publication biases and the quality of the studies. Of the 926 articles identified, 17 were eligible for the study. Of the 17 full texts published, seven were retrospective cohort studies, nine were cross-sectional studies, and one was a case-control study. Except for one study, the others reported a positive association between race/color of skin and prematurity. Compared with full-term newborns, the relative risk of the combined effect in those born preterm was 1.51 (95%CI 1.39-1.69). The funnel chart suggested publication bias. The present meta-analysis indicated a positive association for the risk of prematurity according to race/skin color.

  18. Multi-element analysis of emeralds and associated rocks by k0 neutron activation analysis

    International Nuclear Information System (INIS)

    Acharya, R.N.; Mondal, R.K.; Burte, P.P.; Nair, A.G.C.; Reddy, N.B.Y.; Reddy, L.K.; Reddy, A.V.R.; Manohar, S.B.

    2000-01-01

    Multi-element analysis was carried out in natural emeralds, their associated rocks and one sample of beryl obtained from Rajasthan, India. The concentrations of 21 elements were assayed by Instrumental Neutron Activation Analysis using the k 0 method (k 0 INAA method) and high-resolution gamma ray spectrometry. The data reveal the segregation of some elements from associated (trapped and host) rocks to the mineral beryl forming the gemstones. A reference rock standard of the US Geological Survey (USGS BCR-1) was also analysed as a control of the method

  19. The association between prostatitis and prostate cancer. Systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Gianpaolo Perletti

    2017-12-01

    Full Text Available Objective: The main outcome of this review was the association between a history of clinical chronic prostatitis (NIH category II or III and a histologically confirmed diagnosis of prostate cancer. Materials and methods: Crude odds ratios and 95% confidence intervals (CI were calculated to analyze dichotomous data. For analysis of pooled data we adopted a random-effects model and the inverse variance weighing method. Heterogeneity was assessed by calculating the I2 value. Results: Out of 2794 screened records, we retrieved 16 full-text articles written in English, reporting the data of 15 case-control studies, involving 422.943 patients. Pooled analysis resulted in a significant crude odds ratio of 1.83 (95% CI: 1.43 to 2.35; P < 0.00001. The total set of data showed considerable heterogeneity (I2 = 91%. Both the Egger’s test and the Begg's test for funnel plot asymmetry did not reach statistical significance. The ‘trim and fill’ method applied to the funnel plot imputed 3 missing studies and the resulting adjusted estimate of the odds ratio was 2.12 (95% CI: 1.38 to 3.22. According to GRADE criteria, the overall quality of the meta-analysis data is low, mainly due to the presence of bias, confounders and extreme effect size outliers. Five among the included studies reported data assessed in 8015 African-American subjects. Pooled analysis resulted in a non-significant crude odds ratio of 1.59 (95% CI: 0.71 to 3.57; P = 0.26, and considerable heterogeneity (I2 = 90%. Conclusions: Meta-analysis of 15 case-control studies shows that a history of clinical chronic prostatitis can significantly increase the odds for prostate cancer in the general population, whereas such association in African-American individuals remains uncertain.

  20. Associations between postprandial insulin and blood glucose responses, appetite sensations and energy intake in normal weight and overweight individuals: a meta-analysis of test meal studies

    DEFF Research Database (Denmark)

    Flint, Anne; Gregersen, Nikolaj T.; Gluud, Lise L.

    2007-01-01

    is unclear whether postprandial blood glucose or insulin exerts a regulatory function in short-term appetite regulation in humans. The aim of this study was to investigate, by use of meta-analysis, the role of blood glucose and insulin in short-term appetite sensation and energy intake (EI......) in normal weight and overweight participants. Data from seven test meal studies were used, including 136 healthy participants (ALL) (92 normal weight (NW) and 44 overweight or obese (OW)). All meals were served as breakfasts after an overnight fast, and appetite sensations and blood samples were obtained...... frequently in the postprandial period. Finally, an ad libitum lunch was served. Data were analysed by fixed effects study level (SL) meta-regression analysis and individual participant data (IPD) regression analysis, using STATA software. In SL analysis, postprandial insulin response was associated...

  1. An updated meta-analysis on the association of MDM2 SNP309 polymorphism with colorectal cancer risk.

    Directory of Open Access Journals (Sweden)

    Xue Qin

    Full Text Available The mouse double minute 2 (MDM2 gene encodes a phosphoprotein that interacts with P53 and negatively regulates its activity. The SNP309 polymorphism (T-G in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and colorectal cancer (CRC risk reported conflicting results. We performed a meta-analysis of all available studies to explore the association of this polymorphism with CRC risk.All studies published up to July 2013 on the association between MDM2 SNP309 polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature database (CBM databases. The association between the MDM2 SNP309 polymorphism and CRC risk was assessed by odds ratios (ORs together with their 95% confidence intervals (CIs.A total of 14 case-control studies including 4460 CRC cases and 4828 controls were identified. We did not find a significant association between the MDM2 SNP309 polymorphism and CRC risk in all genetic models in overall population. However, in subgroup analysis by ethnicity, significant associations were found in Asians (TG vs. TT: OR = 1.197, 95% CI = 1.055-1.358, P=0.005; GG+TG vs. TT: OR = 1.246, 95% CI = 1.106-1.404, P=0.000 and Africans. When stratified by HWE in controls, significantly increased risk was also found among the studies consistent with HWE (TG vs. TT: OR = 1.166, 95% CI = 1.037-1.311, P= 0.010. In subgroup analysis according to p53 mutation status, and gender, no any significant association was detected.The present meta-analysis suggests that the MDM2 is a candidate gene for CRC susceptibility. The MDM2 SNP309 polymorphism may be a risk factor for CRC in Asians.

  2. Identification of TNIP1 Polymorphisms by High Resolution Melting Analysis with Unlabelled Probe: Association with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2012-01-01

    Full Text Available Background. TNFα-induced protein 3 (TNFAIP3 interacting with protein 1 (TNIP1 acts as a negative regulator of NF-κB and plays an important role in maintaining the homeostasis of immune system. A recent genome-wide association study (GWAS showed that the polymorphism of TNIP1 was associated with the disease risk of SLE in Caucasian. In this study, we investigated whether the association of TNIP1 with SLE was replicated in Chinese population. Methods. The association of TNIP1 SNP rs7708392 (G/C was determined by high resolution melting (HRM analysis with unlabeled probe in 285 SLE patients and 336 healthy controls. Results. A new SNP rs79937737 located on 5 bp upstream of rs7708392 was discovered during the HRM analysis. No association of rs7708392 or rs79937737 with the disease risk of SLE was found. Furthermore, rs7708392 and rs79937737 were in weak linkage disequilibrium (LD. Hypotypes analysis of the two SNPs also showed no association with SLE in Chinese population. Conclusions. High resolution melting analysis with unlabeled probes proves to be a powerful and efficient genotyping method for identifying and screening SNPs. No association of rs7708392 or rs79937737 with the disease risk of SLE was observed in Chinese population.

  3. Flavonoids intake and risk of prostate cancer: a meta-analysis of observational studies.

    Science.gov (United States)

    Guo, K; Liang, Z; Liu, L; Li, F; Wang, H

    2016-12-01

    The aim of the study was to assess the association between total flavonoids/flavonoid subclasses intake and prostate cancer risk. Several databases were searched to select eligible studies with predefined criteria. Risk ratios (RRs) with 95% confidence intervals (CIs) were used as the effect size. Publication bias and sensitivity analysis were performed. A total of five studies including four prospective cohort studies and one case-control study were included in the meta-analysis. The pooled result demonstrated a significantly increased risk of prostate cancer with higher intake of total flavonoids (RR = 1.12, 95% CI: 1.02-1.23, P = 0.013). However, sensitivity analysis indicated that there lacked a significant association after removing the study of Wang et al. (RR = 1.17, 95% CI: 0.94-1.46). Subgroup analysis stratified by flavonoids subclasses found that higher intake of anthocyanidins and flavan-3-ols were significantly associated with increased prostate cancer risk (RR = 1.12, 95% CI: 1.03-1.21, P = 0.011; RR = 1.21, 95% CI: 1.10-1.32, P flavonoids may not be associated with prostate cancer risk. © 2016 Blackwell Verlag GmbH.

  4. Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

    International Nuclear Information System (INIS)

    Niu, Nifang; Cunningham, Julie M; Li, Liang; Sun, Zhifu; Yang, Ping; Wang, Liewei; Schaid, Daniel J; Abo, Ryan P; Kalari, Krishna; Fridley, Brooke L; Feng, Qiping; Jenkins, Gregory; Batzler, Anthony; Brisbin, Abra G

    2012-01-01

    Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs) that might contribute to taxane response, we performed a genome-wide association study (GWAS) for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs), followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC) patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196) and NSCLC (A549) cell lines. 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values <10 -4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value < 0.05) associated with either SCLC or NSCLC patient overall survival. Knockdown of PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667), significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA) hsa-miR-584 or hsa-miR-1468. GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel

  5. Long-Term Coffee Consumption Is Associated with Decreased Incidence of New-Onset Hypertension: A Dose-Response Meta-Analysis.

    Science.gov (United States)

    Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Bes-Rastrollo, Maira; Galvano, Fabio; Martinez-Gonzalez, Miguel A

    2017-08-17

    To perform a dose-response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose-response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose-response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.

  6. Long-Term Coffee Consumption Is Associated with Decreased Incidence of New-Onset Hypertension: A Dose–Response Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Giuseppe Grosso

    2017-08-01

    Full Text Available Objective: To perform a dose–response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. Methods: An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose–response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Results: Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose–response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Conclusions: Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.

  7. Sedentary behavior and incident cancer: a meta-analysis of prospective studies.

    Directory of Open Access Journals (Sweden)

    Dong Shen

    Full Text Available Sedentary behavior is ubiquitous in modern adults' daily lives and it has been suggested to be associated with incident cancer. However, the results have been inconsistent. In this study, we performed a systematic review and meta-analysis of prospective cohort studies to clarify the association between sedentary behavior and incident cancer.PubMed and Embase databases were searched up to March 2014. All prospective cohort studies on the association between sedentary behavior and incident cancer were included. The summary relative risks (RRs with 95% confidence intervals (CIs were estimated using random effect model.A total of 17 prospective studies from 14 articles, including a total of 857,581 participants and 18,553 cases, were included in the analysis for sedentary behavior and risk of incident cancer. The overall meta-analysis suggested that sedentary behavior increased risk of cancer (RR = 1.20, 95%CI = 1.12-1.28, with no evidence of heterogeneity between studies (I(2 = 7.3%, P = 0.368. Subgroup analyses demonstrated that there were statistical associations between sedentary behavior and some cancer types (endometrial cancer: RR = 1.28, 95% CI = 1.08-1.53; colorectal cancer: RR = 1.30, 95%CI = 1.12-1.49; breast cancer: RR = 1.17, 95%CI = 1.03-1.33; lung cancer: RR = 1.27, 95%CI = 1.06-1.52. However, there was no association of sedentary behavior with ovarian cancer (RR = 1.26, 95%CI = 0.87-1.82, renal cell carcinoma (RR = 1.11, 95%CI = 0.87-1.41 or non-Hodgkin lymphoid neoplasms (RR = 1.09, 95%CI = 0.82-1.43.The present meta-analysis suggested that prolonged sedentary behavior was independently associated with an increased risk of incident endometrial, colorectal, breast, and lung cancers, but not with ovarian cancer, renal cell carcinoma or non-Hodgkin lymphoid neoplasms.

  8. Association between Habitual Dietary Salt Intake and Risk of Gastric Cancer: A Systematic Review of Observational Studies

    Directory of Open Access Journals (Sweden)

    Sheng Ge

    2012-01-01

    Full Text Available Purpose. Systematic reviews of case-control and prospective studies showed a positive association between habitual salt intake and gastric cancer. Given new studies published thereafter, we carried out a meta-analysis to assess the association between dietary salt intake and gastric cancer. Methods. Case-control studies and cohort studies published between January 1992 and January 2012 on PubMed and Embase were searched. We quantified associations between salt intake and gastric cancer with meta-analysis. Results. Eleven studies (7 case controls and 4 cohorts finally were included in the meta-analysis (total population: n=2076498; events: n=12039. The combined odds ratio showed significantly positive association between high salt intake and gastric cancer compared with low salt intake (OR = 2.05, 95% CI [1.60, 2.62]; P<0.00001. In subgroup meta-analysis, findings were slightly different when analyses were restricted to salty food intake (OR = 2.41, 95% CI [2.08, 2.78]; P<0.00001 as well as in Asia (OR = 1.27 95% CI [1.22, 1.32]; P<0.00001. There was no evidence that sample size, exposure assessment substantially influenced the estimate of effects. Conclusions. The systemic review supports the hypothesis that dietary salt intake is positively associated with the risk of gastric cancer.

  9. Association Rule Analysis for Tour Route Recommendation and Application to Wctsnop

    Science.gov (United States)

    Fang, H.; Chen, C.; Lin, J.; Liu, X.; Fang, D.

    2017-09-01

    The increasing E-tourism systems provide intelligent tour recommendation for tourists. In this sense, recommender system can make personalized suggestions and provide satisfied information associated with their tour cycle. Data mining is a proper tool that extracting potential information from large database for making strategic decisions. In the study, association rule analysis based on FP-growth algorithm is applied to find the association relationship among scenic spots in different cities as tour route recommendation. In order to figure out valuable rules, Kulczynski interestingness measure is adopted and imbalance ratio is computed. The proposed scheme was evaluated on Wangluzhe cultural tourism service network operation platform (WCTSNOP), where it could verify that it is able to quick recommend tour route and to rapidly enhance the recommendation quality.

  10. The association between physical activity and atrial fibrillation applying the Heaviside function in survival analysis: the Multi-Ethnic Study of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Yaser Mokhayeri

    2017-06-01

    Full Text Available OBJECTIVES Although the effect of physical activity (PA on the incidence of atrial fibrillation (AF has been studied, contradictory results have been reported. Such discrepancies may reflect the different effects of various types of PA upon AF, as well as gender interactions. Therefore, we aimed to evaluate the associations of PA types (total, moderate/vigorous, and intentional, as well as walking pace, with AF risk in men and women. METHODS Using the Multi-Ethnic Study of Atherosclerosis Typical Week Physical Activity Survey, 3 PA measures and walking pace were calculated among 6,487 men and women aged 45-84 years. The incidence of AF over approximately 11 years of follow-up was ascertained. The association of each PA measure and walking pace with AF incidence was estimated using multivariable Cox proportional hazard models. An extended Cox model with Heaviside functions (hv of time was used to estimate the effects of time-varying covariates. RESULTS During 11 years of follow-up (49,557 person-years, 242 new AF cases occurred. The incidence rate of AF was 48.83 per 10,000 person-years. The proportional hazard (PH assumption for total PA among women was not met; hence, we used the hv to calculate the hazard ratio. Total PA in women in the hv2 analysis was negatively associated with AF in all 3 models, although for hv1 no significant association was observed. The PH assumption for walking pace among men was not met, and none of the hv showed a statistically significant association between walking pace and AF in men. CONCLUSIONS These results suggest that PA is inversely associated with AF in women.

  11. Family based association analysis of the IL2 and IL15 genes in allergic disorders

    DEFF Research Database (Denmark)

    Christensen, Ulla; Haagerup, Annette; Binderup, Helle

    2006-01-01

    ) identified in a family based association study of two Danish samples comprising a total of 235 families with allergic diseases. None of the IL15 SNPs showed significant association and the haplotype analysis yielded inconsistent results in the two samples. In contrast, the two IL2 SNPs showed association...... both separately and in haplotypes with several atopic phenotypes, most significantly with IgE-mediated allergy. (single SNP P-value 0.0005 for positive skin prick test, haplotype P-value 0.019 for positive RAST test). To our knowledge, this is the first study reporting association between IL2 and Ig...

  12. Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.

    Science.gov (United States)

    Amin, N; Byrne, E; Johnson, J; Chenevix-Trench, G; Walter, S; Nolte, I M; Vink, J M; Rawal, R; Mangino, M; Teumer, A; Keers, J C; Verwoert, G; Baumeister, S; Biffar, R; Petersmann, A; Dahmen, N; Doering, A; Isaacs, A; Broer, L; Wray, N R; Montgomery, G W; Levy, D; Psaty, B M; Gudnason, V; Chakravarti, A; Sulem, P; Gudbjartsson, D F; Kiemeney, L A; Thorsteinsdottir, U; Stefansson, K; van Rooij, F J A; Aulchenko, Y S; Hottenga, J J; Rivadeneira, F R; Hofman, A; Uitterlinden, A G; Hammond, C J; Shin, S-Y; Ikram, A; Witteman, J C M; Janssens, A C J W; Snieder, H; Tiemeier, H; Wolfenbuttel, B H R; Oostra, B A; Heath, A C; Wichmann, E; Spector, T D; Grabe, H J; Boomsma, D I; Martin, N G; van Duijn, C M

    2012-11-01

    Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).

  13. Association between developmental defects of enamel and dental caries: A systematic review and meta-analysis.

    Science.gov (United States)

    Vargas-Ferreira, F; Salas, M M S; Nascimento, G G; Tarquinio, S B C; Faggion, C M; Peres, M A; Thomson, W M; Demarco, F F

    2015-06-01

    Dental caries is the main problem oral health and it is not well established in the literature if the enamel defects are a risk factor for its development. Studies have reported a potential association between developmental defects enamel (DDE) and dental caries occurrence. We investigated the association between DDE and caries in permanent dentition of children and teenagers. A systematic review was carried out using four databases (Pubmed, Web of Science, Embase, and Science Direct), which were searched from their earliest records until December 31, 2014. Population-based studies assessing differences in dental caries experience according to the presence of enamel defects (and their types) were included. PRISMA guidelines for reporting systematic reviews were followed. Meta-analysis was performed to assess the pooled effect, and meta-regression was carried out to identify heterogeneity sources. From the 2558 initially identified papers, nine studies fulfilled all inclusion criteria after checking the titles, abstracts, references, and complete reading. Seven of them were included in the meta-analysis with random model. A positive association between enamel defects and dental caries was identified; meta-analysis showed that individuals with DDE had higher pooled odds of having dental caries experience [OR 2.21 (95% CI 1.3; 3.54)]. Meta-regression analysis demonstrated that adjustment for sociodemographic factors, countries' socioeconomic status, and bias (quality of studies) explained the high heterogeneity observed. A higher chance of dental caries should be expected among individuals with enamel defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Hyponatremia improvement is associated with a reduced risk of mortality: evidence from a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Giovanni Corona

    Full Text Available Hyponatremia is the most common electrolyte disorder and it is associated with increased morbidity and mortality. However, there is no clear demonstration that the improvement of serum sodium concentration ([Na(+] counteracts the increased risk of mortality associated with hyponatremia. Thus, we performed a meta-analysis that included the published studies that addressed the effect of hyponatremia improvement on mortality.A Medline, Embase and Cochrane search was performed to retrieve all English-language studies of human subjects published up to June 30th 2014, using the following words: "hyponatremia", "hyponatraemia", "mortality", "morbidity" and "sodium". Fifteen studies satisfied inclusion criteria encompassing a total of 13,816 patients. The identification of relevant abstracts, the selection of studies and the subsequent data extraction were performed independently by two of the authors, and conflicts resolved by a third investigator. Across all fifteen studies, any improvement of hyponatremia was associated with a reduced risk of overall mortality (OR=0.57[0.40-0.81]. The association was even stronger when only those studies (n=8 reporting a threshold for serum [Na(+] improvement to >130 mmol/L were considered (OR=0.51[0.31-0.86]. The reduced mortality rate persisted at follow-up (OR=0.55[0.36-0.84] at 12 months. Meta-regression analyses showed that the reduced mortality associated with hyponatremia improvement was more evident in older subjects and in those with lower serum [Na(+] at enrollment.This meta-analysis documents for the first time that improvement in serum [Na(+] in hyponatremic patients is associated with a reduction of overall mortality.

  15. Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.

    Science.gov (United States)

    Ferreira, Manuel A R; Matheson, Melanie C; Tang, Clara S; Granell, Raquel; Ang, Wei; Hui, Jennie; Kiefer, Amy K; Duffy, David L; Baltic, Svetlana; Danoy, Patrick; Bui, Minh; Price, Loren; Sly, Peter D; Eriksson, Nicholas; Madden, Pamela A; Abramson, Michael J; Holt, Patrick G; Heath, Andrew C; Hunter, Michael; Musk, Bill; Robertson, Colin F; Le Souëf, Peter; Montgomery, Grant W; Henderson, A John; Tung, Joyce Y; Dharmage, Shyamali C; Brown, Matthew A; James, Alan; Thompson, Philip J; Pennell, Craig; Martin, Nicholas G; Evans, David M; Hinds, David A; Hopper, John L

    2014-06-01

    To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10(-9)) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10(-8)). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10(-7)) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10(-6)). By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  16. Association between individual differences in non-symbolic number acuity and math performance: a meta-analysis.

    Science.gov (United States)

    Chen, Qixuan; Li, Jingguang

    2014-05-01

    Many recent studies have examined the association between number acuity, which is the ability to rapidly and non-symbolically estimate the quantity of items appearing in a scene, and symbolic math performance. However, various contradictory results have been reported. To comprehensively evaluate the association between number acuity and symbolic math performance, we conduct a meta-analysis to synthesize the results observed in previous studies. First, a meta-analysis of cross-sectional studies (36 samples, N = 4705) revealed a significant positive correlation between these skills (r = 0.20, 95% CI = [0.14, 0.26]); the association remained after considering other potential moderators (e.g., whether general cognitive abilities were controlled). Moreover, a meta-analysis of longitudinal studies revealed 1) that number acuity may prospectively predict later math performance (r = 0.24, 95% CI = [0.11, 0.37]; 6 samples) and 2) that number acuity is retrospectively correlated to early math performance as well (r = 0.17, 95% CI = [0.07, 0.26]; 5 samples). In summary, these pieces of evidence demonstrate a moderate but statistically significant association between number acuity and math performance. Based on the estimated effect sizes, power analyses were conducted, which suggested that many previous studies were underpowered due to small sample sizes. This may account for the disparity between findings in the literature, at least in part. Finally, the theoretical and practical implications of our meta-analytic findings are presented, and future research questions are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Association between C-reactive protein and atrial fibrillation recurrence after catheter ablation: a meta-analysis.

    Science.gov (United States)

    Jiang, Zhouqin; Dai, Limeng; Song, Zhiyuan; Li, Huakang; Shu, Maoqin

    2013-09-01

    Atrial fibrillation (AF) is associated with inflammation. Increased serum C-reactive protein (CRP) levels are important representatives of an inflammatory state of AF. A variety of studies have evaluated whether increased CRP levels have an association with AF recurrence after catheter ablation. However, the results remain inconsistent, therefore, this meta-analysis was conducted to offer suggestions. Increased baseline CRP have an association with AF recurrence after catheter ablation. Electronic databases including PubMed, Embase, Medline, ISI Web of Knowledge, and ScienceDirect were searched until December 31, 2012 for any CRP-associated studies. Overall and subgroup analyses were performed. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to evaluate the associations between CRP levels and postablation AF recurrence. Statistical analysis was performed with Review Manager 5.2 and Stata 11.0. Seven available studies were identified, which included 526 patients (179 recurrence vs 347 no recurrence). Overall, increased baseline CRP levels had significant positive association with postablation AF recurrence. The SMD in the CRP levels was 0.65 units (95% CI: 0.30-0.99), and the z-score for overall effect was 3.70 (P = 0.0002). The heterogeneity test showed that there were moderate differences between individual studies (P = 0.006, I(2) = 67%). Metaregression revealed that different sample sizes of studies possibly accounted for the heterogeneity. Positive associations were also found in subgroup analyses based on sample size. When stratifying for ethnicity, similarly significant associations were found in both European (Caucasian) and Asian populations. Investigations demonstrate that baseline CRP levels are greater in patients with postablation AF recurrence. Further studies with larger sample size and delicate design for CRP should be conducted. © 2013 Wiley Periodicals, Inc.

  18. Climatic factors and community - associated methicillin-resistant Staphylococcus aureus skin and soft-tissue infections - a time-series analysis study.

    Science.gov (United States)

    Sahoo, Krushna Chandra; Sahoo, Soumyakanta; Marrone, Gaetano; Pathak, Ashish; Lundborg, Cecilia Stålsby; Tamhankar, Ashok J

    2014-08-29

    Skin and soft tissue infections caused by Staphylococcus aureus (SA-SSTIs) including methicillin-resistant Staphylococcus aureus (MRSA) have experienced a significant surge all over the world. Changing climatic factors are affecting the global burden of dermatological infections and there is a lack of information on the association between climatic factors and MRSA infections. Therefore, association of temperature and relative humidity (RH) with occurrence of SA-SSTIs (n = 387) and also MRSA (n = 251) was monitored for 18 months in the outpatient clinic at a tertiary care hospital located in Bhubaneswar, Odisha, India. The Kirby-Bauer disk diffusion method was used for antibiotic susceptibility testing. Time-series analysis was used to investigate the potential association of climatic factors (weekly averages of maximum temperature, minimum temperature and RH) with weekly incidence of SA-SSTIs and MRSA infections. The analysis showed that a combination of weekly average maximum temperature above 33 °C coinciding with weekly average RH ranging between 55% and 78%, is most favorable for the occurrence of SA-SSTIs and MRSA and within these parameters, each unit increase in occurrence of MRSA was associated with increase in weekly average maximum temperature of 1.7 °C (p = 0.044) and weekly average RH increase of 10% (p = 0.097).

  19. Association of fine particles with respiratory disease mortality: a meta-analysis.

    Science.gov (United States)

    Chang, Xuhong; Zhou, Liangjia; Tang, Meng; Wang, Bei

    2015-01-01

    Short-time exposure to high levels of fine particles (particulate matter with an aerodynamic diameter≤2.5 μm; PM2.5) may trigger respiratory disease, but this association has not been determined. The objective of this study was to evaluate and quantify the short-time exposure to fine particles on respiratory disease mortality. Published articles were obtained from electronic databases and a validity assessment was used. The meta-analysis was conducted with the incorporation of good-quality studies. After applying the inclusion criteria, 9 articles were included in the study. The methodological qualities of the published studies were good, and every study achieved a score of 3. Fine particles were significantly associated with an increase in respiratory mortality risk (for every 10 μg/m3 increment, rate difference [RD]=1.32%, 95% confidence interval [CI]: 0.95%-1.68%; p=.000). These findings indicate that short-time exposure to fine particles could increase the risk of respiratory disease mortality.

  20. Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

    Science.gov (United States)

    Loo, Sandra K.; Shtir, Corina; Doyle, Alysa E.; Mick, Eric; McGough, James J.; McCracken, James; Biederman, Joseph; Smalley, Susan L.; Cantor, Rita M.; Faraone, Stephen V.; Nelson, Stanley F.

    2012-01-01

    Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally…

  1. Association between platelet to lymphocyte ratio (PLR) and overall survival (OS) of hepatocellular carcinoma (HCC): A meta-analysis.

    Science.gov (United States)

    Hu, D-H; Yu, S-M

    2017-08-30

    Some studies investigated the association between platelet-to-lymphocyte ratio (PLR) and the survival of hepatocellular carcinoma (HCC). However, the results remained inconclusive. Thus, we performed this meta-analysis. Published studies were searched in PubMed and EMBASE. The strength of association was assessed by calculating odds ratios (OR) and 95% confidence interval (CI). In total, 6 studies with 1446 HCC patients were included in this meta-analysis. HCC with higher PLR showed an increased death risk (OR = 1.59; 95%CI, 1.15-2.20; P < 0.0001). However, the heterogeneity was high (I2=89.2%). When the study by Li et al. was excluded, the heterogeneity decreased (I2=20%). Further, the result was still positive (OR = 1.70; 95%CI, 1.42-2.04; P < 0.00001). In conclusion, this meta-analysis suggested that PLR was significantly associated with the OS of HCC.

  2. Association between the rs7574865 polymorphism of STAT4 and rheumatoid arthritis: a meta-analysis.

    Science.gov (United States)

    Lee, Young Ho; Woo, Jin-Hyun; Choi, Seong Jae; Ji, Jong Dae; Song, Gwan Gyu

    2010-03-01

    The aim of this study was to determine whether the rs7574865 polymorphism of STAT4 (signal transducers and activators of transcription 4) confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. A meta-analysis was conducted on the T allele of the STAT4 rs7574865 polymorphism in 15 studies containing 16,088 RA patients and 16,509 normal control subjects. Meta-analysis revealed an association between RA and the STAT4 rs7574865 T allele in all subjects (OR = 1.271, 95% CI = 1.197-1.350, P rs7574865 T allele was found to be significantly associated with RA in Europeans and Asians (OR = 1.300, 95% CI = 1.195-1.414, P rs7574865 polymorphism is associated with RA susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.

  3. Meta-analysis of the association between APC promoter methylation and colorectal cancer.

    Science.gov (United States)

    Ding, Zhenyu; Jiang, Tong; Piao, Ying; Han, Tao; Han, Yaling; Xie, Xiaodong

    2015-01-01

    Previous studies investigating the association between adenomatous polyposis coli (APC) gene promoter methylation and colorectal cancer (CRC) have yielded conflicting results. The aim of this study was to comprehensively evaluate the potential application of the detection of APC promoter methylation to the prevention and treatment of CRC. PubMed, Embase, and MEDLINE (results updated to October 2014) were searched for relevant studies. The effect size was defined as the weighted odds ratio (OR), which was calculated using either the fixed-effects or random-effects model. Prespecified subgroup and sensitivity analyses were conducted to evaluate potential heterogeneity among the included studies. Nineteen studies comprising 2,426 participants were selected for our meta-analysis. The pooled results of nine studies comprising a total of 740 subjects indicated that APC promoter methylation was significantly associated with CRC risk (pooled OR 5.53; 95% confidence interval [CI] 3.50-8.76; PAPC promoter methylation and the presence of CRC metastasis, and the pooled OR was 0.80 (95% CI 0.44-1.46; P=0.47). A meta-analysis conducted with four studies with a total of 467 patients found no significant correlation between APC promoter methylation and the presence of colorectal adenoma (pooled OR 1.85; 95% CI 0.67-5.10; P=0.23). No significant correlation between APC promoter methylation and patients' Dukes' stage, TNM stage, differentiation grade, age, or sex was identified. In conclusion, APC promoter methylation was found to be significantly associated with a higher risk of developing CRC. The findings indicate that APC promoter methylation may be a potential biomarker for the carcinogenesis of CRC.

  4. An innovative procedure of genome-wide association analysis fits studies on germplasm population and plant breeding.

    Science.gov (United States)

    He, Jianbo; Meng, Shan; Zhao, Tuanjie; Xing, Guangnan; Yang, Shouping; Li, Yan; Guan, Rongzhan; Lu, Jiangjie; Wang, Yufeng; Xia, Qiuju; Yang, Bing; Gai, Junyi

    2017-11-01

    The innovative RTM-GWAS procedure provides a relatively thorough detection of QTL and their multiple alleles for germplasm population characterization, gene network identification, and genomic selection strategy innovation in plant breeding. The previous genome-wide association studies (GWAS) have been concentrated on finding a handful of major quantitative trait loci (QTL), but plant breeders are interested in revealing the whole-genome QTL-allele constitution in breeding materials/germplasm (in which tremendous historical allelic variation has been accumulated) for genome-wide improvement. To match this requirement, two innovations were suggested for GWAS: first grouping tightly linked sequential SNPs into linkage disequilibrium blocks (SNPLDBs) to form markers with multi-allelic haplotypes, and second utilizing two-stage association analysis for QTL identification, where the markers were preselected by single-locus model followed by multi-locus multi-allele model stepwise regression. Our proposed GWAS procedure is characterized as a novel restricted two-stage multi-locus multi-allele GWAS (RTM-GWAS, https://github.com/njau-sri/rtm-gwas ). The Chinese soybean germplasm population (CSGP) composed of 1024 accessions with 36,952 SNPLDBs (generated from 145,558 SNPs, with reduced linkage disequilibrium decay distance) was used to demonstrate the power and efficiency of RTM-GWAS. Using the CSGP marker information, simulation studies demonstrated that RTM-GWAS achieved the highest QTL detection power and efficiency compared with the previous procedures, especially under large sample size and high trait heritability conditions. A relatively thorough detection of QTL with their multiple alleles was achieved by RTM-GWAS compared with the linear mixed model method on 100-seed weight in CSGP. A QTL-allele matrix (402 alleles of 139 QTL × 1024 accessions) was established as a compact form of the population genetic constitution. The 100-seed weight QTL-allele matrix was

  5. Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk

    Science.gov (United States)

    Lindström, Sara; Thompson, Deborah J.; Paterson, Andrew D.; Li, Jingmei; Gierach, Gretchen L.; Scott, Christopher; Stone, Jennifer; Douglas, Julie A.; dos-Santos-Silva, Isabel; Fernandez-Navarro, Pablo; Verghase, Jajini; Smith, Paula; Brown, Judith; Luben, Robert; Wareham, Nicholas J.; Loos, Ruth J.F.; Heit, John A.; Pankratz, V. Shane; Norman, Aaron; Goode, Ellen L.; Cunningham, Julie M.; deAndrade, Mariza; Vierkant, Robert A.; Czene, Kamila; Fasching, Peter A.; Baglietto, Laura; Southey, Melissa C.; Giles, Graham G.; Shah, Kaanan P.; Chan, Heang-Ping; Helvie, Mark A.; Beck, Andrew H.; Knoblauch, Nicholas W.; Hazra, Aditi; Hunter, David J.; Kraft, Peter; Pollan, Marina; Figueroa, Jonine D.; Couch, Fergus J.; Hopper, John L.; Hall, Per; Easton, Douglas F.; Boyd, Norman F.; Vachon, Celine M.; Tamimi, Rulla M.

    2015-01-01

    Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5×10−8) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B, SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23, TMEM184B). Four of these regions are known breast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (P<0.05) in a large meta-analysis. These results provide further evidence of a shared genetic basis between mammographic density and breast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease susceptibility loci. PMID:25342443

  6. Warfarin resumption following anticoagulant-associated intracranial hemorrhage: A systematic review and meta-analysis.

    Science.gov (United States)

    Chai-Adisaksopha, Chatree; Iorio, Alfonso; Hillis, Christopher; Siegal, Deborah; Witt, Daniel M; Schulman, Sam; Crowther, Mark

    2017-12-01

    This study aims to assess the effect of warfarin resumption in patients who experienced warfarin-associated intracranial hemorrhage (ICH). We conducted a systematic review and meta-analysis of studies evaluating the outcomes of adult patients who survived warfarin-associated ICH. We included studies that compared patients who resumed warfarin versus those who did not. Of 3145 studies screened, ten observational studies were included in the final analysis. Death occurred in 181 of 968 patients (18.7%) who resumed warfarin and 834 of 2579 (32.3%) who did not resume warfarin (RR 0.51, 95% CI 0.34 to 0.76, P=0.0009). Ischemic stroke occurred in 32 of 902 (3.5%) patients who resumed warfarin and 172 of 2467 (7.0%) patients who did not resume warfarin (RR 0.56, 95% CI 0.39 to 0.82, P=0.002). Venous thromboembolism occurred in 4 of 224 (1.8%) patients who resumed warfarin and of 33 of 681 (4.8%) patients who did not resume warfarin (RR 0.39, 95% CI, 0.15 to 1.03, P=0.06). Recurrent ICH occurred in 200 of 2994 (6.7%) patients who resumed warfarin and 358 of 4652 (7.7%) patients who did not resume warfarin (RR 0.89, 95% CI 0.65 to 1.23, P=0.49). The study suggests that warfarin resumption is associated with significant reduction in ischemic stroke and venous thromboembolism when compared to no warfarin resumption in patients who experience warfarin-associated ICH. Although these results are strongly supportive of restarting anticoagulation, prospective studies are required to confirm our results due to the high likelihood of bias in the included studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Prefrontal cortex and somatosensory cortex in tactile crossmodal association: an independent component analysis of ERP recordings.

    Directory of Open Access Journals (Sweden)

    Yixuan Ku

    2007-08-01

    Full Text Available Our previous studies on scalp-recorded event-related potentials (ERPs showed that somatosensory N140 evoked by a tactile vibration in working memory tasks was enhanced when human subjects expected a coming visual stimulus that had been paired with the tactile stimulus. The results suggested that such enhancement represented the cortical activities involved in tactile-visual crossmodal association. In the present study, we further hypothesized that the enhancement represented the neural activities in somatosensory and frontal cortices in the crossmodal association. By applying independent component analysis (ICA to the ERP data, we found independent components (ICs located in the medial prefrontal cortex (around the anterior cingulate cortex, ACC and the primary somatosensory cortex (SI. The activity represented by the IC in SI cortex showed enhancement in expectation of the visual stimulus. Such differential activity thus suggested the participation of SI cortex in the task-related crossmodal association. Further, the coherence analysis and the Granger causality spectral analysis of the ICs showed that SI cortex appeared to cooperate with ACC in attention and perception of the tactile stimulus in crossmodal association. The results of our study support with new evidence an important idea in cortical neurophysiology: higher cognitive operations develop from the modality-specific sensory cortices (in the present study, SI cortex that are involved in sensation and perception of various stimuli.

  8. Association between MASP-2 gene polymorphism and risk of infection diseases: A meta-analysis.

    Science.gov (United States)

    Fu, Jie; Wang, Jingqiu; Luo, Yanping; Zhang, Lifeng; Zhang, Yuan; Dong, Xinfang; Yu, Hongjuan; Cao, Mingqiang; Ma, Xingming

    2016-11-01

    The role of MASP-2 is vital in the process of complement activation by the lectin pathway. It is generally considered that the functional activation of MASP-2 contribute to the infection disease development process. To analyze the association between MASP-2 functional gene (rs72550870) polymorphism and the infection disease risk by a meta-analysis. Relevant case-control studies were identified by searching Cochrane Library, PubMed, Emabase, DOAJ, CAB Abstracts, CSA, CINAHL, EBSCO, Scopus, Global Health, Index Copernicus, CA, China National Knowledge Infrastructure (CNKI) databases up to 10th January 2016. The data were extracted and the methodological quality of studies were evaluated. The STATA 12.0 software was used to perform statistical analysis. 9 studies were included. There was no significant association between masp-2 gene (p.D120G, rs72550870) polymorphism and the risk of infection disease under the allele model (G vs. A: OR = 0.89, 95%CI = 0.66-1.21)(P = 0.445>0.05) and the recessive model (AG + GG vs.AA: OR = 0.88, 95%CI = 0.65-1.20) (P = 0.428>0.05). This is the first comprehensive meta-analysis indicates that the MASP-2 functional gene (rs72550870) polymorphism is not associated with the infection diseases, and the key functional gene polymorphism of rs72550870 did not increase susceptibility to the infection diseases. Similarly, there were no obvious difference in subgroup analysis based on geographical areas and pathogenic microorganisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Association between XRCC1 polymorphism 399 G->A and glioma among Caucasians: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Jacobs Daniel I

    2012-10-01

    Full Text Available Abstract Background The x-ray cross complementing group 1 gene (XRCC1 is crucial to proper repair of DNA damage such as single-strand DNA breaks. A non-synonymous polymorphism in XRCC1, 399 G → A, has been shown to reduce effectiveness of such DNA repair and has been associated with the risk of certain cancers. The known risk for glioma from high dose ionizing radiation makes associations between this polymorphism and glioma of particular interest. Methods A systematic literature review and meta-analysis was conducted to explore the association between XRCC1 399 G → A and glioma. Subgroup analyses by grade, gender, genotyping method, country in which study was conducted, and study size were conducted when data were available and validity of the results were assessed by influence analyses and exploration of potential publication bias. Results Six studies were eligible for meta-analysis including data on 2,362 Caucasian glioma cases and 3,085 Caucasian controls. Pooled analysis yielded a significant association between the variant of interest and risk of glioma (OR = 1.17, 95% CI: 1.05-1.30 which was found to be disproportionately driven by a single study. Exclusion of this study, in an influence analysis, produced no statistically significant evidence of association with glioma (OR = 1.10, 95% CI: 0.98-1.23, and no evidence of publication bias. Conclusions This meta-analysis does not suggest a major role of the XRCC1 399 G → A polymorphism in influencing risk of glioma among Caucasians. Future studies should report data separately for glioma subtypes to permit stratified analyses for Grade III and Grade IV glioma and examine other polymorphisms in this gene.

  10. Association between polymorphisms in ERCC2 gene and oral cancer risk: evidence from a meta-analysis

    International Nuclear Information System (INIS)

    Zhang, Enjiao; Cui, Zhigang; Xu, Zhongfei; Duan, Weiyi; Huang, Shaohui; Tan, Xuexin; Yin, Zhihua; Sun, Changfu; Lu, Li

    2013-01-01

    Excision repair cross-complementing group 2 (ERCC2) plays important roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of ERCC2 gene are suspected to influence the risks of oral cancer. We performed a meta-analysis to systematically summarize the possible association of ERCC2 rs1799793 and rs13181 polymorphisms with oral cancer risks. We retrieved the relevant articles from PubMed and Embase databases. Studies were selected using specific criteria. ORs and 95% CIs were calculated to assess the association. All analyses were performed using the Stata software. Six studies were included in this meta-analysis. There were no significant associations between ERCC2 rs1799793 and rs13181 polymorphism with overall oral cancer risk. In the stratified analysis by ethnicity, no significant associations were found. In the stratified analysis by tumor type, the risk of oral leukoplakia was significant associated with rs13181 polymorphism (AC vs. AA: OR = 1.28, 95% CI = 1.01-1.62, P = 0.546 for heterogeneity, I 2 = 0.0%; CC vs. AA: OR = 1.94, 95% CI = 0.99-3.79, P = 0.057 for heterogeneity, I 2 = 60.1%; dominant model AC + CC vs. AA: OR = 1.35, 95% CI = 1.08–1.69, P = 0.303 for heterogeneity, I 2 = 17.6%; allele C vs. A: OR = 1.38, 95% CI = 1.04–1.82. P = 0.043 for heterogeneity, I 2 = 56.4%). Rs13181 in ERCC2 gene might be associated with oral leukoplakia risk

  11. Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

    Directory of Open Access Journals (Sweden)

    Niu Nifang

    2012-09-01

    Full Text Available Abstract Background Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs that might contribute to taxane response, we performed a genome-wide association study (GWAS for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs, followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. Methods GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196 and NSCLC (A549 cell lines. Results 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values -4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667, significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA hsa-miR-584 or hsa-miR-1468. Conclusions GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel.

  12. Association of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with a systematic review and meta-analysis.

    Science.gov (United States)

    Hartwig, Fernando Pires; Horta, Bernardo Lessa; Smith, George Davey; de Mola, Christian Loret; Victora, Cesar Gomes

    2016-10-01

    Milk intake has been associated with lower blood pressure (BP) in observational studies, and randomized controlled trials suggested that milk-derived tripeptides have BP-lowering effects. Milk intake has also been associated with body mass index (BMI). Nevertheless, it is unclear whether increasing milk consumption would reduce BP in the general population. We investigated the association of milk intake with obesity and BP using genetically-defined lactase persistence (LP) based on the rs4988235 polymorphism in a Mendelian randomization design in the 1982 Pelotas (Southern Brazil) Birth Cohort. These results were combined with published reports identified through a systematic review using meta-analysis. In the 1982 Pelotas Birth Cohort, milk intake was 42 [95% confidence interval (CI): 18; 67) ml/day higher in LP individuals. In conventional observational analysis, each 1-dl/day increase in milk intake was associated with -0.26 (95% CI: -0.33; -0.19) kg/m 2 in BMI and -0.31 (95% CI: -0.46; -0.16) and -0.35 (95% CI: -0.46; -0.23) mmHg in systolic and diastolic BP, respectively. These results were not corroborated when analysing LP status, but confidence intervals were large. In random effects meta-analysis, LP individuals presented higher BMI [0.17 (95% CI: 0.07; 0.27) kg/m 2 ] and higher odds of overweight-obesity [1.09 (95% CI: 1.02; 1.17)]. There were no reliable associations for BP. Our study supports that LP is positively associated with obesity, suggesting that the negative association of milk intake with obesity is likely due to limitations of conventional observational studies. Our findings also do not support that increased milk intake leads to lower BP. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

  13. Identification of a gene module associated with BMD through the integration of network analysis and genome-wide association data.

    Science.gov (United States)

    Farber, Charles R

    2010-11-01

    Bone mineral density (BMD) is influenced by a complex network of gene interactions; therefore, elucidating the relationships between genes and how those genes, in turn, influence BMD is critical for developing a comprehensive understanding of osteoporosis. To investigate the role of transcriptional networks in the regulation of BMD, we performed a weighted gene coexpression network analysis (WGCNA) using microarray expression data on monocytes from young individuals with low or high BMD. WGCNA groups genes into modules based on patterns of gene coexpression. and our analysis identified 11 gene modules. We observed that the overall expression of one module (referred to as module 9) was significantly higher in the low-BMD group (p = .03). Module 9 was highly enriched for genes belonging to the immune system-related gene ontology (GO) category "response to virus" (p = 7.6 × 10(-11)). Using publically available genome-wide association study data, we independently validated the importance of module 9 by demonstrating that highly connected module 9 hubs were more likely, relative to less highly connected genes, to be genetically associated with BMD. This study highlights the advantages of systems-level analyses to uncover coexpression modules associated with bone mass and suggests that particular monocyte expression patterns may mediate differences in BMD. © 2010 American Society for Bone and Mineral Research.

  14. Association between variations in the disrupted in schizophrenia 1 gene and schizophrenia: A meta-analysis.

    Science.gov (United States)

    Xu, Yiliang; Ren, Jun; Ye, Haihong

    2018-04-20

    Schizophrenia is a severe psychiatric disorder. Genetic and functional studies have strongly implicated the disrupted in schizophrenia 1 gene (DISC1) as a candidate susceptibility gene for schizophrenia. Moreover, recent association studies have indicated that several DISC1 single nucleotide polymorphisms (SNPs) are associated with schizophrenia. However, the association is hardly replicate in different ethnic group. Here, we performed a meta-analysis of the association between DISC1 SNPs and schizophrenia in which the samples were divided into subgroups according to ethnicity. Both rs3738401 and rs821616 showed not significantly association with schizophrenia in the Caucasian, Asian, Japanese or Han Chinese populations. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Multiple Genes Related to Muscle Identified through a Joint Analysis of a Two-stage Genome-wide Association Study for Racing Performance of 1,156 Thoroughbreds

    Directory of Open Access Journals (Sweden)

    Dong-Hyun Shin

    2015-06-01

    Full Text Available Thoroughbred, a relatively recent horse breed, is best known for its use in horse racing. Although myostatin (MSTN variants have been reported to be highly associated with horse racing performance, the trait is more likely to be polygenic in nature. The purpose of this study was to identify genetic variants strongly associated with racing performance by using estimated breeding value (EBV for race time as a phenotype. We conducted a two-stage genome-wide association study to search for genetic variants associated with the EBV. In the first stage of genome-wide association study, a relatively large number of markers (~54,000 single-nucleotide polymorphisms, SNPs were evaluated in a small number of samples (240 horses. In the second stage, a relatively small number of markers identified to have large effects (170 SNPs were evaluated in a much larger number of samples (1,156 horses. We also validated the SNPs related to MSTN known to have large effects on racing performance and found significant associations in the stage two analysis, but not in stage one. We identified 28 significant SNPs related to 17 genes. Among these, six genes have a function related to myogenesis and five genes are involved in muscle maintenance. To our knowledge, these genes are newly reported for the genetic association with racing performance of Thoroughbreds. It complements a recent horse genome-wide association studies of racing performance that identified other SNPs and genes as the most significant variants. These results will help to expand our knowledge of the polygenic nature of racing performance in Thoroughbreds.

  16. Evaluation of potential novel variations and their interactions related to bipolar disorders: analysis of genome-wide association study data.

    Science.gov (United States)

    Acikel, Cengizhan; Aydin Son, Yesim; Celik, Cemil; Gul, Husamettin

    2016-01-01

    Multifactor dimensionality reduction (MDR) is a nonparametric approach that can be used to detect relevant interactions between single-nucleotide polymorphisms (SNPs). The aim of this study was to build the best genomic model based on SNP associations and to identify candidate polymorphisms that are the underlying molecular basis of the bipolar disorders. This study was performed on Whole-Genome Association Study of Bipolar Disorder (dbGaP [database of Genotypes and Phenotypes] study accession number: phs000017.v3.p1) data. After preprocessing of the genotyping data, three classification-based data mining methods (ie, random forest, naïve Bayes, and k-nearest neighbor) were performed. Additionally, as a nonparametric, model-free approach, the MDR method was used to evaluate the SNP profiles. The validity of these methods was evaluated using true classification rate, recall (sensitivity), precision (positive predictive value), and F-measure. Random forests, naïve Bayes, and k-nearest neighbors identified 16, 13, and ten candidate SNPs, respectively. Surprisingly, the top six SNPs were reported by all three methods. Random forests and k-nearest neighbors were more successful than naïve Bayes, with recall values >0.95. On the other hand, MDR generated a model with comparable predictive performance based on five SNPs. Although different SNP profiles were identified in MDR compared to the classification-based models, all models mapped SNPs to the DOCK10 gene. Three classification-based data mining approaches, random forests, naïve Bayes, and k-nearest neighbors, have prioritized similar SNP profiles as predictors of bipolar disorders, in contrast to MDR, which has found different SNPs through analysis of two-way and three-way interactions. The reduced number of associated SNPs discovered by MDR, without loss in the classification performance, would facilitate validation studies and decision support models, and would reduce the cost to develop predictive and

  17. A study on association and correlation of lip and finger print pattern analysis for gender identification

    Directory of Open Access Journals (Sweden)

    Surapaneni Ratheesh Kumar Nandan

    2015-01-01

    Conclusion: Lip print analysis is a challenging area in the personal identification during forensic dentistry examination. The study revealed the weaker correlation and approachable significance of lip and finger print pattern in gender identification. Future studies should be encouraged in the direction of software based identification for lip and finger print analysis in gender identification. Such studies may benefit this study pattern in more accurate way.

  18. A Meta-analysis on the Association Between Emotional Awareness and Borderline Personality Pathology.

    Science.gov (United States)

    Derks, Youri P M J; Westerhof, Gerben J; Bohlmeijer, Ernst T

    2017-06-01

    Theories on borderline personality pathology (BPP) suggest that characteristic emotional dysregulation is due to low levels of emotional awareness or alexithymia. This study is the first meta-analysis to systematically review and analyze the evidence. A systematic search of the literature was performed using PsycInfo, Web of Science/MEDLINE, and Scopus. The term "borderline personality disorder" was searched for in conjunction with "emotional awareness," "emotional self-awareness," "emotion recognition," "alexithymia," "emotional processing," "emotional granularity," "emotional intelligence," or "emotion regulation." All references in the included studies were reviewed for additional relevant articles. Thirty-nine studies were then evaluated in a random effects meta-analysis to assess the association between BPP and emotional awareness. An overall moderate positive association between BPP and emotional awareness was significant (r = 0.359; 95% CI [0.283, 0.431]; Z = 8.678; p emotional awareness and those using alexithymia instruments. The strongest associations with regard to aspects of alexithymia were found for difficulties in identifying and describing emotions rather than externally oriented thinking. The results corroborate a moderate relationship between low emotional awareness and BPP. However, the mono-method self-report used in almost all studies is found problematic and precludes drawing definite conclusions. Since leading psychotherapeutic treatments strongly focus on increasing emotional awareness, future research should address this issue and further examine to what extent low levels of emotional awareness, particularly alexithymia, can be treated.

  19. Association between water fluoride and the level of children's intelligence: a dose-response meta-analysis.

    Science.gov (United States)

    Duan, Q; Jiao, J; Chen, X; Wang, X

    2018-01-01

    Higher fluoride concentrations in water have inconsistently been associated with the levels of intelligence in children. The following study summarizes the available evidence regarding the strength of association between fluoridated water and children's intelligence. Meta-analysis. PubMed, Embase, and Cochrane Library databases were systematically analyzed from November 2016. Observational studies that have reported on intelligence levels in relation to high and low water fluoride contents, with 95% confidence intervals (CIs) were included. Further, the results were pooled using inverse variance methods. The correlation between water fluoride concentration and intelligence level was assessed by a dose-response meta-analysis. Twenty-six studies reporting data on 7258 children were included. The summary results indicated that high water fluoride exposure was associated with lower intelligence levels (standardized mean difference : -0.52; 95% CI: -0.62 to -0.42; P intelligence (P intelligence levels. Greater exposure to high levels of fluoride in water was significantly associated with reduced levels of intelligence in children. Therefore, water quality and exposure to fluoride in water should be controlled in areas with high fluoride levels in water. Copyright © 2017. Published by Elsevier Ltd.

  20. Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

    Science.gov (United States)

    Lasram, Khaled; Ben Halim, Nizar; Hsouna, Sana; Kefi, Rym; Arfa, Imen; Ghazouani, Welid; Jamoussi, Henda; Benrahma, Houda; Kharrat, Najla; Rebai, Ahmed; Ben Ammar, Slim; Bahri, Sonia; Barakat, Abdelhamid; Abid, Abdelmajid; Abdelhak, Sonia

    2014-01-01

    Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.). Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, and P = 0.007). Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, and P < 10−3 and OR = 1.33, 95% CI = 1.13–1.56, and P = 0.001, resp.). Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs. PMID:25165692

  1. Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Khaled Lasram

    2014-01-01

    Full Text Available Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.. Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, and P=0.007. Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, and P<10-3 and OR = 1.33, 95% CI = 1.13–1.56, and P=0.001, resp.. Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs.

  2. ASSOCIATION RULE ANALYSIS FOR TOUR ROUTE RECOMMENDATION AND APPLICATION TO WCTSNOP

    Directory of Open Access Journals (Sweden)

    H. Fang

    2017-09-01

    Full Text Available The increasing E-tourism systems provide intelligent tour recommendation for tourists. In this sense, recommender system can make personalized suggestions and provide satisfied information associated with their tour cycle. Data mining is a proper tool that extracting potential information from large database for making strategic decisions. In the study, association rule analysis based on FP-growth algorithm is applied to find the association relationship among scenic spots in different cities as tour route recommendation. In order to figure out valuable rules, Kulczynski interestingness measure is adopted and imbalance ratio is computed. The proposed scheme was evaluated on Wangluzhe cultural tourism service network operation platform (WCTSNOP, where it could verify that it is able to quick recommend tour route and to rapidly enhance the recommendation quality.

  3. Microarray Study of Pathway Analysis Expression Profile Associated with MicroRNA-29a with Regard to Murine Cholestatic Liver Injuries

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    Sung-Chou Li

    2016-03-01

    Full Text Available Accumulating evidence demonstrates that microRNA-29 (miR-29 expression is prominently decreased in patients with hepatic fibrosis, which consequently stimulates hepatic stellate cells’ (HSCs activation. We used a cDNA microarray study to gain a more comprehensive understanding of genome-wide gene expressions by adjusting miR-29a expression in a bile duct-ligation (BDL animal model. Methods: Using miR-29a transgenic mice and wild-type littermates and applying the BDL mouse model, we characterized the function of miR-29a with regard to cholestatic liver fibrosis. Pathway enrichment analysis and/or specific validation were performed for differentially expressed genes found within the comparisons. Results: Analysis of the microarray data identified a number of differentially expressed genes due to the miR-29a transgene, BDL, or both. Additional pathway enrichment analysis revealed that TGF-β signaling had a significantly differential activated pathway depending on the occurrence of miR-29a overexpression or the lack thereof. Furthermore, overexpression was found to elicit changes in Wnt/β-catenin after BDL. Conclusion: This study verified that an elevated miR-29a level could alleviate liver fibrosis caused by cholestasis. Furthermore, the protective effects of miR-29a correlate with the downregulation of TGF-β and associated with Wnt/β-catenin signal pathway following BDL.

  4. Association analysis of multiple traits by an approach of combining ...

    Indian Academy of Sciences (India)

    Lili Chen

    diseases. Joint analysis of multiple traits can increase statistical power of association analysis and uncover the underlying genetic ... genthaler and Thilly 2007), the combined multivariate and ... Because of using reverse regression model, our.

  5. The association between miR-499 polymorphism and cancer susceptibility: a meta-analysis.

    Science.gov (United States)

    Xu, Zhongfei; Zhang, Enjiao; Duan, Weiyi; Sun, Changfu; Bai, Shuang; Tan, Xuexin

    2015-01-01

    MicroRNAs are a class of new noncoding RNA that play important roles in the pathogenesis of tumor. Rs3746444 in miR-499 is suggested to be associated with cancer susceptibility. In the present study, we assess the association between miR-499 rs3746444 polymorphism and cancer susceptibility through a meta-analysis. We searched relevant articles from the PubMed and Embase databases. We screened all the resulting articles for adherence to the inclusion and exclusion criteria. The associations between miR-499 polymorphism and cancer susceptibility were estimated by computing the odds ratios (ORs) and 95% confidence intervals (CIs). All analyses were performed using Stata software. There are 18 datasets included in the analysis. Statistically significant associations were found between the miR-499 rs3746444 polymorphism and susceptibility to cancer (GG versus AA: OR =1.24, 95% CI: 1.01-1.52; G versus A: OR =1.11, 95% CI: 1.01-1.23). A subsequent analysis, on the basis of ethnicity for the population characteristic, showed that Asians had increased susceptibility to cancer (GG versus AA: OR =1.32, 95% CI: 1.09-1.59; GG + AG versus AA: OR = 1.17, 95% CI: 1.01-1.37). In the subgroup analysis of tumor type, none of the genetic models had statistically significant results. The meta-regression suggested that race and cancer types are not the source of heterogeneity in the present meta-analysis. No publication bias was detected by either the inverted funnel plot or Egger's test. Rs3746444 in miR-499 might be related to susceptibility to cancer.

  6. Association between dietary nitrate and nitrite intake and sitespecific cancer risk: evidence from observational studies.

    Science.gov (United States)

    Xie, Li; Mo, Miao; Jia, Hui-Xun; Liang, Fei; Yuan, Jing; Zhu, Ji

    2016-08-30

    Epidemiological studies have reported inconsistent findings on the association between dietary nitrate and nitrite intake and cancer risk. We performed a meta-analysis of epidemiological studies to summarize available evidence on the association between dietary nitrate and nitrite intake and cancer risk from published prospective and case-control studies. PubMed database was searched to identify eligible publications through April 30th, 2016. Study-specific relative risks (RRs) with corresponding 95% confidence interval (CI) from individual studies were pooled by using random- or fixed- model, and heterogeneity and publication bias analyses were conducted. Data from 62 observational studies, 49 studies for nitrates and 51 studies for nitrites, including a total of 60,627 cancer cases were analyzed. Comparing the highest vs. lowest levels, dietary nitrate intake was inversely associated with gastric cancer risk (RR = 0.78; 95%CI = 0.67-0.91) with moderate heterogeneity (I2 = 42.3%). In contrast, dietary nitrite intake was positively associated with adult glioma and thyroid cancer risk with pooled RR of 1.21 (95%CI = 1.03-1.42) and 1.52 (95%CI = 1.12-2.05), respectively. No significant associations were found between dietary nitrate/nitrite and cancers of the breast, bladder, colorectal, esophagus, renal cell, non-Hodgkin lymphoma, ovarian, and pancreas. The present meta-analysis provided modest evidence that positive associations of dietary nitrate and negative associations of dietary nitrite with certain cancers.

  7. Meta-analysis of 32 genome-wide linkage studies of schizophrenia

    Science.gov (United States)

    Ng, MYM; Levinson, DF; Faraone, SV; Suarez, BK; DeLisi, LE; Arinami, T; Riley, B; Paunio, T; Pulver, AE; Irmansyah; Holmans, PA; Escamilla, M; Wildenauer, DB; Williams, NM; Laurent, C; Mowry, BJ; Brzustowicz, LM; Maziade, M; Sklar, P; Garver, DL; Abecasis, GR; Lerer, B; Fallin, MD; Gurling, HMD; Gejman, PV; Lindholm, E; Moises, HW; Byerley, W; Wijsman, EM; Forabosco, P; Tsuang, MT; Hwu, H-G; Okazaki, Y; Kendler, KS; Wormley, B; Fanous, A; Walsh, D; O’Neill, FA; Peltonen, L; Nestadt, G; Lasseter, VK; Liang, KY; Papadimitriou, GM; Dikeos, DG; Schwab, SG; Owen, MJ; O’Donovan, MC; Norton, N; Hare, E; Raventos, H; Nicolini, H; Albus, M; Maier, W; Nimgaonkar, VL; Terenius, L; Mallet, J; Jay, M; Godard, S; Nertney, D; Alexander, M; Crowe, RR; Silverman, JM; Bassett, AS; Roy, M-A; Mérette, C; Pato, CN; Pato, MT; Roos, J Louw; Kohn, Y; Amann-Zalcenstein, D; Kalsi, G; McQuillin, A; Curtis, D; Brynjolfson, J; Sigmundsson, T; Petursson, H; Sanders, AR; Duan, J; Jazin, E; Myles-Worsley, M; Karayiorgou, M; Lewis, CM

    2009-01-01

    A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (PSR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for ‘aggregate’ genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. PMID:19349958

  8. A genome-wide association study of corneal astigmatism: The CREAM Consortium

    OpenAIRE

    Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.

    2018-01-01

    Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts we...

  9. A genome-wide association study of corneal astigmatism: The CREAM Consortium

    OpenAIRE

    Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.

    2018-01-01

    Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts wer...

  10. A genome-wide association study of corneal astigmatism: The CREAM Consortium.

    OpenAIRE

    Shah, Rupal L; Li, Qing; Zhao, Wanting; Tedja, Milly S; Tideman, J Willem L; Khawaja, Anthony P; Fan, Qiao; Yazar, Seyhan; Williams, Katie M; Verhoeven, Virginie J M; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J

    2018-01-01

    Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry...

  11. A genome-wide association study of corneal astigmatism : The CREAM Consortium

    OpenAIRE

    Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.

    2018-01-01

    Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohor...

  12. A genome-wide association study of corneal astigmatism:The CREAM consortium

    OpenAIRE

    Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.

    2018-01-01

    Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohort...

  13. Meta-analysis of the association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss.

    Science.gov (United States)

    Li, Xuejiao; Liu, Yukun; Zhang, Rui; Tan, Jianping; Chen, Libin; Liu, Yinglin

    2015-04-11

    The association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and recurrent pregnancy loss (RPL) risk is still contradictory. We thus performed a meta-analysis. Relevant studies were searched for in PubMed, Web of Science, Embase, and Cochrane Library. An odds ratio (OR) with a 95% confidence interval (CI) was used to assess the association between PAI-1 4G/5G polymorphism and RPL risk. A total of 22 studies with 4306 cases and 3076 controls were included in this meta-analysis. We found that PAI-1 4G/5G polymorphism was significantly associated with an increased RPL risk (OR=1.89; 95% CI 1.34-2.67; P=0.0003). In the subgroup analysis by race, PAI-1 4G/5G polymorphism was significantly associated with an increased RPL risk in Caucasians (OR=2.23; 95% CI 1.44-3.46; P=0.0003). However, no significant association was observed in Asians (OR=1.47; 95% CI 0.84-2.59; P=0.18). In conclusion, this meta-analysis suggests that PAI-1 4G/5G polymorphism might be associated with RPL development in Caucasians.

  14. Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis.

    Science.gov (United States)

    Lee, Young Ho; Kim, Jae-Hoon; Song, Gwan Gyu

    2015-01-01

    The aim of this study was to explore whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with susceptibility to fibromyalgia and fibromyalgia impact questionnaire (FIQ) score in fibromyalgia patients. We conducted a meta-analysis of the associations of the COMT Val158Met polymorphism with fibromyalgia risk as well as FIQ score in fibromyalgia patients. A total of 993 fibromyalgia patients and 778 controls from 10 studies on the COMT Val158Met polymorphism and 538 fibromyalgia patients from 5 studies on the COMT Val158Met polymorphism and FIQ score were included in this meta-analysis. The meta-analysis revealed an association between fibromyalgia and the COMT Met/Met + Val/Met genotype in all study subjects (odds ratio (OR) 1.635, 95 % confidence interval (CI) 1.029-2.597, p = 0.037). However, stratification by ethnicity indicated no association between the Met/Met + Val/Met genotype and fibromyalgia in the European and Turkish populations (OR 1.202, 95 % CI 0.876-1.649, p = 0.255; OR 2.132, 95 % CI 0.764-5.949, p = 0.148, respectively). Analysis using other genetic models showed no association between the COMT Val158Met polymorphism and fibromyalgia. The meta-analysis also revealed that the FIQ score was significantly higher in individuals with the COMT Met/Met genotype than in those with the Val/Val genotype [weighted mean difference (WMD) = 14.39, 95 % CI 3.316-25.48, p = 0.011] and the Val/Met genotype (WMD = 5.108, 95 % CI 2.212-4.891, p = 0.021). This meta-analysis identified an association between fibromyalgia risk and the COMT Val158Met polymorphism as well as the FIQ score in fibromyalgia patients.

  15. Schizophrenia symptomatic associations with diffusion tensor imaging measured fractional anisotropy of brain: a meta-analysis

    International Nuclear Information System (INIS)

    Yang, Xu; Cao, Ding; Liang, Xiumei; Zhao, Jiannong

    2017-01-01

    Several studies have examined the relationships between diffusion tensor imaging (DTI)-measured fractional anisotropy (FA) and the symptoms of schizophrenia, but results vary across the studies. The aim of this study was to carry out a meta-analysis of correlation coefficients reported by relevant studies to evaluate the correlative relationships between FA of various parts of the brain and schizophrenia symptomatic assessments. Literature was searched in several electronic databases, and study selection was based on precised eligibility criteria. Correlation coefficients between FA of a part of the brain and schizophrenia symptom were first converted into Fisher's z-scores for meta-analyses, and then overall effect sizes were back transformed to correlation coefficients. Thirty-three studies (1121 schizophrenia patients; age 32.66 years [95% confidence interval (CI) 30.19, 35.13]; 65.95 % [57.63, 74.28] males) were included in this meta-analysis. Age was inversely associated with brain FA (z-scores [95% CI] -0.23 [-0.14, -0.32]; p %<0.00001). Brain FA of various areas was inversely associated with negative symptoms of schizophrenia (z-score -0.30 [-0.23, -0.36]; p %<0.00001) but was positively associated with positive symptoms of schizophrenia (z-score 0.16 [0.04, 0.27]; p = 0.007) and general psychopathology of schizophrenia (z-score 0.26 [0.15, 0.37]; p = 0.00001). Although, DTI-measured brain FA is found to be inversely associated with negative symptoms and positively associated with positive symptoms and general psychopathology of schizophrenia, the effect sizes of these correlations are low and may not be clinically significant. Moreover, brain FA was also negatively associated with age of patients. (orig.)

  16. Schizophrenia symptomatic associations with diffusion tensor imaging measured fractional anisotropy of brain: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xu [Chongqing Medical University, Department of Medical Imaging, Second Affiliated Hospital, Chongqing (China); Fifth People' s Hospital of Chongqing, Department of Medical Imaging, Chongqing (China); Cao, Ding [Chongqing Medical University, Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing (China); Liang, Xiumei [Fifth People' s Hospital of Chongqing, Department of Medical Imaging, Chongqing (China); Zhao, Jiannong [Chongqing Medical University, Department of Medical Imaging, Second Affiliated Hospital, Chongqing (China)

    2017-07-15

    Several studies have examined the relationships between diffusion tensor imaging (DTI)-measured fractional anisotropy (FA) and the symptoms of schizophrenia, but results vary across the studies. The aim of this study was to carry out a meta-analysis of correlation coefficients reported by relevant studies to evaluate the correlative relationships between FA of various parts of the brain and schizophrenia symptomatic assessments. Literature was searched in several electronic databases, and study selection was based on precised eligibility criteria. Correlation coefficients between FA of a part of the brain and schizophrenia symptom were first converted into Fisher's z-scores for meta-analyses, and then overall effect sizes were back transformed to correlation coefficients. Thirty-three studies (1121 schizophrenia patients; age 32.66 years [95% confidence interval (CI) 30.19, 35.13]; 65.95 % [57.63, 74.28] males) were included in this meta-analysis. Age was inversely associated with brain FA (z-scores [95% CI] -0.23 [-0.14, -0.32]; p %<0.00001). Brain FA of various areas was inversely associated with negative symptoms of schizophrenia (z-score -0.30 [-0.23, -0.36]; p %<0.00001) but was positively associated with positive symptoms of schizophrenia (z-score 0.16 [0.04, 0.27]; p = 0.007) and general psychopathology of schizophrenia (z-score 0.26 [0.15, 0.37]; p = 0.00001). Although, DTI-measured brain FA is found to be inversely associated with negative symptoms and positively associated with positive symptoms and general psychopathology of schizophrenia, the effect sizes of these correlations are low and may not be clinically significant. Moreover, brain FA was also negatively associated with age of patients. (orig.)

  17. Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies.

    Science.gov (United States)

    Rodríguez, Alexander J; Nunes, Vania dos Santos; Mastronardi, Claudio A; Neeman, Teresa; Paz-Filho, Gilberto J

    2016-03-01

    The adipocytokines leptin and adiponectin have been variously associated with diabetic microvascular complications. No comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications. This is a systematic review of cross-sectional studies comparing circulating adipocytokines in patients with type 2 diabetes mellitus (T2DM), with and without microvascular complications. Studies were retrieved from MEDLINE, EMBASE, Scopus and Cochrane databases. Study quality was evaluated using a modified Newcastle-Ottawa Scale. Meta-analysis was performed using an inverse-variance model, providing standardised mean differences (SMD) and 95% confidence intervals (CI). Heterogeneity was determined by I(2) statistic. Amongst 554 identified studies, 28 were included in the review. Study quality range was 3.5-9 (maximum 11). Higher leptin levels were associated with microalbuminuria (SMD=0.41; 95% CI=0.14-0.67; n=901; p=0.0003), macroalbuminuria (SMD=0.68; 95% CI=0.30-1.06; n=406; p=0.0004), and neuropathy (SMD=0.26; 95% CI=0.07-0.44; n=609; p=0.008). Higher adiponectin levels were associated with microalbuminuria (SMD=0.55; 95% CI=0.29-0.81, n=274; p1), macroalbuminuria (SMD=1.37; 95% CI=0.78-1.97, n=246; p1), neuropathy (SMD=0.25; 95% CI=0.14-0.36; n=1516; p1), and retinopathy (SMD=0.38; 95% CI=0.25-0.51; n=1306; p1). Meta-regression suggested no influence of body mass index and duration of diabetes on effect size, and a weak trend in terms of age on effect size. Our meta-analysis suggests leptin and adiponectin levels are higher in T2DM patients with microvascular complications. Studies were limited by cross-sectional design. Large prospective analyses are required to validate these findings. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Allison L Weber

    Full Text Available Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress.We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genome-wide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67-79% and 56-66% of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis.We identified novel candidate genes associated with variation in resistance to oxidative stress that have context-dependent effects. These results form the basis for future translational studies to identify oxidative stress susceptibility/resistance genes that are evolutionary conserved and might play a role in human disease.

  19. Neurotransmitter systems and neurotrophic factors in autism: association study of 37 genes suggests involvement of DDC.

    Science.gov (United States)

    Toma, Claudio; Hervás, Amaia; Balmaña, Noemí; Salgado, Marta; Maristany, Marta; Vilella, Elisabet; Aguilera, Francisco; Orejuela, Carmen; Cuscó, Ivon; Gallastegui, Fátima; Pérez-Jurado, Luis Alberto; Caballero-Andaluz, Rafaela; Diego-Otero, Yolanda de; Guzmán-Alvarez, Guadalupe; Ramos-Quiroga, Josep Antoni; Ribasés, Marta; Bayés, Mònica; Cormand, Bru

    2013-09-01

    Neurotransmitter systems and neurotrophic factors can be considered strong candidates for autism spectrum disorder (ASD). The serotoninergic and dopaminergic systems are involved in neurotransmission, brain maturation and cortical organization, while neurotrophic factors (NTFs) participate in neurodevelopment, neuronal survival and synapses formation. We aimed to test the contribution of these candidate pathways to autism through a case-control association study of genes selected both for their role in central nervous system functions and for pathophysiological evidences. The study sample consisted of 326 unrelated autistic patients and 350 gender-matched controls from Spain. We genotyped 369 tagSNPs to perform a case-control association study of 37 candidate genes. A significant association was obtained between the DDC gene and autism in the single-marker analysis (rs6592961, P = 0.00047). Haplotype-based analysis pinpointed a four-marker combination in this gene associated with the disorder (rs2329340C-rs2044859T-rs6592961A-rs11761683T, P = 4.988e-05). No significant results were obtained for the remaining genes after applying multiple testing corrections. However, the rs167771 marker in DRD3, associated with ASD in a previous study, displayed a nominal association in our analysis (P = 0.023). Our data suggest that common allelic variants in the DDC gene may be involved in autism susceptibility.

  20. Epigenome-wide association study of metabolic syndrome in African-American adults.

    Science.gov (United States)

    Akinyemiju, Tomi; Do, Anh N; Patki, Amit; Aslibekyan, Stella; Zhi, Degui; Hidalgo, Bertha; Tiwari, Hemant K; Absher, Devin; Geng, Xin; Arnett, Donna K; Irvin, Marguerite R

    2018-01-01

    The high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies. Data on metabolic syndrome and DNA methylation was assessed on 614 African-Americans from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the joint harmonized criteria, and DNA methylation was assessed using the Illumina HumanMethylation450K Bead Chip assay on DNA extracted from buffy coat. Linear mixed effects regression models were used to examine the association between CpG methylation at > 450,000 CpG sites and metabolic syndrome adjusted for study covariates. Replication using DNA from a separate sample of 69 African-Americans, as well as meta-analysis combining both cohorts, was conducted. Two differentially methylated CpG sites in the IGF2BP1 gene on chromosome 17 (cg06638433; p value = 3.10 × 10 - 7 ) and the ABCG1 gene on chromosome 21 (cg06500161; p value = 2.60 × 10 - 8 ) were identified. Results for the ABCG1 gene remained statistically significant in the replication dataset and meta-analysis. Metabolic syndrome was consistently associated with increased methylation in the ABCG1 gene in the discovery and replication datasets, a gene that encodes a protein in the ATP-binding cassette transporter family and is involved in intra- and extra-cellular signaling and lipid transport.

  1. Association between anxiety and severe quality-of-life impairment in postmenopausal women: analysis of a multicenter Latin American cross-sectional study.

    Science.gov (United States)

    Núñez-Pizarro, Jorge L; González-Luna, Alejandro; Mezones-Holguín, Edward; Blümel, Juan E; Barón, Germán; Bencosme, Ascanio; Benítez, Zully; Bravo, Luz M; Calle, Andrés; Flores, Daniel; Espinoza, María T; Gómez, Gustavo; Hernández-Bueno, José A; Martino, Mabel; Lima, Selva; Monterrosa, Alvaro; Mostajo, Desiree; Ojeda, Eliana; Onatra, William; Sánchez, Hugo; Tserotas, Konstantinos; Vallejo, María S; Witis, Silvina; Zúñiga, María C; Chedraui, Peter

    2017-06-01

    To evaluate associations between anxiety and severe impairment of quality of life (QoL) in Latin American postmenopausal women. This was a secondary analysis of a multicenter cross-sectional study among postmenopausal women aged 40 to 59 from 11 Latin American countries. We evaluated anxiety (The Goldberg Depression and Anxiety Scale), and QoL (Menopause Rating Scale [MRS]), and included sociodemographic, clinical, lifestyle, and anthropometric variables in the analysis. Poisson family generalized linear models with robust standard errors were used to estimate prevalence ratios (PRs) and 95% CIs. There were two adjusted models: a statistical model that included variables associated with the outcomes in bivariate analyses, and an epidemiologic model that included potentially confounding variables from literature review. Data from 3,503 women were included; 61.9% had anxiety (Goldberg). Severe QoL impairment (total MRS score ≥17) was present in 13.7% of women, as well as severe symptoms (MRS subscales): urogenital (25.5%), psychological (18.5%), and somatic (4.5%). Anxiety was independently associated with severe QoL impairment and severe symptoms in the epidemiological (MRS total score: PR 3.6, 95% CI, 2.6-5.0; somatic: 5.1, 95% CI, 2.6-10.1; psychological: 2.8, 95% CI, 2.2-3.6; and urogenital: 1.4, 95% CI, 1.2-1.6) and the statistical model (MRS total score: PR 3.5, 95% CI, 2.6-4.9; somatic: 5.0, 95% CI, 2.5-9.9; psychological: 2.9, 95% CI, 2.2-3.7; and urogenital: 1.4; 95% CI, 1.2-1.6). In this postmenopausal Latin American sample, anxiety was independently associated with severe QoL impairment. Hence, screening for anxiety in this population is important.

  2. Use of meta-analysis to combine candidate gene association studies: application to study the relationship between the ESR PvuII polymorphism and sow litter size

    Directory of Open Access Journals (Sweden)

    Alfonso Leopoldo

    2005-07-01

    Full Text Available Abstract This article investigates the application of meta-analysis on livestock candidate gene effects. The PvuII polymorphism of the ESR gene is used as an example. The association among ESR PvuII alleles with the number of piglets born alive and total born in the first (NBA1, TNB1 and later parities (NBA, TNB is reviewed by conducting a meta-analysis of 15 published studies including 9329 sows. Under a fixed effects model, litter size values were significantly lower in the "AA" genotype groups when compared with "AB" and "BB" homozygotes. Under the random effects model, the results were similar although differences between "AA" and "AB" genotype groups were not clearly significant for NBA and TNB. Nevertheless, the most noticeable result was the high and significant heterogeneity estimated among studies. This heterogeneity could be assigned to error sampling, genotype by environment interaction, linkage or epistasis, as referred to in the literature, but also to the hypothesis of population admixture/stratification. It is concluded that meta-analysis can be considered as a helpful analytical tool to synthesise and discuss livestock candidate gene effects. The main difficulty found was the insufficient information on the standard errors of the estimated genotype effects in several publications. Consequently, the convenience of publishing the standard errors or the concrete P-values instead of the test significance level should be recommended to guarantee the quality of candidate gene effect meta-analyses.

  3. The association between ATM IVS 22-77 T>C and cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Lin Zhao

    Full Text Available BACKGROUND AND OBJECTIVES: It has become increasingly clear that ATM (ataxia-telangiectasia-mutated safeguards genome stability, which is a cornerstone of cellular homeostasis, and ATM IVS 22-77 T>C affects the normal activity of ATM proteins. However, the association between the ATM IVS 22-77 T>C genetic variant and cancer risk is controversial. Therefore, we conducted a systematic meta-analysis to estimate the overall cancer risk associated with the polymorphism and to quantify any potential between-study heterogeneity. METHODS: A total of nine studies including 4,470 cases and 4,862 controls were analyzed for ATM IVS 22-77 T>C association with cancer risk in this meta-analysis. Heterogeneity among articles and their publication bias were also tested. RESULTS: Our results showed that no association reached the level of statistical significance in the overall risk. Interestingly, in the stratified analyses, we observed an inverse relationship in lung and breast cancer. CONCLUSION: Further functional research on the ATM mechanism should be performed to explain the inconsistent results in different cancer types.

  4. The association between post-traumatic stress disorder and shorter telomere length: A systematic review and meta-analysis.

    Science.gov (United States)

    Li, Xuemei; Wang, Jiang; Zhou, Jianghua; Huang, Pan; Li, Jiping

    2017-08-15

    Post-traumatic stress disorder (PTSD) is a common psychiatric disorder, which may accelerate aging. Many study have investigated the association between telomeres length and PTSD, but results from published studies are contradictory. Therefore, Meta-analysis approaches were conducted to give more precise estimate of relationship between telomere length and PTSD. We systematically reviewed the databases of PUBMED, PsycINFO, Medline(Ovid SP) and EMBASE for all articles on the association between telomere length and PTSD. Data were summarized by using random-effects in the meta-analysis. The heterogeneity among studies were examined by using Cochrane's Q statistic and I-squared. Five eligible studies containing 3851 participants were included in our meta-analysis. Shorten telomere length was significantly associated with PTSD with mean difference of -0.19( 95% CI: -0.27, -0.01; P<0.001) with I-square of 96%. The results from subgroup analysis demonstrated that shorter telomere length was significantly associated with PTSD across all gender groups, with mean difference of -0.15( 95% CI: -0.29, -0.01; P=0.04) for female, mean difference of -0.17( 95% CI: -0.19, -0.15; P<0.001) for male. Meanwhile, shorten telomere length was significantly associated with sexual assault(mean difference =-0.15, 95% CI: -0.29, -0.01), childhood trauma (mean difference =-0.08, 95% CI: -0.19, -0.07), but not combat (mean difference =-0.39, 95% CI: -0.83, 0.05). Compared to the individuals without PTSD, individuals with PTSD have shorter telomere length, which has implications for early intervention and timely treatment to prevent future adverse health outcomes. Copyright © 2017. Published by Elsevier B.V.

  5. The association between obesity and dengue severity among pediatric patients: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Mohd Syis Zulkipli

    2018-02-01

    Full Text Available Severe dengue infection often has unpredictable clinical progressions and outcomes. Obesity may play a role in the deterioration of dengue infection due to stronger body immune responses. Several studies found that obese dengue patients have a more severe presentation with a poorer prognosis. However, the association was inconclusive due to the variation in the results of earlier studies. Therefore, we conducted a systematic review and meta-analysis to explore the relationship between obesity and dengue severity.We performed a systematic search of relevant studies on Ovid (MEDLINE, EMBASE, the Cochrane Library, Web of Science, Scopus and grey literature databases. At least two authors independently conducted the literature search, selecting eligible studies, and extracting data. Meta-analysis using random-effects model was conducted to compute the pooled odds ratio with 95% confidence intervals (CI.We obtained a total of 13,333 articles from the searches. For the final analysis, we included a total of fifteen studies among pediatric patients. Three cohort studies, two case-control studies, and one cross-sectional study found an association between obesity and dengue severity. In contrast, six cohort studies and three case-control studies found no significant relationship between obesity and dengue severity. Our meta-analysis revealed that there was 38 percent higher odds (Odds Ratio = 1.38; 95% CI:1.10, 1.73 of developing severe dengue infection among obese children compared to non-obese children. We found no heterogeneity found between studies. The differences in obesity classification, study quality, and study design do not modify the association between obesity and dengue severity.This review found that obesity is a risk factor for dengue severity among children. The result highlights and improves our understanding that obesity might influence the severity of dengue infection.

  6. The association between obesity and dengue severity among pediatric patients: A systematic review and meta-analysis

    Science.gov (United States)

    Dahlui, Maznah; Jamil, Nor’ashikin; Peramalah, Devi; Wai, Hoe Victor Chee; Bulgiba, Awang; Rampal, Sanjay

    2018-01-01

    Background Severe dengue infection often has unpredictable clinical progressions and outcomes. Obesity may play a role in the deterioration of dengue infection due to stronger body immune responses. Several studies found that obese dengue patients have a more severe presentation with a poorer prognosis. However, the association was inconclusive due to the variation in the results of earlier studies. Therefore, we conducted a systematic review and meta-analysis to explore the relationship between obesity and dengue severity. Methods We performed a systematic search of relevant studies on Ovid (MEDLINE), EMBASE, the Cochrane Library, Web of Science, Scopus and grey literature databases. At least two authors independently conducted the literature search, selecting eligible studies, and extracting data. Meta-analysis using random-effects model was conducted to compute the pooled odds ratio with 95% confidence intervals (CI). Findings We obtained a total of 13,333 articles from the searches. For the final analysis, we included a total of fifteen studies among pediatric patients. Three cohort studies, two case-control studies, and one cross-sectional study found an association between obesity and dengue severity. In contrast, six cohort studies and three case-control studies found no significant relationship between obesity and dengue severity. Our meta-analysis revealed that there was 38 percent higher odds (Odds Ratio = 1.38; 95% CI:1.10, 1.73) of developing severe dengue infection among obese children compared to non-obese children. We found no heterogeneity found between studies. The differences in obesity classification, study quality, and study design do not modify the association between obesity and dengue severity. Conclusion This review found that obesity is a risk factor for dengue severity among children. The result highlights and improves our understanding that obesity might influence the severity of dengue infection. PMID:29415036

  7. Association between interleukin 1 receptor antagonist gene 86-bp VNTR polymorphism and sepsis: a meta-analysis.

    Science.gov (United States)

    Fang, Fang; Pan, Jian; Li, Yiping; Xu, Lixiao; Su, Guanghao; Li, Gang; Wang, Jian

    2015-01-01

    Many studies have focused on the relationship between interleukin 1 receptor antagonist (IL1RN) gene 86-bp VNTR polymorphism and sepsis, but the results remain inconsistent. Thus, a meta-analysis was carried out to derive a more precise estimation of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Relevant publications were searched in several widely used databases and six eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Significant associations between IL1RN 86-bp VNTR polymorphism and sepsis risk were observed in both overall meta-analysis for L2 versus 22 (OR=0.75, 95% CI=0.59-0.94) and severe sepsis subgroup for LL+L2 versus 22 (OR=0.67, 95% CI=0.47-0.93). L stands for long alleles containing three to six repeats; 2 stands for short allele containing two repeats. However, no significant sepsis mortality variation was detected for all genetic models. According to the results of our meta-analysis, the IL1RN 86-bp VNTR polymorphism probably associates with sepsis risk but not with sepsis-related mortality. Copyright © 2014. Published by Elsevier Inc.

  8. SimHap GUI: an intuitive graphical user interface for genetic association analysis.

    Science.gov (United States)

    Carter, Kim W; McCaskie, Pamela A; Palmer, Lyle J

    2008-12-25

    Researchers wishing to conduct genetic association analysis involving single nucleotide polymorphisms (SNPs) or haplotypes are often confronted with the lack of user-friendly graphical analysis tools, requiring sophisticated statistical and informatics expertise to perform relatively straightforward tasks. Tools, such as the SimHap package for the R statistics language, provide the necessary statistical operations to conduct sophisticated genetic analysis, but lacks a graphical user interface that allows anyone but a professional statistician to effectively utilise the tool. We have developed SimHap GUI, a cross-platform integrated graphical analysis tool for conducting epidemiological, single SNP and haplotype-based association analysis. SimHap GUI features a novel workflow interface that guides the user through each logical step of the analysis process, making it accessible to both novice and advanced users. This tool provides a seamless interface to the SimHap R package, while providing enhanced functionality such as sophisticated data checking, automated data conversion, and real-time estimations of haplotype simulation progress. SimHap GUI provides a novel, easy-to-use, cross-platform solution for conducting a range of genetic and non-genetic association analyses. This provides a free alternative to commercial statistics packages that is specifically designed for genetic association analysis.

  9. Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans.

    Science.gov (United States)

    Carty, Cara L; Keene, Keith L; Cheng, Yu-Ching; Meschia, James F; Chen, Wei-Min; Nalls, Mike; Bis, Joshua C; Kittner, Steven J; Rich, Stephen S; Tajuddin, Salman; Zonderman, Alan B; Evans, Michele K; Langefeld, Carl D; Gottesman, Rebecca; Mosley, Thomas H; Shahar, Eyal; Woo, Daniel; Yaffe, Kristine; Liu, Yongmei; Sale, Michèle M; Dichgans, Martin; Malik, Rainer; Longstreth, W T; Mitchell, Braxton D; Psaty, Bruce M; Kooperberg, Charles; Reiner, Alexander; Worrall, Bradford B; Fornage, Myriam

    2015-08-01

    The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with Pstroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613; P=3.9×10(-8)) in African Americans. Nominal associations (Pstroke were observed for 18 variants in or near genes implicated in cell cycle/mRNA presplicing (PTPRG, CDC5L), platelet function (HPS4), blood-brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, and IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B, and ZFHX3) were nominally associated (Pstroke in COMPASS. We identified a novel genetic variant associated with total stroke in African Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations. © 2015 American Heart Association, Inc.

  10. Association between the European GWAS-identified susceptibility locus at chromosome 4p16 and the risk of atrial septal defect: a case-control study in Southwest China and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Li Zhao

    Full Text Available Atrial septal defect (ASD is the third most frequent type of congenital heart anomaly, featuring shunting of blood between the two atria. Gene-environment interaction remains to be an acknowledged cause for ASD occurrence. A recent European genome-wide association study (GWAS of congenital heart disease (CHD identified 3 susceptibility SNPs at chromosome 4p16 associated with ASD: rs870142, rs16835979 and rs6824295. A Chinese-GWAS of CHD conducted in the corresponding period did not reveal the 3 susceptibility SNPs, but reported 2 different risk SNPs: rs2474937 and rs1531070. Therefore, we aimed to investigate the associations between the 3 European GWAS-identified susceptibility SNPs and ASD risk in the Han population in southwest China. Additionally, to increase the robustness of our current analysis, we conducted a meta-analysis combining published studies and our current case-control study. We performed association, linkage disequilibrium, and haplotype analysis among the 3 SNPs in 190 ASD cases and 225 age-, sex-, and ethnicity-matched healthy controls. Genotype and allele frequencies among the 3 SNPs showed statistically significant differences between the cases and controls. Our study found that individuals carrying the allele T of rs870142, the allele A of rs16835979, and the allele T of rs6824295 had a respective 50.1% (odds ratio (OR = 1.501, 95% confidence interval (CI = 1.122-2.009, PFDR-BH = 0.018, 48.5% (OR = 1.485, 95%CI = 1.109-1.987, PFDR-BH = 0.012, and 38.6% (OR = 1.386, 95%CI = 1.042-1.844, PFDR-BH = 0.025 increased risk to develop ASD than wild-type allele carriers in our study cohort. In the haplotype analysis, we identified a disease-risk haplotype (TAT (OR = 1.540, 95%CI = 1.030-2.380, PFDR-BH = 0.016. Our meta-analysis also showed that the investigated SNP was associated with ASD risk (combined OR (95%CI = 1.35 (1.24-1.46, P < 0.00001. Our study provides compelling evidence to motivate better understanding of the etiology

  11. gsSKAT: Rapid gene set analysis and multiple testing correction for rare-variant association studies using weighted linear kernels.

    Science.gov (United States)

    Larson, Nicholas B; McDonnell, Shannon; Cannon Albright, Lisa; Teerlink, Craig; Stanford, Janet; Ostrander, Elaine A; Isaacs, William B; Xu, Jianfeng; Cooney, Kathleen A; Lange, Ethan; Schleutker, Johanna; Carpten, John D; Powell, Isaac; Bailey-Wilson, Joan E; Cussenot, Olivier; Cancel-Tassin, Geraldine; Giles, Graham G; MacInnis, Robert J; Maier, Christiane; Whittemore, Alice S; Hsieh, Chih-Lin; Wiklund, Fredrik; Catalona, William J; Foulkes, William; Mandal, Diptasri; Eeles, Rosalind; Kote-Jarai, Zsofia; Ackerman, Michael J; Olson, Timothy M; Klein, Christopher J; Thibodeau, Stephen N; Schaid, Daniel J

    2017-05-01

    Next-generation sequencing technologies have afforded unprecedented characterization of low-frequency and rare genetic variation. Due to low power for single-variant testing, aggregative methods are commonly used to combine observed rare variation within a single gene. Causal variation may also aggregate across multiple genes within relevant biomolecular pathways. Kernel-machine regression and adaptive testing methods for aggregative rare-variant association testing have been demonstrated to be powerful approaches for pathway-level analysis, although these methods tend to be computationally intensive at high-variant dimensionality and require access to complete data. An additional analytical issue in scans of large pathway definition sets is multiple testing correction. Gene set definitions may exhibit substantial genic overlap, and the impact of the resultant correlation in test statistics on Type I error rate control for large agnostic gene set scans has not been fully explored. Herein, we first outline a statistical strategy for aggregative rare-variant analysis using component gene-level linear kernel score test summary statistics as well as derive simple estimators of the effective number of tests for family-wise error rate control. We then conduct extensive simulation studies to characterize the behavior of our approach relative to direct application of kernel and adaptive methods under a variety of conditions. We also apply our method to two case-control studies, respectively, evaluating rare variation in hereditary prostate cancer and schizophrenia. Finally, we provide open-source R code for public use to facilitate easy application of our methods to existing rare-variant analysis results. © 2017 WILEY PERIODICALS, INC.

  12. Multi-element analysis of emeralds and associated rocks by k{sub 0} neutron activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Acharya, R.N.; Mondal, R.K.; Burte, P.P.; Nair, A.G.C.; Reddy, N.B.Y.; Reddy, L.K.; Reddy, A.V.R.; Manohar, S.B

    2000-12-15

    Multi-element analysis was carried out in natural emeralds, their associated rocks and one sample of beryl obtained from Rajasthan, India. The concentrations of 21 elements were assayed by Instrumental Neutron Activation Analysis using the k{sub 0} method (k{sub 0} INAA method) and high-resolution gamma ray spectrometry. The data reveal the segregation of some elements from associated (trapped and host) rocks to the mineral beryl forming the gemstones. A reference rock standard of the US Geological Survey (USGS BCR-1) was also analysed as a control of the method.

  13. Multi-omics analysis provides insight to the Ignicoccus hospitalis-Nanoarchaeum equitans association.

    Science.gov (United States)

    Rawle, Rachel A; Hamerly, Timothy; Tripet, Brian P; Giannone, Richard J; Wurch, Louie; Hettich, Robert L; Podar, Mircea; Copié, Valerie; Bothner, Brian

    2017-09-01

    Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted 'omics' analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized using interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis-N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. This multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis-N. equitans association. Our study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Data-flow Analysis of Programs with Associative Arrays

    Directory of Open Access Journals (Sweden)

    David Hauzar

    2014-05-01

    Full Text Available Dynamic programming languages, such as PHP, JavaScript, and Python, provide built-in data structures including associative arrays and objects with similar semantics—object properties can be created at run-time and accessed via arbitrary expressions. While a high level of security and safety of applications written in these languages can be of a particular importance (consider a web application storing sensitive data and providing its functionality worldwide, dynamic data structures pose significant challenges for data-flow analysis making traditional static verification methods both unsound and imprecise. In this paper, we propose a sound and precise approach for value and points-to analysis of programs with associative arrays-like data structures, upon which data-flow analyses can be built. We implemented our approach in a web-application domain—in an analyzer of PHP code.

  15. Depression and risk of fracture and bone loss: an updated meta-analysis of prospective studies.

    Science.gov (United States)

    Wu, Q; Liu, B; Tonmoy, S

    2018-03-12

    This meta-analysis pooled results from 23 qualifying individual cohort studies and found that depression was significantly associated with an increased risk of fractures and bone loss. The association between depression and risk of fracture remains controversial. We conducted a comprehensive meta-analysis to examine the effect of depression on the risk of osteoporotic fractures and bone loss. We searched databases and reviewed citations in relevant articles for eligible cohort studies. Two investigators independently conducted study selection, appraisal, and data abstraction through the use of a standardized protocol. Random effect models were used for meta-analysis. Cochrane Q and I 2 statistics were used to assess heterogeneity. Funnel plots and rank correlation tests were used to evaluate publication bias. Twenty-three studies were included for meta-analysis. In studies that reported hazard ratio (HR) as the outcome (nine studies [n = 309,862]), depression was associated with 26% increase in fracture risk (HR = 1.26, 95% CI, 1.10-1.43, p meta-analysis having modified inclusion criteria and in different subgroup analyses as well. Significant heterogeneity was observed in the meta-analysis; however, no significant publication bias was detected. Depression is associated with a significant increased risk in fracture and bone loss. Effective prevention may decrease such risk.

  16. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    NARCIS (Netherlands)

    K. Michailidou (Kyriaki); J. Beesley (Jonathan); S. Lindstrom (Stephen); S. Canisius (Sander); J. Dennis (Joe); M. Lush (Michael); M. Maranian (Melanie); M.K. Bolla (Manjeet); Q. Wang (Qing); M. Shah (Mitul); B. Perkins (Barbara); K. Czene (Kamila); M. Eriksson (Mikael); H. Darabi (Hatef); J.S. Brand (Judith S.); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); H. Flyger (Henrik); S.F. Nielsen (Sune); N. Rahman (Nazneen); C. Turnbull (Clare); O. Fletcher (Olivia); J. Peto (Julian); L.J. Gibson (Lorna); I. dos Santos Silva (Isabel); J. Chang-Claude (Jenny); D. Flesch-Janys (Dieter); A. Rudolph (Anja); U. Eilber (Ursula); T.W. Behrens (Timothy); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); S. Khan (Sofia); K. Aaltonen (Kirsimari); H. Ahsan (Habibul); M.G. Kibriya (Muhammad); A.S. Whittemore (Alice S.); E.M. John (Esther M.); K.E. Malone (Kathleen E.); M.D. Gammon (Marilie); R.M. Santella (Regina M.); G. Ursin (Giske); E. Makalic (Enes); D.F. Schmidt (Daniel); G. Casey (Graham); D.J. Hunter (David J.); S.M. Gapstur (Susan M.); M.M. Gaudet (Mia); W.R. Diver (Ryan); C.A. Haiman (Christopher A.); F.R. Schumacher (Fredrick); B.E. Henderson (Brian); L. Le Marchand (Loic); C.D. Berg (Christine); S.J. Chanock (Stephen); J.D. Figueroa (Jonine); R.N. Hoover (Robert N.); D. Lambrechts (Diether); P. Neven (Patrick); H. Wildiers (Hans); E. van Limbergen (Erik); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; S. Cornelissen (Sten); F.J. Couch (Fergus); J.E. Olson (Janet); B. Hallberg (Boubou); C. Vachon (Celine); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); M.A. Adank (Muriel); R.B. van der Luijt (Rob); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); D. Kang (Daehee); J.-Y. Choi (Ji-Yeob); S.K. Park (Sue K.); K.Y. Yoo; K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hiroji); K. Tajima (Kazuo); P. Guénel (Pascal); T. Truong (Thérèse); C. Mulot (Claire); M. Sanchez (Marie); B. Burwinkel (Barbara); F. Marme (Federick); H. Surowy (Harald); C. Sohn (Christof); A.H. Wu (Anna H); C.-C. Tseng (Chiu-chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); A. González-Neira (Anna); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y. Gao; H. Cai (Hui); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.-M. Mulligan (Anna-Marie); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); A. Lindblom (Annika); S. Margolin (Sara); S.H. Teo (Soo Hwang); C.H. Yip (Cheng Har); N.A.M. Taib (Nur Aishah Mohd); G.-H. Tan (Gie-Hooi); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John); J.M. Collée (Margriet); W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); J. Hopper (John); M.C. Southey (Melissa); H. Tsimiklis (Helen); C. Apicella (Carmel); C-Y. Shen (Chen-Yang); C.-N. Hsiung (Chia-Ni); P.-E. Wu (Pei-Ei); M.-F. Hou (Ming-Feng); V. Kristensen (Vessela); S. Nord (Silje); G.G. Alnæs (Grethe); G.G. Giles (Graham G.); R.L. Milne (Roger); C.A. McLean (Catriona Ann); F. Canzian (Federico); D. Trichopoulos (Dimitrios); P.H.M. Peeters; E. Lund (Eiliv); R. Sund (Reijo); K.T. Khaw; M.J. Gunter (Marc J.); D. Palli (Domenico); L.M. Mortensen (Lotte Maxild); L. Dossus (Laure); J.-M. Huerta (Jose-Maria); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); K. Muir (Kenneth); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); J.M. Hartman (Joost); X. Miao; K.S. Chia (Kee Seng); C.W. Chan (Ching Wan); P.A. Fasching (Peter); R. Hein (Rebecca); M.W. Beckmann (Matthias); L. Haeberle (Lothar); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); A.J. Swerdlow (Anthony ); L.A. Brinton (Louise); M. García-Closas (Montserrat); W. Zheng (Wei); S.L. Halverson (Sandra L.); M. Shrubsole (Martha); J. Long (Jirong); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); H. Brauch (Hiltrud); U. Hamann (Ute); T. Brüning (Thomas); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); L. Bernard (Loris); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); T. Huzarski (Tomasz); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); S. Slager (Susan); A.E. Toland (Amanda); C.B. Ambrosone (Christine); D. Yannoukakos (Drakoulis); M. Kabisch (Maria); D. Torres (Diana); S.L. Neuhausen (Susan); H. Anton-Culver (Hoda); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); S. Healey (Sue); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); G. Pita (Guillermo); M.R. Alonso (Rosario); N. Álvarez (Nuria); D. Herrero (Daniel); J. Simard (Jacques); P.P.D.P. Pharoah (Paul P.D.P.); P. Kraft (Peter); A.M. Dunning (Alison); G. Chenevix-Trench (Georgia); P. Hall (Per); D.F. Easton (Douglas)

    2015-01-01

    textabstractGenome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS,

  17. Association between structural and functional brain alterations in drug-free patients with schizophrenia: a multimodal meta-analysis.

    Science.gov (United States)

    Gao, Xin; Zhang, Wenjing; Yao, Li; Xiao, Yuan; Liu, Lu; Liu, Jieke; Li, Siyi; Tao, Bo; Shah, Chandan; Gong, Qiyong; Sweeney, John A; Lui, Su

    2018-03-01

    Neuroimaging studies have shown both structural and functional abnormalities in patients with schizophrenia. Recently, studies have begun to explore the association between structural and functional grey matter abnormalities. By conducting a meta-analysis on morphometric and functional imaging studies of grey matter alterations in drug-free patients, the present study aims to examine the degree of overlap between brain regions with anatomic and functional changes in patients with schizophrenia. We performed a systematic search of PubMed, Embase, Web of Science and the Cochrane Library to identify relevant publications. A multimodal analysis was then conducted using Seed-based d Mapping software. Exploratory analyses included jackknife, subgroup and meta-regression analyses. We included 15 structural MRI studies comprising 486 drug-free patients and 485 healthy controls, and 16 functional MRI studies comprising 403 drug-free patients and 428 controls in our meta-analysis. Drug-free patients were examined to reduce pharmacological effects on the imaging data. Multimodal analysis showed considerable overlap between anatomic and functional changes, mainly in frontotemporal regions, bilateral medial posterior cingulate/paracingulate gyrus, bilateral insula, basal ganglia and left cerebellum. There were also brain regions showing only anatomic changes in the right superior frontal gyrus, left supramarginal gyrus, right lingual gyrus and functional alternations involving the right angular gyrus. The methodological aspects, patient characteristics and clinical variables of the included studies were heterogeneous, and we cannot exclude medication effects. The present study showed overlapping anatomic and functional brain abnormalities mainly in the default mode (DMN) and auditory networks (AN) in drug-free patients with schizophrenia. However, the pattern of changes differed in these networks. Decreased grey matter was associated with decreased activation within the DMN

  18. A meta-analysis of the association of STAT4 polymorphism with systemic lupus erythematosus.

    Science.gov (United States)

    Yuan, Hui; Feng, Jin-Bao; Pan, Hai-Feng; Qiu, Li-Xin; Li, Lian-Hong; Zhang, Ning; Ye, Dong-Qing

    2010-06-01

    STAT4 has been newly identified as a susceptibility gene for systemic lupus erythematosus (SLE) in recent reports. To more precisely estimate the association between STAT4 polymorphism and SLE risk, a meta-analysis was performed. Studies on the association of STAT4 rs7574865 or rs7601754 with SLE were fully considered and carefully selected using three electronic databases (PubMed, Embase, and Web of Science). A total of 17 comparisons from 8 relevant studies involving 7,381 patients and 11,431 controls were included to analyze the association between STAT4 rs7574865 and SLE risk. The pooled OR for the minor T allele of STAT4 rs7574865 was 1.65 (95% CI 1.56-1.75, P rs7574865 with SLE susceptibility was similar in populations of European or Asian origin, although significant differences in the minor T allele frequencies were observed in the two population controls. As for rs7601754, there were five comparisons from four relevant studies involving 2,498 patients and 4,825 controls in this meta-analysis. The pooled OR for the minor C allele of STAT4 rs7601754 was 0.67 (95% CI 0.59-0.75, P rs7574865 polymorphism as a susceptibility factor for SLE in populations of European and Asian origin. Our results also suggest that STAT4 rs7601754 polymorphism might be associated with SLE risk.

  19. Association between obesity and chronic periodontitis: a cross-sectional study.

    Science.gov (United States)

    Palle, Ajay Reddy; Reddy, C M Sanjeeva Kumar; Shankar, B Shiva; Gelli, Vemsi; Sudhakar, Jaradoddi; Reddy, K Krishna Mohana

    2013-03-01

    Chronic periodontitis is multifactorial and numerous risk factors have been identified to contribute in the disease progression. Current study aimed to conduct a cross-sectional study in a population of patients with cardiovascular diseases in order to correlate the association between obesity [body mass index (BMI) and waist circumference (WC)] and periodontal disease parameters. The study was of a cross-sectional design and a total of 201 patients were examined after obtaining their informed consent. Subjects who had a history of cardiovascular diseases and under treatment were included in the study. Two indicators of obesity were used: BMI and WC. The following periodontal parameters were assessed: Probing depth, clinical attachment level. The oral hygiene status of the subjects was assessed by the oral hygiene index (OHI, simplified) given by John C Greene and Jack R Vermillion. The influence of the BMI and other confounding variables on periodontitis severity was assessed by multivariate logistic regression analysis. Data were analyzed using SPSS. Significant association was seen with low density lipoproteins (LDL) and severity of periodontitis (p < 0.005), triglyceride levels (TGL) and severity of periodontitis (p < 0.005), cholesterol and severity of periodontitis (p < 0.005), BMI and severity of periodontitis (p < 0.001), OHI and severity of periodontitis (p < 0.001). Significant association was seen with smoking and severity of periodontitis (p < 0.005), BMI and severity of periodontitis (p < 0.001), WC and severity of periodontitis (p < 0.001), cholesterol and severity of periodontitis (p < 0.001), OHI and severity of periodontitis (p < 0.001). Obesity has been implicated as a risk factor for several conditions including cardiovascular disease, diabetes, etc. In our study the relation between measures of overall and abdominal obesity (BMI and WC) and periodontal disease showed significant association in the multivariate logistic regression analysis

  20. Transcriptional analysis of phloem-associated cells of potato.

    Science.gov (United States)

    Lin, Tian; Lashbrook, Coralie C; Cho, Sung Ki; Butler, Nathaniel M; Sharma, Pooja; Muppirala, Usha; Severin, Andrew J; Hannapel, David J

    2015-09-03

    Numerous signal molecules, including proteins and mRNAs, are transported through the architecture of plants via the vascular system. As the connection between leaves and other organs, the petiole and stem are especially important in their transport function, which is carried out by the phloem and xylem, especially by the sieve elements in the phloem system. The phloem is an important conduit for transporting photosynthate and signal molecules like metabolites, proteins, small RNAs, and full-length mRNAs. Phloem sap has been used as an unadulterated source to profile phloem proteins and RNAs, but unfortunately, pure phloem sap cannot be obtained in most plant species. Here we make use of laser capture microdissection (LCM) and RNA-seq for an in-depth transcriptional profile of phloem-associated cells of both petioles and stems of potato. To expedite our analysis, we have taken advantage of the potato genome that has recently been fully sequenced and annotated. Out of the 27 k transcripts assembled that we identified, approximately 15 k were present in phloem-associated cells of petiole and stem with greater than ten reads. Among these genes, roughly 10 k are affected by photoperiod. Several RNAs from this day length-regulated group are also abundant in phloem cells of petioles and encode for proteins involved in signaling or transcriptional control. Approximately 22 % of the transcripts in phloem cells contained at least one binding motif for Pumilio, Nova, or polypyrimidine tract-binding proteins in their downstream sequences. Highlighting the predominance of binding processes identified in the gene ontology analysis of active genes from phloem cells, 78 % of the 464 RNA-binding proteins present in the potato genome were detected in our phloem transcriptome. As a reasonable alternative when phloem sap collection is not possible, LCM can be used to isolate RNA from specific cell types, and along with RNA-seq, provides practical access to expression profiles of

  1. Association between vasectomy and risk of testicular cancer: A systematic review and meta-analysis.

    Science.gov (United States)

    Duan, Haifeng; Deng, Tuo; Chen, Yiwen; Zhao, Zhijian; Wen, Yaoan; Chen, Yeda; Li, Xiaohang; Zeng, Guohua

    2018-01-01

    A number of researchers have reported that vasectomy is a risk factor for testicular cancer. However, this conclusion is inconsistent with a number of other published articles. Hence, we conducted this meta-analysis to assess whether vasectomy increases the risk of testicular cancer. We identified all related studies by searching the PubMed, Embase, and Cochrane Library database from January 01, 1980 to June 01, 2017. The Newcastle-Ottawa Scale (NOS) checklist was used to assess all included non-randomized studies. Summarized odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the difference in outcomes between case and control groups. Subgroup analyses were performed according to the study design and country. A total of eight studies (2176 testicular cancer patients) were included in this systematic review and meta-analysis. Six articles were case-control studies, and two were cohort studies. The pooled estimate of the OR was 1.10 (95% CI: 0.93-1.30) based on the eight studies in a fixed effects model. Two subgroup analyses were performed according to the study design and country. The results were consistent with the overall findings. Publication bias was detected by Begg's test and Egger's test and p values > 0.05, respectively. Our meta-analysis suggested that there was no association between vasectomy and the development of testicular cancer. More high-quality studies are warranted to further explore the association between vasectomy and risk of testicular cancer.

  2. Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

    Directory of Open Access Journals (Sweden)

    Kshitij Srivastava

    Full Text Available MicroRNAs (miRNAs are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs. Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444 and cancer risk by using a two-sided meta-analytic approach.An updated meta-analysis based on 53 independent case-control studies consisting of 27573 cancer cases and 34791 controls was performed. Odds ratio (OR and 95% confidence interval (95% CI were used to investigate the strength of the association.Overall, the pooled analysis showed that mir-196a2 rs11614913 was associated with a decreased cancer risk (OR = 0.846, P = 0.004, TT vs. CC while other miRNA SNPs showed no association with overall cancer risk. Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that there was a strong association between miR-146a rs2910164 and overall cancer risk in Caucasian population under recessive model (OR = 1.274, 95%CI = 1.096-1.481, P = 0.002. Stratified analysis by cancer type also associated mir-196a2 rs11614913 with lung and colorectal cancer at allelic and genotypic level.The present meta-analysis suggests an important role of mir-196a2 rs11614913 polymorphism with overall cancer risk especially in Asian population. Further studies with large sample size are needed to evaluate and confirm this association.

  3. Association between serum CA 19-9 and metabolic syndrome: A cross-sectional study.

    Science.gov (United States)

    Du, Rui; Cheng, Di; Lin, Lin; Sun, Jichao; Peng, Kui; Xu, Yu; Xu, Min; Chen, Yuhong; Bi, Yufang; Wang, Weiqing; Lu, Jieli; Ning, Guang

    2017-11-01

    Increasing evidence suggests that serum CA 19-9 is associated with abnormal glucose metabolism. However, data on the association between CA 19-9 and metabolic syndrome is limited. The aim of the present study was to investigate the association between serum CA 19-9 and metabolic syndrome. A cross-sectional study was conducted on 3641 participants aged ≥40 years from the Songnan Community, Baoshan District in Shanghai, China. Logistic regression analysis was used to evaluate the association between serum CA 19-9 and metabolic syndrome. Multivariate logistic regression analysis showed that compared with participants in the first tertile of serum CA 19-9, those in the second and third tertiles had increased odds ratios (OR) for prevalent metabolic syndrome (multivariate adjusted OR 1.46 [95% confidence interval {CI} 1.11-1.92] and 1.51 [95% CI 1.14-1.98]; P trend  = 0.005). In addition, participants with elevated serum CA 19-9 (≥37 U/mL) had an increased risk of prevalent metabolic syndrome compared with those with serum CA 19-9 metabolic syndrome. In order to confirm this association and identify potential mechanisms, prospective cohort and mechanic studies should be performed. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  4. Airborne asbestos exposures associated with gasket and packing replacement: a simulation study and meta-analysis.

    Science.gov (United States)

    Madl, Amy K; Hollins, Dana M; Devlin, Kathryn D; Donovan, Ellen P; Dopart, Pamela J; Scott, Paul K; Perez, Angela L

    2014-08-01

    Exposures to airborne asbestos during the removal and installation of internal gaskets and packing associated with a valve overhaul were characterized and compared to published data according to different variables (e.g., product, equipment, task, tool, setting, duration). Personal breathing zone and area samples were collected during twelve events simulating gasket and packing replacement, clean-up and clothing handling. These samples were analyzed using PCM and TEM methods and PCM-equivalent (PCME) airborne asbestos concentrations were calculated. A meta-analysis was performed to compare these data with airborne asbestos concentrations measured in other studies involving gaskets and packing. Short-term mechanic and assistant airborne asbestos concentrations during valve work averaged 0.013f/cc and 0.008f/cc (PCME), respectively. Area samples averaged 0.008f/cc, 0.005f/cc, and 0.003f/cc (PCME) for center, bystander, and remote background, respectively. Assuming a tradesman conservatively performs 1-3 gasket and/or packing replacements daily, an average 8-h TWA was estimated to be 0.002-0.010f/cc (PCME). Combining these results in a meta-analysis of the published exposure data showed that the majority of airborne asbestos exposures during work with gaskets and packing fall within a consistent and low range. Significant differences in airborne concentrations were observed between power versus manual tools and removal versus installation tasks. Airborne asbestos concentrations resulting from gasket and packing work during a valve overhaul are consistent with historical exposure data on replacement of asbestos-containing gasket and packing materials involving multiple variables and, in nearly all plausible scenarios, result in average airborne asbestos concentrations below contemporaneous occupational exposure limits for asbestos. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    NARCIS (Netherlands)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara; Canisius, Sander; Dennis, Joe; Lush, Michael J.; Maranian, Mel J.; Bolla, Manjeet K.; Wang, Qin; Shah, Mitul; Perkins, Barbara J.; Czene, Kamila; Eriksson, Mikael; Darabi, Hatef; Brand, Judith S.; Bojesen, Stig E.; Nordestgaard, Borge G.; Flyger, Henrik; Nielsen, Sune F.; Rahman, Nazneen; Turnbull, Clare; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos-Santos-Silva, Isabel; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Eilber, Ursula; Behrens, Sabine; Nevanlinna, Heli; Muranen, Taru A.; Aittomaki, Kristiina; Blomqvist, Carl; Khan, Sofia; Aaltonen, Kirsimari; Ahsan, Habibul; Kibriya, Muhammad G.; Whittemore, Alice S.; John, Esther M.; Malone, Kathleen E.; Gammon, Marilie D.; Santella, Regina M.; Ursin, Giske; Makalic, Enes; Schmidt, Daniel F.; Casey, Graham; Hunter, David J.; Gapstur, Susan M.; Gaudet, Mia M.; Diver, W. Ryan; Haiman, Christopher A.; Schumacher, Fredrick; Henderson, Brian E.; Le Marchand, Loic; Berg, Christine D.; Chanock, Stephen J.; Figueroa, Jonine; Hoover, Robert N.; Lambrechts, Diether; Neven, Patrick; Wildiers, Hans; van Limbergen, Erik; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Couch, Fergus J.; Olson, Janet E.; Hallberg, Emily; Vachon, Celine; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A.; van der Luijt, Rob B.; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Yoo, Keun-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Guenel, Pascal; Truong, Therese; Mulot, Claire; Sanchez, Marie; Burwinkel, Barbara; Marme, Frederik; Surowy, Harald; Sohn, Christof; Wu, Anna H.; Tseng, Chiu-chen; Van den Berg, David; Stram, Daniel O.; Gonzalez-Neira, Anna; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Lindblom, Annika; Margolin, Sara; Teo, Soo Hwang; Yip, Cheng Har; Taib, Nur Aishah Mohd; Tan, Gie-Hooi; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W. M.; Collee, J. Margriet; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Hopper, John L.; Southey, Melissa C.; Tsimiklis, Helen; Apicella, Carmel; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Kristensen, Vessela N.; Nord, Silje; Alnaes, Grethe I. Grenaker; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Canzian, Federico; Trichopoulos, Dimitrios; Peeters, Petra; Lund, Eiliv; Sund, Malin; Khaw, Kay-Tee; Gunter, Marc J.; Palli, Domenico; Mortensen, Lotte Maxild; Dossus, Laure; Huerta, Jose-Maria; Meindl, Alfons; Schmutzler, Rita K.; Sutter, Christian; Yang, Rongxi; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Chan, Ching Wan; Fasching, Peter A.; Hein, Alexander; Beckmann, Matthias W.; Haeberle, Lothar; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Swerdlow, Anthony J.; Brinton, Louise; Garcia-Closas, Montserrat; Zheng, Wei; Halverson, Sandra L.; Shrubsole, Martha; Long, Jirong; Goldberg, Mark S.; Labreche, France; Dumont, Martine; Winqvist, Robert; Pylkas, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Bruening, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Bogdanova, Natalia V.; Doerk, Thilo; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; Van Asperen, Christi J.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Huzarski, Tomasz; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Kabisch, Maria; Torres, Diana; Neuhausen, Susan L.; Anton-Culver, Hoda; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S.; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Pita, Guillermo; Rosario Alonso, M.; Alvarez, Nuria; Herrero, Daniel; Simard, Jacques; Pharoah, Paul P. D. P.; Kraft, Peter; Dunning, Alison M.; Chenevix-Trench, Georgia; Hall, Per; Easton, Douglas F.

    Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining similar to 14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising

  6. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    DEFF Research Database (Denmark)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara

    2015-01-01

    Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748...

  7. Meta-analysis of genome-wide association studies for personality

    NARCIS (Netherlands)

    M.H.M. de Moor; P.T. Costa Jr; A. Terracciano; R.F. Krueger; E.J.C. de Geus (Eco); T. Toshiko; B.W.J.H. Penninx (Brenda); T. Esko; P.A.F. Madden (Pamela); J. Derringer; N. Amin (Najaf); G.A.H.M. Willemsen (Gonneke); J.J. Hottenga (Jouke Jan); M.A. Distel (Marijn); M. Uda (Manuela); S. Sanna (Serena); P. Spinhoven; C.A. Hartman; P.F. Sullivan (Patrick); A. Realo; J. Allik; A.C. Heath; M.L. Pergadia; P. Lin; R. Grucza; T. Nutile; M. Ciullo; D. Rujescu (Dan); I. Giegling (Ina); B. Konte; E. Widen (Elisabeth); D.L. Cousminer (Diana); J.G. Eriksson; A. Palotie; L. Peltonen; M. Luciano (Michelle); A. Tenesa (Albert); G. Davies; L.M. Lopez; N.K. Hansell (Narelle); S.E. Medland (Sarah Elizabeth); L. Ferrucci; D. Schlessinger; G.W. Montgomery; M.J. Wright (Margaret); Y.S. Aulchenko (Yurii); A.C.J.W. Janssens (Cécile); B.A. Oostra (Ben); A. Metspalu (Andres); I.J. Deary; K. Räikkönen (Katri); L.J. Bierut (Laura); N.G. Martin; C.M. van Duijn (Cornelia); D.I. Boomsma (Dorret); G.R. Abecasis (Gonçalo); A. Agrawal (Arpana)

    2012-01-01

    textabstractPersonality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide

  8. Periodontal disease and risk of chronic obstructive pulmonary disease: a meta-analysis of observational studies.

    Directory of Open Access Journals (Sweden)

    Xian-Tao Zeng

    Full Text Available BACKGROUND: Many epidemiological studies have found a positive association between periodontal disease (PD and risk of chronic obstructive pulmonary disease (COPD, but this association is varied and even contradictory among studies. We performed a meta-analysis to ascertain the relationship between PD and COPD. METHODS: PubMed and Embase database were searched up to January 10, 2012, for relevant observational studies on the association between PD and risk of COPD. Data from the studies selected were extracted and analyzed independently by two authors. The meta-analysis was performed using the Comprehensive Meta-Analysis software. RESULTS: Fourteen observational studies (one nested case-control, eight case-control, and five cross-sectional involving 3,988 COPD patients were yielded. Based on random-effects meta-analysis, a significant association between PD and COPD was identified (odds ratio = 2.08, 95% confidence interval = 1.48-2.91; P<0.001, with sensitivity analysis showing that the result was robust. Subgroups analyses according to study design, ethnicity, assessment of PD/COPD, and adjusted/unadjusted odds ratios also revealed a significant association. Publication bias was detected. CONCLUSIONS: Based on current evidence, PD is a significant and independent risk factor of COPD. However, whether a causal relationships exists remains unclear. Morever, we suggest performing randomized controlled trails to explore whether periodontal interventions are beneficial in regulating COPD pathogenesis and progression.

  9. Lycopene Consumption and Risk of Colorectal Cancer: A Meta-Analysis of Observational Studies.

    Science.gov (United States)

    Wang, Xin; Yang, Hui-Hui; Liu, Yan; Zhou, Quan; Chen, Zi-Hua

    2016-10-01

    A number of epidemiological studies have explored the association between lycopene or lycopene-rich food intake and the risk of colorectal cancer, but the results of these studies have not been consistent. We conducted a systematic review and meta-analysis of studies published in the PubMed and EMBASE databases to quantitatively assess the association between lycopene consumption and the risk of colorectal cancer. A total of 15 studies were included in the meta-analysis, and the summary relative risk (RR) for highest versus lowest category indicated no significant association between lycopene consumption and the risk of colorectal cancer [RR = 0.94, 95% confidence interval (CI): 0.80-1.10]. However, a significant inverse association was observed between lycopene consumption and the site of cancer in the colon (RR = 0.88, 95% CI: 0.81-0.96). We also found that the incidence of colon cancer and lycopene intake did not exhibit dose-response relationships. The Grades of Recommendations Assessment, Development and Evaluation (GRADE) quality in our study was very low. In conclusion, this meta-analysis indicates that lycopene consumption is not associated with the risk of colorectal cancer. Further research will be needed in this area to provide conclusive evidence.

  10. Schizophrenia symptomatic associations with diffusion tensor imaging measured fractional anisotropy of brain: a meta-analysis.

    Science.gov (United States)

    Yang, Xu; Cao, Ding; Liang, Xiumei; Zhao, Jiannong

    2017-07-01

    Several studies have examined the relationships between diffusion tensor imaging (DTI)-measured fractional anisotropy (FA) and the symptoms of schizophrenia, but results vary across the studies. The aim of this study was to carry out a meta-analysis of correlation coefficients reported by relevant studies to evaluate the correlative relationships between FA of various parts of the brain and schizophrenia symptomatic assessments. Literature was searched in several electronic databases, and study selection was based on précised eligibility criteria. Correlation coefficients between FA of a part of the brain and schizophrenia symptom were first converted into Fisher's z-scores for meta-analyses, and then overall effect sizes were back transformed to correlation coefficients. Thirty-three studies (1121 schizophrenia patients; age 32.66 years [95% confidence interval (CI) 30.19, 35.13]; 65.95 % [57.63, 74.28] males) were included in this meta-analysis. Age was inversely associated with brain FA (z-scores [95% CI] -0.23 [-0.14, -0.32]; p ˂ 0.00001). Brain FA of various areas was inversely associated with negative symptoms of schizophrenia (z-score -0.30 [-0.23, -0.36]; p ˂ 0.00001) but was positively associated with positive symptoms of schizophrenia (z-score 0.16 [0.04, 0.27]; p = 0.007) and general psychopathology of schizophrenia (z-score 0.26 [0.15, 0.37]; p = 0.00001). Although, DTI-measured brain FA is found to be inversely associated with negative symptoms and positively associated with positive symptoms and general psychopathology of schizophrenia, the effect sizes of these correlations are low and may not be clinically significant. Moreover, brain FA was also negatively associated with age of patients.

  11. Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Sarah L. Kerns

    2016-08-01

    Full Text Available Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity and single nucleotide polymorphism (SNP associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08–4.69, p-value 4.16 × 10−8 and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90–3.86, p-value = 3.21 × 10−8. These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.

  12. The experience of electroconvulsive therapy and its impact on associated stigma: A meta-analysis.

    Science.gov (United States)

    Aoki, Yuta; Yamaguchi, Sosei; Ando, Shuntaro; Sasaki, Natsuki; Bernick, Peter J; Akiyama, Tsuyoshi

    2016-12-01

    Despite its efficacy and safety, electroconvulsive therapy (ECT) is underutilized, in part due to stigma associated with the treatment. The aim of this study was to test the hypothesis that experiencing ECT has an impact on associated stigma, as measured by patient and family knowledge of and attitudes toward ECT. A comprehensive literature search was conducted using MEDLINE, EMBASE and PsycINFO. Studies with cross-sectional and/or longitudinal designs were identified. Studies were further categorized into subcategories based on participant type (patients or patient family members) and outcome domain (knowledge or attitudes). Effect size (Cohen's d) was calculated for each study and then integrated into each subcategory (participant type by outcome domain) using a random effect model. Eight studies were identified as being eligible for analysis. Two studies were cross-sectional, five were longitudinal and one incorporated both designs. Analysis of the longitudinal studies indicated that experiencing ECT both increased knowledge of and improved attitudes toward ECT in patients; in family members of patients, analysis showed significant positive change in knowledge of ECT, but no significant change in attitudes toward ECT. Experience with ECT may have a positive impact on knowledge of and attitudes toward ECT. However, the quality of evidence of included studies was low; further research is required in order to clarify the relationship and to identify information of use to individuals considering ECT as a treatment option. © The Author(s) 2016.

  13. Depression and oxidative stress: results from a meta-analysis of observational studies.

    Science.gov (United States)

    Palta, Priya; Samuel, Laura J; Miller, Edgar R; Szanton, Sarah L

    2014-01-01

    To perform a systematic review and meta-analysis that quantitatively tests and summarizes the hypothesis that depression results in elevated oxidative stress and lower antioxidant levels. We performed a meta-analysis of studies that reported an association between depression and oxidative stress and/or antioxidant status markers. PubMed and EMBASE databases were searched for articles published from January 1980 through December 2012. A random-effects model, weighted by inverse variance, was performed to pool standard deviation (Cohen's d) effect size estimates across studies for oxidative stress and antioxidant status measures, separately. Twenty-three studies with 4980 participants were included in the meta-analysis. Depression was most commonly measured using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. A Cohen's d effect size of 0.55 (95% confidence interval = 0.47-0.63) was found for the association between depression and oxidative stress, indicating a roughly 0.55 of 1-standard-deviation increase in oxidative stress among individuals with depression compared with those without depression. The results of the studies displayed significant heterogeneity (I(2) = 80.0%, p < .001). A statistically significant effect was also observed for the association between depression and antioxidant status markers (Cohen's d = -0.24, 95% confidence interval = -0.33 to -0.15). This meta-analysis observed an association between depression and oxidative stress and antioxidant status across many different studies. Differences in measures of depression and markers of oxidative stress and antioxidant status markers could account for the observed heterogeneity. These findings suggest that well-established associations between depression and poor heath outcomes may be mediated by high oxidative stress.

  14. Association between polymorphism in STAT4 gene and risk of rheumatoid arthritis: a meta-analysis.

    Science.gov (United States)

    Tong, Guanghui; Zhang, Xiaochen; Tong, Weiwei; Liu, Yong

    2013-05-01

    Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease, affecting 1% of the population worldwide. Single nucleotide polymorphisms (SNPs) of signal transducer and activator of transcription 4 (STAT4) gene are suspected to have some relationship with the risk of RA. This meta-analysis aimed to evaluate the relationship between the polymorphism rs7574865 in STAT4 gene with RA and also examine whether the associations that have been reported in these studies differ between ethnic groups. We retrieved the relevant articles from PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) databases. The odds ratios (ORs) and their 95% confidence intervals (95% CIs) associated with the minor T allele of STAT4 rs7574865 SNP were extracted from the published studies and included in the analysis. Meta-analyses were performed on the total data set and separately for the major ethnic groups and RF and anti-CCP status. All analyses were performed using the Stata software. Twenty-three articles were included in the present analysis. Meta-analysis showed an association between the STAT4 polymorphism and RA in all subjects (OR=1.299, 95%CI=1.230-1.371, Prs7574865 T allele was significantly associated with RA in both Caucasians and Asians, in both positive and negative RF patients versus controls, also significantly in the presence of anti-CCP, both positive and negative. As for genotypes of rs7574865 polymorphism, all the results were significant, no matter in total subjects or stratified analyses by ethnic groups or by RF and anti-CCP status. Genetic polymorphism rs7574865 in STAT4 gene might be associated with RA susceptibility in total subjects, major ethnic groups and different status of anti-CCP or RF. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  15. Elastic-net regularization approaches for genome-wide association studies of rheumatoid arthritis.

    Science.gov (United States)

    Cho, Seoae; Kim, Haseong; Oh, Sohee; Kim, Kyunga; Park, Taesung

    2009-12-15

    The current trend in genome-wide association studies is to identify regions where the true disease-causing genes may lie by evaluating thousands of single-nucleotide polymorphisms (SNPs) across the whole genome. However, many challenges exist in detecting disease-causing genes among the thousands of SNPs. Examples include multicollinearity and multiple testing issues, especially when a large number of correlated SNPs are simultaneously tested. Multicollinearity can often occur when predictor variables in a multiple regression model are highly correlated, and can cause imprecise estimation of association. In this study, we propose a simple stepwise procedure that identifies disease-causing SNPs simultaneously by employing elastic-net regularization, a variable selection method that allows one to address multicollinearity. At Step 1, the single-marker association analysis was conducted to screen SNPs. At Step 2, the multiple-marker association was scanned based on the elastic-net regularization. The proposed approach was applied to the rheumatoid arthritis (RA) case-control data set of Genetic Analysis Workshop 16. While the selected SNPs at the screening step are located mostly on chromosome 6, the elastic-net approach identified putative RA-related SNPs on other chromosomes in an increased proportion. For some of those putative RA-related SNPs, we identified the interactions with sex, a well known factor affecting RA susceptibility.

  16. Associations between Dietary Patterns and Impaired Fasting Glucose in Chinese Men: A Cross-Sectional Study.

    Science.gov (United States)

    Zhang, Meilin; Zhu, Yufeng; Li, Ping; Chang, Hong; Wang, Xuan; Liu, Weiqiao; Zhang, Yuwen; Huang, Guowei

    2015-09-21

    Few studies have examined the association between Asian dietary pattern and prediabetes, in particular, the Chinese diet. We conducted a cross-sectional study to identify dietary patterns associated with impaired fasting glucose (IFG) which considered a state of prediabetes in Chinese men. The study included 1495 Chinese men aged 20 to 75 years. Information about diet was obtained using an 81-item food frequency questionnaire (FFQ), and 21 predefined food groups were considered in a factor analysis. Three dietary patterns were generated by factor analysis: (1) a vegetables-fruits pattern; (2) an animal offal-dessert pattern; and (3) a white rice-red meat pattern. The multivariate-adjusted odds ratio (OR) of IFG for the highest tertile of the animal offal-dessert pattern in comparison with the lowest tertile was 3.15 (95% confidence intervals (CI): 1.87-5.30). The vegetables-fruits dietary pattern was negatively associated with the risk of IFG, but a significant association was observed only in the third tertile. There was no significant association between IFG and the white rice-red meat pattern. Our findings indicated that the vegetables-fruits dietary pattern was inversely associated with IFG, whereas the animal offal-dessert pattern was associated with an increased risk of IFG in Chinese men. Further prospective studies are needed to elucidate the diet-prediabetes relationships.

  17. Association of PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with rheumatoid arthritis: A meta-analysis update.

    Science.gov (United States)

    Elshazli, Rami; Settin, Ahmad

    2015-08-01

    Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The genes encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) and signal transducer and activator of transcription 4 (STAT4) have been reported to be associated with RA in several ethnic populations. This work aims to assess the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility through an updated meta-analysis of available case-control studies. A literature search of all relevant studies published from January 2007 up to December 2014 was conducted using Pubmed and Science Direct databases. The observed studies that were related to an association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility were identified. Meta-analysis of the pooled and stratified data was done and assessed using varied genetic models. Thirty-seven case-control studies with a total of 47 comparisons (29 for PTPN22 rs2476601 polymorphism and 18 for STAT4 rs7574865 polymorphism) met our inclusion criteria. The meta-analysis showed an association between PTPN22 T allele, CT+TT and TT genotypes with RA susceptibility. Furthermore, The meta-analysis showed an association between STAT4 T allele, GT+TT and TT genotypes with RA susceptibility. Stratification of RA patients according to ethnic groups showed that PTPN22 T allele, CT+TT genotypes, STAT4 T allele and STAT4 GT+TT were significantly associated with RA in European, Asian, African subjects, while PTPN22 TT genotype was significantly associated with RA in European but not in Asian and African subjects and STAT4 TT genotype was significantly associated with RA in European and Asian but not in African subject. A subgroup analysis according to the presence or absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies revealed that the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility

  18. Accident rate analysis for well drilling at Kuban' morneftegazprom association

    Energy Technology Data Exchange (ETDEWEB)

    Sukhanov, V B; Kezchikov, A V

    1981-01-01

    Analysis of emergency procedures at the association during 1976--1977 is provided. Conclusions were made and plans established for basic directions of engineering-production operations and for association and enterprise division sections with regard to lowering accident rate and time period necessary to eliminate accidents.

  19. Factors Associated With Healthcare-Acquired Catheter-Associated Urinary Tract Infections: Analysis Using Multiple Data Sources and Data Mining Techniques.

    Science.gov (United States)

    Park, Jung In; Bliss, Donna Z; Chi, Chih-Lin; Delaney, Connie W; Westra, Bonnie L

    The purpose of this study was to identify factors associated with healthcare-acquired catheter-associated urinary tract infections (HA-CAUTIs) using multiple data sources and data mining techniques. Three data sets were integrated for analysis: electronic health record data from a university hospital in the Midwestern United States was combined with staffing and environmental data from the hospital's National Database of Nursing Quality Indicators and a list of patients with HA-CAUTIs. Three data mining techniques were used for identification of factors associated with HA-CAUTI: decision trees, logistic regression, and support vector machines. Fewer total nursing hours per patient-day, lower percentage of direct care RNs with specialty nursing certification, higher percentage of direct care RNs with associate's degree in nursing, and higher percentage of direct care RNs with BSN, MSN, or doctoral degree are associated with HA-CAUTI occurrence. The results also support the association of the following factors with HA-CAUTI identified by previous studies: female gender; older age (>50 years); longer length of stay; severe underlying disease; glucose lab results (>200 mg/dL); longer use of the catheter; and RN staffing. Additional findings from this study demonstrated that the presence of more nurses with specialty nursing certifications can reduce HA-CAUTI occurrence. While there may be valid reasons for leaving in a urinary catheter, findings show that having a catheter in for more than 48 hours contributes to HA-CAUTI occurrence. Finally, the findings suggest that more nursing hours per patient-day are related to better patient outcomes.

  20. [Clinical-demographic factors associated with fear-avoidance in subjects with non-specific chronic low back pain in Primary Care: secondary analysis of intervention study].

    Science.gov (United States)

    Díaz-Cerrillo, Juan Luis; Rondón-Ramos, Antonio; Clavero-Cano, Susana; Pérez-González, Rita; Martinez-Calderon, Javier; Luque-Suarez, Alejandro

    2018-01-30

    To describe some sociodemographics and clinical characteristics of subjects with Non-specific Chronic Low Back Pain (NCLBP) in Primary Care, as well as to investigate their association with Fear-Avoidance (FA). Cross-sectional. Secondary analysis of an intervention study. Basic Health Areas in Costa del Sol Health District (Málaga, Spain). An analysis was performed on 147 subjects with NCLBP from a previous intervention study database in Primary Care Physiotherapy (PCP). Characteristics: age 18-65; understanding of the Spanish language; absence of cognitive disorders, fibromyalgia or dorsolumbar surgery, and to be able to perform physical exercise. The main variable was FA level (FABQ and the FABQ-PA and FABQ-W) sub-scales. Clinical variables included: pain (NRPS-11), disability (RMQ), evolution, previous treatments and diagnostic imaging. The sociodemographic variables included: gender, age, educational level, and employment status. Just over half (51.7%) of the subjects had high FA on the FABQ-PA sub-scale. Sick leave (SL) [β=24.45 (P=.009 * ); β=13.03 (P=.016 * ); β=14.04 (P=.011 * ) for FABQ, FABQ-PA and FABQ-W, respectively]; primary studies level [β=15.09 (P=.01 * ); β=9.73 (P=.01 * ) for FABQ and FABQ-PA], and disability [β=1.45 (P<.001); β=0.61 (P<.001); β=0.68 (P<.001) for FABQ, FABQ-PA and FABQ-W, respectively] were associated with FA when they were modeled by multivariate regression. Some sociodemographic and clinical features of the NCLBP population are presented. Imaging tests (81.63%) and previous passive treatments (55.78%) could reflect problems of adherence to recommendations of CPGs. Sick leave, primary studies level, and disability were associated with FA. The findings should be interpreted in the light of possible limitations. Some suggestions for clinical practice are provided. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  1. Retrospective analysis of main and interaction effects in genetic association studies of human complex traits

    DEFF Research Database (Denmark)

    Tan, Qihua; Christiansen, Lene; Brasch-Andersen, Charlotte

    2007-01-01

    with that of the case-only model. RESULTS: Results from our simulation study indicate that our retrospective model exhibits high power in capturing even relatively small effect with reasonable sample sizes. Application of our method to data from an association study on the catalase -262C/T promoter polymorphism...

  2. Meta-analysis of the association between short-term exposure to ambient ozone and respiratory hospital admissions

    International Nuclear Information System (INIS)

    Ji Meng; Bell, Michelle L; Cohan, Daniel S

    2011-01-01

    Ozone is associated with health impacts including respiratory outcomes; however, results differ across studies. Meta-analysis is an increasingly important approach to synthesizing evidence across studies. We conducted meta-analysis of short-term ozone exposure and respiratory hospitalizations to evaluate variation across studies and explore some of the challenges in meta-analysis. We identified 136 estimates from 96 studies and investigated how estimates differed by age, ozone metric, season, lag, region, disease category, and hospitalization type. Overall results indicate associations between ozone and various kinds of respiratory hospitalizations; however, study characteristics affected risk estimates. Estimates were similar, but higher, for the elderly compared to all ages and for previous day exposure compared to same day exposure. Comparison across studies was hindered by variation in definitions of disease categories, as some (e.g., asthma) were identified through ≥ 3 different sets of ICD codes. Although not all analyses exhibited evidence of publication bias, adjustment for publication bias generally lowered overall estimates. Emergency hospitalizations for total respiratory disease increased by 4.47% (95% interval: 2.48, 6.50%) per 10 ppb 24 h ozone among the elderly without adjustment for publication bias and 2.97% (1.05, 4.94%) with adjustment. Comparison of multi-city study results and meta-analysis based on single-city studies further suggested publication bias.

  3. Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis.

    Science.gov (United States)

    Zhu, Ming; Zhang, Jie; Nie, Shaofa; Yan, Weirong

    2012-09-01

    There have been many studies concerning the associations of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T polymorphisms with pregnancy induced hypertension (PIH) among Chinese populations. However, the results were inconsistent, prompting the necessity of meta-analysis. Studies published in English and Chinese were mainly searched in EMbase, PubMed and CBM up to January 2012. Twenty-three studies with 3,551 subjects for ACE I/D and seven studies with 1,296 subjects for AGT M235T were included. Significant associations were found between ACE I/D and PIH under dominant, recessive and allelic models. A separate analysis confined to preeclampsia suggested that ACE I/D was associated with preeclampsia under recessive model and allelic model, but not dominant model. Stratified analyses were conducted as meta-regression analysis indicated that the sample size of case group was a significant source of heterogeneity, which suggested no significant association between ACE I/D and PIH in the subgroup of more than 100 cases. Associations were found between AGT M235T and PIH under dominant genetic model (OR = 1.59; 95 %CI: 1.04-2.42), recessive genetic model (OR = 1.60; 95 %CI: 1.07-2.40), and allelic model (OR = 1.40; 95 %CI: 1.17-1.68). No publication bias was found in either meta-analysis. The present meta-analysis suggested significant associations between ACE I/D, AGT M235T and PIH in Chinese populations. However, no significant association was found between ACE I/D and PIH in the subgroup of more than 100 cases. Studies with larger sample sizes are necessary to investigate the associations between gene polymorphisms and PIH in Chinese populations.

  4. Comparative proteomics analysis of oral cancer cell lines: identification of cancer associated proteins

    Science.gov (United States)

    2014-01-01

    Background A limiting factor in performing proteomics analysis on cancerous cells is the difficulty in obtaining sufficient amounts of starting material. Cell lines can be used as a simplified model system for studying changes that accompany tumorigenesis. This study used two-dimensional gel electrophoresis (2DE) to compare the whole cell proteome of oral cancer cell lines vs normal cells in an attempt to identify cancer associated proteins. Results Three primary cell cultures of normal cells with a limited lifespan without hTERT immortalization have been successfully established. 2DE was used to compare the whole cell proteome of these cells with that of three oral cancer cell lines. Twenty four protein spots were found to have changed in abundance. MALDI TOF/TOF was then used to determine the identity of these proteins. Identified proteins were classified into seven functional categories – structural proteins, enzymes, regulatory proteins, chaperones and others. IPA core analysis predicted that 18 proteins were related to cancer with involvements in hyperplasia, metastasis, invasion, growth and tumorigenesis. The mRNA expressions of two proteins – 14-3-3 protein sigma and Stress-induced-phosphoprotein 1 – were found to correlate with the corresponding proteins’ abundance. Conclusions The outcome of this analysis demonstrated that a comparative study of whole cell proteome of cancer versus normal cell lines can be used to identify cancer associated proteins. PMID:24422745

  5. [Meta-analysis of association between organophosphorus pesticides and aplastic anemia].

    Science.gov (United States)

    Zhang, Ji; Yang, Tubao

    2015-09-01

    To evaluate the association between organophosphorus pesticides and aplastic anemia, and provide scientific evidence for the primary prevention of aplastic anemia. The published papers of case control studies on the association between organophosphorus pesticides and aplastic anemia from January 1990 to August 2014 were collected from Chinese BioMedical Literature Base (CBM), Chinese National Knowledge Infrastructure (CNKI), PubMed and EMBASE. The papers which met the inclusion criteria were evaluated. The pooled odds ratios (OR) and 95% confidence interval (CI) of organophosphorus pesticides were calculated with software Review Manager 5.0. Subgroup analysis were conducted for different population and different usage of organophosphorus pesticides. A total of 9 papers were selected, involving 5 833 subjects (1 404 cases and 4 429 controls). The results showed that organophosphorus pesticides could increase the risk of aplastic anemia (OR=1.97, 95% CI: 1.60-2.44) . Subgroup analysis showed that Asian (OR=2.01, 95% CI: 1.52-2.66) had higher risk of aplastic anemia than American or European (OR=1.93, 95% CI: 1.39-2.67) . Using pure organophosphorus pesticides (OR=2.15, 95% CI: 1.60-2.88) was more prone to cause aplastic anemia than using the mixture of organophosphorus pesticides (OR=1.82, 95% CI: 1.34-2.47). The analysis indicated that organophosphorus pesticides might be a risk factor for aplastic anemia. Reducing organophosphorus pesticides exposure in daily life and industrial or agricultural production could prevent the incidence of aplastic anemia.

  6. Dietary Fat Intake and Risk of Gastric Cancer: A Meta-Analysis of Observational Studies

    Science.gov (United States)

    Liu, Xiao; Meng, Qingyang; Xi, Qiulei; Zhuang, Qiulin; Han, Yusong; Gao, Ying; Ding, Qiurong; Wu, Guohao

    2015-01-01

    Background and Objectives Consumption of dietary fat has been reported to be associated with gastric cancer risk, but the results of epidemiologic studies remain inconsistent. We conducted a meta-analysis to summarize the evidence regarding the association between dietary fat intake and gastric cancer risk. Methods A comprehensive search of PubMed and EMBASE was performed to identify observational studies providing quantitative estimates between dietary fat and gastric cancer risk. Random effects model was used to calculate the summary relative risk(SRR) in the highest versus lowest analysis. Categorical dose-response analysis was conducted to quantify the association between dietary fat intake and gastric cancer risk. Heterogeneity among studies was evaluated using I2 and tau2(between study variance)statistics. Subgroup analysis and publication bias analysis were also performed. Results Twenty-two articles were included in the meta-analysis. The SRR for gastric cancer was 1.18 for individuals with highest intake versus lowest intake of total fat (95% confidence interval [CI]: 0.999–1.39; n = 28; Pgastric cancer risk were observed. Conclusions Our results suggest that intake of total fat is potentially positively associated with gastric cancer risk, and specific subtypes of fats account for different effects. However, these findings should be confirmed by further well-designed cohort studieswith detailed dietary assessments and strict control of confounders. PMID:26402223

  7. A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence.

    Science.gov (United States)

    Spain, S L; Pedroso, I; Kadeva, N; Miller, M B; Iacono, W G; McGue, M; Stergiakouli, E; Davey Smith, G; Putallaz, M; Lubinski, D; Meaburn, E L; Plomin, R; Simpson, M A

    2016-08-01

    Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case-control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence.

  8. Are glutathione S-transferase polymorphisms (GSTM1, GSTT1) associated with primary open angle glaucoma? A meta-analysis.

    Science.gov (United States)

    Lu, Yan; Shi, Yuhua; Yin, Jie; Huang, Zhenping

    2013-09-15

    Glutathione S-transferase (GST) variants have been considered as risk factors for the pathogenesis of primary open angle glaucoma (POAG). However, the results have been inconsistent. In this study, we performed a meta-analysis to assess the association between GSTM1 and GSTT1 null genotypes and the risk for POAG. Published literature from PubMed and EMBASE databases was retrieved. All studies evaluating the association between GSTM1/GSTT1 variants and POAG were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model. 14 studies (1711 POAG cases and 1537 controls) were included in the meta-analysis of GSTM1 genotypes and 10 studies (1306 POAG cases and 1114 controls) were included in the meta-analysis of GSTT1 genotypes. The overall result showed that the association between GSTM1 and GSTT1 null genotypes and risk for POAG was not statistically significant (GSTM1: OR=1.19, 95% CI=0.82-1.73, p=0.361; GSTT1: OR=1.26, 95% CI=0.77-2.06, p=0.365). The results by ethnicity showed that the association between the GSTM1 null genotype and risk for POAG is statistically significant in East Asians (OR=1.41, 95% CI=1.04-1.90, p=0.026), but not in Caucasians (OR=1.13, 95% CI=0.69-1.84, p=0.638) and Latin-American (OR=1.09, 95% CI=0.62-1.92, p=0.767). In addition, there was no significant association of GSTT1 null genotype with risk for POAG in either ethnic population. The present meta-analysis suggested that there might be a significant association of GSTM1 null genotype with POAG risk in East Asians. © 2013 Elsevier B.V. All rights reserved.

  9. College students' drinking motives and social-contextual factors: Comparing associations across levels of analysis.

    Science.gov (United States)

    O'Hara, Ross E; Armeli, Stephen; Tennen, Howard

    2015-06-01

    Prior investigations have established between-person associations between drinking motives and both levels of alcohol use and social-contextual factors surrounding that use, but these relations have yet to be examined at the within-person level of analysis. Moreover, exploring previously posited subtypes of coping motives (i.e., coping with depression, anxiety, and anger) may shed light on the within-person processes underlying drinking to cope. In this daily diary study of college student drinking (N = 722; 54% female), students reported each day how many drinks they consumed the previous evening in both social and nonsocial settings along with their motives for each drinking episode. Additionally, they reported whether they attended a party the evening before, the number of people they were with, the gender makeup of that group, and their perceptions of their companions' drinking prevalence and quantity. External reasons for drinking-social and conformity motives-showed patterns largely consistent across levels of analysis and in agreement with motivational models. However, internal reasons for drinking-enhancement and coping motives-demonstrated divergent associations that suggest different processes across levels of analysis. Finally, coping subtypes showed differing associations with drinking levels and social-contextual factors dependent on the predisposing emotion and the level of analysis. These results suggest that internal drinking motives have unique state and trait components, which could have important implications for the application of motivational models to prevention and treatment efforts. We recommend including drinking motives (including coping subtypes) as within-person measures in future microlongitudinal studies. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  10. College Students’ Drinking Motives and Social-Contextual Factors: Comparing Associations across Levels of Analysis

    Science.gov (United States)

    O'Hara, Ross E.; Armeli, Stephen; Tennen, Howard

    2014-01-01

    Prior investigations have established between-person associations between drinking motives and both levels of alcohol use and social-contextual factors surrounding that use, but these relations have yet to be examined at the within-person level of analysis. Moreover, exploring previously posited subtypes of coping motives (i.e., coping with depression, anxiety, and anger) may shed light on the within-person processes underlying drinking to cope. In this daily diary study of college student drinking (N = 722; 54% female), students reported each day how many drinks they consumed the previous evening in both social and nonsocial settings along with their motives for each drinking episode. Additionally, they reported whether they attended a party the evening before, the number of people they were with, the gender makeup of that group, and their perceptions of their companions’ drinking prevalence and quantity. External reasons for drinking—social and conformity motives—showed patterns largely consistent across levels of analysis and in agreement with motivational models. However, internal reasons for drinking—enhancement and coping motives—demonstrated divergent associations that suggest different processes across levels of analysis. Finally, coping subtypes showed differing associations with drinking levels and social-contextual factors dependent on the predisposing emotion and the level of analysis. These results suggest that internal drinking motives have unique state and trait components, which could have important implications for the application of motivational models to prevention and treatment efforts. We recommend including drinking motives (including coping subtypes) as within-person measures in future micro-longitudinal studies. PMID:25546143

  11. Immunochip analysis identifies association of the RAD50/IL13 region with human longevity.

    Science.gov (United States)

    Flachsbart, Friederike; Ellinghaus, David; Gentschew, Liljana; Heinsen, Femke-Anouska; Caliebe, Amke; Christiansen, Lene; Nygaard, Marianne; Christensen, Kaare; Blanché, Hélène; Deleuze, Jean-François; Derbois, Céline; Galan, Pilar; Büning, Carsten; Brand, Stephan; Peters, Anette; Strauch, Konstantin; Müller-Nurasyid, Martina; Hoffmann, Per; Nöthen, Markus M; Lieb, Wolfgang; Franke, Andre; Schreiber, Stefan; Nebel, Almut

    2016-06-01

    Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls. First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (PI mmunochip  = 7.01 × 10(-9) ) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PI mmunochip  association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta-analysis of the combined French and Danish data after adjusting for multiple testing. In a meta-analysis of all three samples, rs2706372 reached a P-value of PI mmunochip+Repl  = 5.42 × 10(-7) (OR = 1.20; 95% CI = 1.12-1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  12. Association of endothelial nitric oxide synthase gene polymorphisms with coronary artery disease: an updated meta-analysis and systematic review.

    Directory of Open Access Journals (Sweden)

    Himanshu Rai

    Full Text Available Several association studies of endothelial nitric oxide synthase (NOS3 gene polymorphisms with respect to coronary artery disease (CAD have been published in the past two decades. However, their association with the disease, especially among different ethnic subgroups, still remains controversial. This prompted us to conduct a systematic review and an updated structured meta-analysis, which is the largest so far (89 articles, 132 separate studies, and a sample size of 69,235, examining association of three polymorphic forms of the NOS3 gene (i.e. Glu298Asp, T786-C and 27 bp VNTR b/a with CAD. In a subgroup analysis, we tested their association separately among published studies originating predominantly from European, Middle Eastern, Asian, Asian-Indian and African ancestries. The pooled analysis confirmed the association of all the three selected SNP with CAD in three different genetic models transcending all ancestries worldwide. The Glu298Asp polymorphism showed strongest association (OR range = 1.28-1.52, and P<0.00001 for all comparisons, followed by T786-C (OR range = 1.34-1.42, and P<0.00001 for all comparisons and 4b/a, (OR range = 1.19-1.41, and P ≤ 0.002 for all comparisons in our pooled analysis. Subgroup analysis revealed that Glu298Asp (OR range = 1.54-1.87, and P<0.004 for all comparisons and 4b/a (OR range = 1.71-3.02, and P<0.00001 for all comparisons have highest degree of association amongst the Middle Easterners. On the other hand, T786-C and its minor allele seem to carry a highest risk for CAD among subjects of Asian ancestry (OR range = 1.61-1.90, and P ≤ 0.01 for all comparisons.

  13. Meta-analysis of the association between NLRP1 polymorphisms and the susceptibility to vitiligo and associated autoimmune diseases

    OpenAIRE

    Li, Juan; Yan, Min; Zhang, Yuan; Feng, Chao; Wang, Huicong; Wang, Cuiyu; Sun, Li

    2017-01-01

    Genetic variants are linked to vitiligo and associated autoimmune diseases. We performed a meta-analysis to evaluate the effects of the rs12150220, rs2670660, and rs6502867 polymorphisms within the human NLR Family Pyrin Domain Containing 1 (NLRP1) gene. We initially identified 1,306 candidate articles through literature searches of Pubmed, WOS, Embase, CNKI, WANFANGI, Ovid, Scopus, and Cochrane in July 2017. After strict screening, we included 19 eligible case-control studies, and analyzed t...

  14. Line-item analysis of the Aberrant Behavior Checklist: results from two studies of aripiprazole in the treatment of irritability associated with autistic disorder.

    Science.gov (United States)

    Aman, Michael G; Kasper, William; Manos, George; Mathew, Suja; Marcus, Ronald; Owen, Randall; Mankoski, Raymond

    2010-10-01

    The aim of this study was to evaluate the efficacy of aripiprazole in the treatment of discrete symptoms of irritability associated with autistic disorder, as well as other symptoms captured on the Aberrant Behavior Checklist (ABC). This was a post hoc analysis of data from two 8-week, randomized, double-blind, multicenter trials to evaluate the efficacy of aripiprazole dosed flexibly (2-15 mg/day, n=47) or fixed (5, 10, or 15 mg/day, n = 166) versus placebo (flexibly dosed, n = 51; fixed dose, n = 52). The effects of treatment on the 58 ABC items were evaluated. Statistically significantly greater improvement was seen with aripiprazole versus placebo (p autistic disorder, particularly with respect to symptoms associated with tantrum behavior.

  15. Association between dietary nitrate and nitrite intake and site-specific cancer risk: evidence from observational studies

    Science.gov (United States)

    Jia, Hui-Xun; Liang, Fei; Yuan, Jing; Zhu, Ji

    2016-01-01

    Epidemiological studies have reported inconsistent findings on the association between dietary nitrate and nitrite intake and cancer risk. We performed a meta-analysis of epidemiological studies to summarize available evidence on the association between dietary nitrate and nitrite intake and cancer risk from published prospective and case-control studies. PubMed database was searched to identify eligible publications through April 30th, 2016. Study-specific relative risks (RRs) with corresponding 95% confidence interval (CI) from individual studies were pooled by using random- or fixed- model, and heterogeneity and publication bias analyses were conducted. Data from 62 observational studies, 49 studies for nitrates and 51 studies for nitrites, including a total of 60,627 cancer cases were analyzed. Comparing the highest vs. lowest levels, dietary nitrate intake was inversely associated with gastric cancer risk (RR = 0.78; 95%CI = 0.67-0.91) with moderate heterogeneity (I2 = 42.3%). In contrast, dietary nitrite intake was positively associated with adult glioma and thyroid cancer risk with pooled RR of 1.21 (95%CI = 1.03-1.42) and 1.52 (95%CI = 1.12-2.05), respectively. No significant associations were found between dietary nitrate/nitrite and cancers of the breast, bladder, colorectal, esophagus, renal cell, non-Hodgkin lymphoma, ovarian, and pancreas. The present meta-analysis provided modest evidence that positive associations of dietary nitrate and negative associations of dietary nitrite with certain cancers. PMID:27486968

  16. Meta-analysis of loci associated with age at natural menopause in African-American women

    Science.gov (United States)

    Chen, Christina T.L.; Liu, Ching-Ti; Chen, Gary K.; Andrews, Jeanette S.; Arnold, Alice M.; Dreyfus, Jill; Franceschini, Nora; Garcia, Melissa E.; Kerr, Kathleen F.; Li, Guo; Lohman, Kurt K.; Musani, Solomon K.; Nalls, Michael A.; Raffel, Leslie J.; Smith, Jennifer; Ambrosone, Christine B.; Bandera, Elisa V.; Bernstein, Leslie; Britton, Angela; Brzyski, Robert G.; Cappola, Anne; Carlson, Christopher S.; Couper, David; Deming, Sandra L.; Goodarzi, Mark O.; Heiss, Gerardo; John, Esther M.; Lu, Xiaoning; Le Marchand, Loic; Marciante, Kristin; Mcknight, Barbara; Millikan, Robert; Nock, Nora L.; Olshan, Andrew F.; Press, Michael F.; Vaiyda, Dhananjay; Woods, Nancy F.; Taylor, Herman A.; Zhao, Wei; Zheng, Wei; Evans, Michele K.; Harris, Tamara B.; Henderson, Brian E.; Kardia, Sharon L.R.; Kooperberg, Charles; Liu, Yongmei; Mosley, Thomas H.; Psaty, Bruce; Wellons, Melissa; Windham, Beverly G.; Zonderman, Alan B.; Cupples, L. Adrienne; Demerath, Ellen W.; Haiman, Christopher; Murabito, Joanne M.; Rajkovic, Aleksandar

    2014-01-01

    Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA. PMID:24493794

  17. Data Association at the Level of Narrative Plots to Support Analysis of Spatiotemporal Evolvement of Conflict: A Case Study in Nigeria

    Directory of Open Access Journals (Sweden)

    Size Bi

    2016-10-01

    Full Text Available Open data sources regarding conflicts are increasingly enriched by broad social media; these yield a volume of information that exceeds our process capabilities. One of the critical factors is that knowledge extraction from mixed data formats requires systematic, sophisticated modeling. Here, we propose using text mining modeling tools for building associations of heterogeneous semi-structured data to enhance decision-making. Using narrative plots, text representation, and cluster analysis, we provide a data association framework that can mine spatiotemporal data that occur in similar contexts. The framework contains the following steps: (1 a novel text representation is presented to vectorize the textual semantics by learning both co-word features and word orders in a unified form; (2 text clustering technology is employed to associate events of interest with similar events in historical logs, based solely on narrative plots of the events; and (3 the inferred activity procedure is visualized via an evolving spatiotemporal map through the Kriging algorithm. Our results demonstrate that the approach enables deeper discrimination into the trends underlying conflicts and possesses a narrative reasoning forward prediction with a precision of 0.4817, in addition to a high consistency with the conclusions of existing studies.

  18. Increased Eating Frequency Is Associated with Lower Obesity Risk, But Higher Energy Intake in Adults: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yue-Qiao Wang

    2016-06-01

    Full Text Available Body weight is regulated by energy intake which occurs several times a day in humans. In this meta-analysis, we evaluated whether eating frequency (EF is associated with obesity risk and energy intake in adults without any dietary restriction. Experimental and observational studies published before July 2015 were selected through English-language literature searches in several databases. These studies reported the association between EF and obesity risk (odd ratios, ORs in adults who were not in dietary restriction. R software was used to perform statistical analyses. Ten cross-sectional studies, consisting of 65,742 participants, were included in this analysis. ORs were considered as effect size for the analysis about the effect of EF on obesity risk. Results showed that the increase of EF was associated with 0.83 time lower odds of obesity (i.e., OR = 0.83, 95% confidence intervals (CI 0.70–0.99, p = 0.040. Analysis about the effect of EF on differences in participants’ energy intake revealed that increased EF was associated with higher energy intake (β = 125.36, 95% CI 21.76–228.97, p = 0.017. We conclude that increased EF may lead to lower obesity risk but higher energy intake. Clinical trials are warranted to confirm these results and to assess the clinical practice applicability.

  19. A Systematic Review and Meta-analysis of the Association Between Giardia lamblia and Endemic Pediatric Diarrhea in Developing Countries

    Science.gov (United States)

    Muhsen, Khitam; Levine, Myron M.

    2012-01-01

    We performed a systematic literature review and meta-analysis examining the association between diarrhea in young children in nonindustrialized settings and Giardia lamblia infection. Eligible were case/control and longitudinal studies that defined the outcome as acute or persistent (>14 days) diarrhea, adjusted for confounders and lasting for at least 1 year. Data on G. lamblia detection (mainly in stools) from diarrhea patients and controls without diarrhea were abstracted. Random effects model meta-analysis obtained pooled odds ratios (ORs) and 95% confidence intervals (CIs). Twelve nonindustrialized-setting acute pediatric diarrhea studies met the meta-analysis inclusion criteria. Random-effects model meta-analysis of combined results (9774 acute diarrhea cases and 8766 controls) yielded a pooled OR of 0.60 (95% CI, .38–.94; P = .03), indicating that G. lamblia was not associated with acute diarrhea. However, limited data suggest that initial Giardia infections in early infancy may be positively associated with diarrhea. Meta-analysis of 5 persistent diarrhea studies showed a pooled OR of 3.18 (95% CI, 1.50–6.76; P diarrhea in children in developing countries. PMID:23169940

  20. Smoking and caffeine consumption: a genetic analysis of their association.

    Science.gov (United States)

    Treur, Jorien L; Taylor, Amy E; Ware, Jennifer J; Nivard, Michel G; Neale, Michael C; McMahon, George; Hottenga, Jouke-Jan; Baselmans, Bart M L; Boomsma, Dorret I; Munafò, Marcus R; Vink, Jacqueline M

    2017-07-01

    Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta-analyses of genome-wide association studies on smoking and caffeine, the genetic correlation was calculated by LD-score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD-score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility. © 2016 The Authors.Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  1. The Association between Overweight and School Policies on Physical Activity: A Multilevel Analysis among Elementary School Youth in the PLAY-On Study

    Science.gov (United States)

    Leatherdale, Scott T.

    2010-01-01

    The objective is to examine school-level program and policy characteristics and student-level behavioural characteristics associated with being overweight. Multilevel logistic regression analysis were used to examine the school- and student-level characteristics associated with the odds of a student being overweight among 1264 Grade 5-8 students…

  2. Identification of Promising Mutants Associated with Egg Production Traits Revealed by Genome-Wide Association Study.

    Directory of Open Access Journals (Sweden)

    Jingwei Yuan

    Full Text Available Egg number (EN, egg laying rate (LR and age at first egg (AFE are important production traits related to egg production in poultry industry. To better understand the knowledge of genetic architecture of dynamic EN during the whole laying cycle and provide the precise positions of associated variants for EN, LR and AFE, laying records from 21 to 72 weeks of age were collected individually for 1,534 F2 hens produced by reciprocal crosses between White Leghorn and Dongxiang Blue-shelled chicken, and their genotypes were assayed by chicken 600 K Affymetrix high density genotyping arrays. Subsequently, pedigree and SNP-based genetic parameters were estimated and a genome-wide association study (GWAS was conducted on EN, LR and AFE. The heritability estimates were similar between pedigree and SNP-based estimates varying from 0.17 to 0.36. In the GWA analysis, we identified nine genome-wide significant loci associated with EN of the laying periods from 21 to 26 weeks, 27 to 36 weeks and 37 to 72 weeks. Analysis of GTF2A1 and CLSPN suggested that they influenced the function of ovary and uterus, and may be considered as relevant candidates. The identified SNP rs314448799 for accumulative EN from 21 to 40 weeks on chromosome 5 created phenotypic differences of 6.86 eggs between two homozygous genotypes, which could be potentially applied to the molecular breeding for EN selection. Moreover, our finding showed that LR was a moderate polygenic trait. The suggestive significant region on chromosome 16 for AFE suggested the relationship between sex maturity and immune in the current population. The present study comprehensively evaluates the role of genetic variants in the development of egg laying. The findings will be helpful to investigation of causative genes function and future marker-assisted selection and genomic selection in chickens.

  3. Association of ESRα Gene Pvu II T>C, XbaI A>G and BtgI G>A Polymorphisms with Knee Osteoarthritis Susceptibility: A Systematic Review and Meta-Analysis Based on 22 Case-Control Studies.

    Science.gov (United States)

    Yazdi, Masoud Mahdinezhad; Jamalaldini, Mohamad H; Sobhan, Mohammad R; Jafari, Mohammadali; Mazaheri, Mahta; Zare-Shehneh, Masoud; Neamatzadeh, Hossein

    2017-11-01

    Many studies have reported the association of estrogen receptor α gene (ESRα) ESRα PvuII T>C, XbaI A>G and BtgI G>A polymorphisms with Knee osteoarthritis (KOA) risk, but the results remained controversial. In order to drive a more precise estimation, the present systematic review and meta-analysis was performed to investigate the association between ESRα polymorphisms and KOA susceptibility. Eligible articles were identified by search of databases including PubMed, ISI Web of Knowledge and Google scholar up to March 1, 2017. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. A total of 22 case-control studies in eleven publications with 6,575 KOA cases and 7,459 controls were included in the meta-analysis. By pooling all the studies, either ESRα PvuII T>C and XbaI A>G polymorphisms was not associated with KOA risk in the overall population. However, ESRα BtgI G>A was significantly associated with KOA risk under all five genetic models. In the subgroup analysis by ethnicity, a significant association was observed between ESRα PvuII T>C polymorphism and KOA risk in Asians under heterozygote model. In addition, significant association was found between ESRα XbaI A>G polymorphism and KOA in Caucasians under allelic, homozygote, dominant and recessive models. The present meta-analysis suggests that ESRα BtgI G>A rather than ESRα PvuII T>C and XbaI A>G polymorphisms is associated with an increased KOA risk in overall population. Moreover, we have found that ESRα PvuII T>C and XbaI A>G polymorphisms associated with KOA susceptibility by ethnicity backgrounds.

  4. Association of ESRα Gene Pvu II T>C, XbaI A>G and BtgI G>A Polymorphisms with Knee Osteoarthritis Susceptibility: A Systematic Review and Meta-Analysis Based on 22 Case-Control Studies

    Directory of Open Access Journals (Sweden)

    Masoud Mehdinejad Yazdi

    2017-11-01

    Full Text Available Background: Many studies have reported the association of estrogen receptor α gene (ESRα ESRα PvuII T>C, XbaI A>G and BtgI G>A polymorphisms with Knee osteoarthritis (KOA risk, but the results remained controversial. In order to drive a more precise estimation, the present systematic review and meta-analysis was performed to investigate the association between ESRα polymorphisms and KOA susceptibility. Methods: Eligible articles were identified by search of databases including PubMed, ISI Web of Knowledge and Google scholar up to March 1, 2017. Data were extracted by two independent authors and pooled odds ratio (OR with 95% confidence interval (CI was calculated. Results: A total of 22 case-control studies in eleven publications with 6,575 KOA cases and 7,459 controls were included in the meta-analysis. By pooling all the studies, either ESRα PvuII T>C and XbaI A>G polymorphisms was not associated with KOA risk in the overall population. However, ESRα BtgI G>A was significantly associated with KOA risk under all five genetic models. In the subgroup analysis by ethnicity, a significant association was observed between ESRα PvuII T>C polymorphism and KOA risk in Asians under heterozygote model. In addition, significant association was found between ESRα XbaI A>G polymorphism and KOA in Caucasians under allelic, homozygote, dominant and recessive models. Conclusion: The present meta-analysis suggests that ESRα BtgI G>A rather than ESRα PvuII T>C and XbaI A>G polymorphisms is associated with an increased KOA risk in overall population. Moreover, we have found that ESRα PvuII T>C and XbaI A>G polymorphisms associated with KOA susceptibility by ethnicity backgrounds.

  5. Analysis of symptoms and their potential associations with e-liquids' components: a social media study.

    Science.gov (United States)

    Li, Qiudan; Zhan, Yongcheng; Wang, Lei; Leischow, Scott J; Zeng, Daniel Dajun

    2016-07-30

    The electronic cigarette (e-cigarette) market has grown rapidly in recent years. However, causes of e-cigarette related symptoms among users and their impact on health remain uncertain. This research aims to mine the potential relationships between symptoms and e-liquid components, such as propylene glycol (PG), vegetable glycerine (VG), flavor extracts, and nicotine, using user-generated data collected from Reddit. A total of 3605 e-liquid related posts from January 1st, 2011 to June 30th, 2015 were collected from Reddit. Then the patterns of VG/PG distribution among different flavors were analyzed. Next, the relationship between throat hit, which was a typical symptom of e-cigarette use, and e-liquid components was studied. Finally, other symptoms were examined based on e-liquid components and user sentiment. We discovered 3 main sets of findings: 1) We identified three groups of flavors in terms of VG/PG ratios. Fruits, cream, and nuts flavors were similar. Sweet, menthol, and seasonings flavors were classified into one group. Tobacco and beverages flavors were the third group. 2) Throat hit was analyzed and we found that menthol and tobacco flavors, as well as high ratios of PG and nicotine level, could produce more throat hit. 3) A total of 9 systems of 25 symptoms were identified and analyzed. Components including VG/PG ratio, flavor, and nicotine could be possible reasons for these symptoms. E-liquid components shown to be associated with e-cigarette use symptomology were VG/PG ratios, flavors, and nicotine levels. Future analysis could be conducted based on the structure of e-liquid components categories built in this study. Information revealed in this study could be utilized by e-cigarette users to understand the relationship between e-liquid type and symptoms experienced, by vendors to choose appropriate recipes of e-liquid, and by policy makers to develop new regulations.

  6. Auditory vocal analysis and factors associated with voice disorders among teachers.

    Science.gov (United States)

    de Ceballos, Albanita Gomes da Costa; Carvalho, Fernando Martins; de Araújo, Tânia Maria; Dos Reis, Eduardo José Farias Borges

    2011-06-01

    Teachers are professionals who demand much of their voices and, consequently, present a high risk of developing vocal disorders during the course of employment. To identify factors associated with vocal disorders among teachers. An exploratory cross-sectional study, which investigated 476 teachers in primary and secondary schools in the city of Salvador, Bahia. Teachers answered a questionnaire and were submitted to auditory vocal analysis. The GRBAS was used for the diagnosis of vocal disorders. The study population comprised 82.8% women, teachers with an average age of 40.7 years, teachers with higher education (88.4%), with an average workday of 38 hours per week, average 11.5 years of professional practice and average monthly income of R$1.817.18. The prevalence of voice disorders was 53.6%. (255 teachers). The bivariate analysis showed statistically significant associations between vocal disorders and age above 40 years (PR = 1.83; 95% CI; 1.27-2.64), family history of dysphonia (PR = 1.72; 95% CI; 1.06-2.80), over 20 hours of weekly working hours (PR = 1.66; 95% CI; 1.09-2.52) and presence of chalk dust in the classroom (PR = 1.70; 95% CI; 1.14-2.53). The study concluded that teachers, 40 years old and over, with a family history of dysphonia, working over 20 hours weekly, and teaching in classrooms with chalk dust are more likely to develop voice disorders than others.

  7. Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication.

    Directory of Open Access Journals (Sweden)

    Saimul Islam

    Full Text Available Human papillomavirus (HPV causes tumors primarily Cervical cancer. Recently, inconsistent reports came up in Breast cancer (BC too. In India, despite treatment 70,218 BC patients die each year. So, we explored the association of HPV, if any, with BC prognosis in Indian pre-therapeutic (PT and Neo-adjuvant chemotherapy (NACT patients with subsequent analysis of HPV profile.HPV prevalence was checked and analysis of physical status, copy number, genome variation, promoter methylation and expression (mRNA and protein of the prevalent subtype was done.High prevalence of HPV was observed in both PT (64.0% and NACT (71.0% cases with significant association with younger (20-45 yrs PT patients. Interestingly, HPV infection was significantly increased from adjacent normal breast (9.5%, 2/21, fibro adenomas (30%, 3/10 to tumors (64.8%, 203/313 samples. In both PT and NACT cases, HPV16 was the most prevalent subtype (69.0% followed by HPV18 and HPV33. Survival analysis illustrated hrHPV infected PT patients had worst prognosis. So, detailed analysis of HPV16 profile was done which showed Europian-G350 as the most frequent HPV16 variant along with high rate of integration. Moreover, low copy number and hyper-methylation of P97 early promoter were concordant with low HPV16 E6 and E7 mRNA and protein expression. Notably, four novel variations (KT020838, KT020840, KT020841 and KT020839 in the LCR region and two (KT020836 and KT020837 in the E6 region were identified for the first time along with two novel E6^E7*I (KU199314 and E6^E7*II (KU199315 fusion transcript variants.Thus, significant association of hrHPV with prognosis of Indian BC patients led to additional investigation of HPV16 profile. Outcomes indicated a plausible role of HPV in Indian BC patients.

  8. Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.

    Science.gov (United States)

    Broce, Iris; Karch, Celeste M; Wen, Natalie; Fan, Chun C; Wang, Yunpeng; Tan, Chin Hong; Kouri, Naomi; Ross, Owen A; Höglinger, Günter U; Muller, Ulrich; Hardy, John; Momeni, Parastoo; Hess, Christopher P; Dillon, William P; Miller, Zachary A; Bonham, Luke W; Rabinovici, Gil D; Rosen, Howard J; Schellenberg, Gerard D; Franke, Andre; Karlsen, Tom H; Veldink, Jan H; Ferrari, Raffaele; Yokoyama, Jennifer S; Miller, Bruce L; Andreassen, Ole A; Dale, Anders M; Desikan, Rahul S; Sugrue, Leo P

    2018-01-01

    Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate enriched in microglia/macrophages compared to other central nervous system cell types. The main study limitation is that the results represent only clinically diagnosed individuals. Also, given the complex interconnectedness of the HLA region, we were not able to define the specific gene or genes on Chr 6 responsible for our pleiotropic signal. We

  9. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

    Science.gov (United States)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara; Canisius, Sander; Dennis, Joe; Lush, Michael J; Maranian, Mel J; Bolla, Manjeet K; Wang, Qin; Shah, Mitul; Perkins, Barbara J; Czene, Kamila; Eriksson, Mikael; Darabi, Hatef; Brand, Judith S; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Nielsen, Sune F; Rahman, Nazneen; Turnbull, Clare; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos-Santos-Silva, Isabel; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Eilber, Ursula; Behrens, Sabine; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Aaltonen, Kirsimari; Ahsan, Habibul; Kibriya, Muhammad G; Whittemore, Alice S; John, Esther M; Malone, Kathleen E; Gammon, Marilie D; Santella, Regina M; Ursin, Giske; Makalic, Enes; Schmidt, Daniel F; Casey, Graham; Hunter, David J; Gapstur, Susan M; Gaudet, Mia M; Diver, W Ryan; Haiman, Christopher A; Schumacher, Fredrick; Henderson, Brian E; Le Marchand, Loic; Berg, Christine D; Chanock, Stephen J; Figueroa, Jonine; Hoover, Robert N; Lambrechts, Diether; Neven, Patrick; Wildiers, Hans; van Limbergen, Erik; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A; van der Luijt, Rob B; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Yoo, Keun-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Guénel, Pascal; Truong, Thérèse; Mulot, Claire; Sanchez, Marie; Burwinkel, Barbara; Marme, Frederik; Surowy, Harald; Sohn, Christof; Wu, Anna H; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O; González-Neira, Anna; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Lindblom, Annika; Margolin, Sara; Teo, Soo Hwang; Yip, Cheng Har; Taib, Nur Aishah Mohd; Tan, Gie-Hooi; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John W M; Collée, J Margriet; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Apicella, Carmel; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Kristensen, Vessela N; Nord, Silje; Alnaes, Grethe I Grenaker; Giles, Graham G; Milne, Roger L; McLean, Catriona; Canzian, Federico; Trichopoulos, Dimitrios; Peeters, Petra; Lund, Eiliv; Sund, Malin; Khaw, Kay-Tee; Gunter, Marc J; Palli, Domenico; Mortensen, Lotte Maxild; Dossus, Laure; Huerta, Jose-Maria; Meindl, Alfons; Schmutzler, Rita K; Sutter, Christian; Yang, Rongxi; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Chan, Ching Wan; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Haeberle, Lothar; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; Swerdlow, Anthony J; Brinton, Louise; Garcia-Closas, Montserrat; Zheng, Wei; Halverson, Sandra L; Shrubsole, Martha; Long, Jirong; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Bogdanova, Natalia V; Dörk, Thilo; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Huzarski, Tomasz; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Kabisch, Maria; Torres, Diana; Neuhausen, Susan L; Anton-Culver, Hoda; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Simard, Jacques; Pharoah, Paul P D P; Kraft, Peter; Dunning, Alison M; Chenevix-Trench, Georgia; Hall, Per; Easton, Douglas F

    2015-04-01

    Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

  10. Is good insight associated with depression among patients with schizophrenia? Systematic review and meta-analysis.

    Science.gov (United States)

    Belvederi Murri, Martino; Respino, Matteo; Innamorati, Marco; Cervetti, Alice; Calcagno, Pietro; Pompili, Maurizio; Lamis, Dorian A; Ghio, Lucio; Amore, Mario

    2015-03-01

    Among patients with schizophrenia, better insight may be associated with depression, but the findings on this issue are mixed. We examined the association between insight and depression in schizophrenia by conducting a systematic review and meta-analysis. The meta-analysis was based on 59 correlational studies and showed that global clinical insight was associated weakly, but significantly with depression (effect size r=0.14), as were the insight into the mental disorder (r=0.14), insight into symptoms (r=0.14), and symptoms' attributions (r=0.17). Conversely, neither insight into the social consequences of the disorder nor into the need for treatment was associated with symptoms of depression. Better cognitive insight was significantly associated with higher levels of depression. The exploratory meta-regression showed that methodological factors (e.g. the instrument used to assess depression and the phase of the illness) can significantly influence the magnitude of the association between insight and depression. Moreover, results from longitudinal studies suggest that the relation between insight and depression might be stronger than what is observed at the cross-sectional level. Finally, internalized stigma, illness perception, recovery attitudes, ruminative style, and premorbid adjustment seem to be relevant moderators and/or mediators of the association between insight and depression. In conclusion, literature indicates that among patients with schizophrenia, better insight is associated with higher levels of depressive symptoms. Thus, interventions aimed at promoting patients' insight should take into account the clinical implications of these findings. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

    DEFF Research Database (Denmark)

    Demenais, Florence; Margaritte-Jeannin, Patricia; Barnes, Kathleen C

    2018-01-01

    We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known...

  12. Molecular genetic studies in Saudi population; identified variants from GWAS and meta-analysis in stroke.

    Science.gov (United States)

    Alharbi, Khalid Khalaf; Ali Khan, Imran; Alotaibi, Mohammad Abdullah; Saud Aloyaid, Abdullah; Al-Basheer, Haifa Abdulaziz; Alghamdi, Naelah Abdullah; Al-Baradie, Raid Saleem; Al-Sulaiman, A M

    2018-01-01

    Stroke is a multifactorial and heterogeneous disorder, correlates with heritability and considered as one of the major diseases. The prior reports performed the variable models such as genome-wide association studies (GWAS), replication, case-control, cross-sectional and meta-analysis studies and still, we lack diagnostic marker in the global world. There are limited studies were carried out in Saudi population, and we aim to investigate the molecular association of single nucleotide polymorphisms (SNPs) identified through GWAS and meta-analysis studies in stroke patients in the Saudi population. In this case-control study, we have opted gender equality of 207 cases and 207 controls from the capital city of Saudi Arabia in King Saud University Hospital. The peripheral blood (5 ml) sample will be collected in two different vacutainers, and three mL of the coagulated blood will be used for lipid analysis (biochemical tests) and two mL will be used for DNA analysis (molecular tests). Genomic DNA will be extracted with the collected blood samples, and specific primers will be designed for the opted SNPs ( SORT1 -rs646218 and OLR1 -rs11053646 polymorphisms) and PCR-RFLP will be performed and randomly DNA sequencing will be carried out to cross check the results. The rs646218 and rs11053646 polymorphisms were significantly associated with allele, genotype and dominant models with and without crude odds ratios (OR's) and Multiple logistic regression analysis (p Saudi population. The current results were in the association with the prior study results documented through GWAS and meta-analysis association. However, other ethnic population studies should be performed to rule out in the human hereditary diseases.

  13. Genomic and Metagenomic Analysis of Diversity-Generating Retroelements Associated with Treponema denticola

    Directory of Open Access Journals (Sweden)

    Sutichot eNimkulrat

    2016-06-01

    Full Text Available Diversity-generating retroelements (DGRs are genetic cassettes that can produce massive protein sequence variation in prokaryotes. Presumably DGRs confer selective advantages to their hosts (bacteria or viruses by generating variants of target genes—typically resulting in target proteins with altered ligand-binding specificity—through a specialized error-prone reverse transcription process. The only extensively studied DGR system is from the Bordetella phage BPP-1, although DGRs are predicted to exist in other species. Using bioinformatics analysis, we discovered that the DGR system associated with the Treponema denticola species (a human oral-associated periopathogen is dynamic (with gains/losses of the system found in the isolates and diverse (with multiple types found in isolated genomes and the human microbiota. The T. denticola DGR is found in only nine of the 17 sequenced T. denticola strains. Analysis of the DGR-associated template regions and reverse transcriptase gene sequences revealed two types of DGR systems in T. denticola: the ATCC35405-type shared by seven isolates including ATCC35405; and the SP32-type shared by two isolates (SP32 and SP33, suggesting multiple DGR acquisitions. We detected additional variants of the T. denticola DGR systems in the human microbiomes, and found that the SP32-type DGR is more abundant than the ATCC35405-type in the healthy human oral microbiome, although the latter is found in more sequenced isolates. This is the first comprehensive study to characterize the DGRs associated with T. denticola in individual genomes as well as human microbiomes, demonstrating the importance of utilizing both individual genomes and metagenomes for characterizing the elements, and for analyzing their diversity and distribution in human populations.

  14. A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study

    Directory of Open Access Journals (Sweden)

    Han Thang S

    2011-01-01

    Full Text Available Abstract Background A number of single nucleotide polymorphisms (SNPs have been associated with broadband ultrasound attenuation (BUA and speed of sound (SOS as measured by quantitative ultrasound (QUS at the calcaneus in the Framingham 100K genome-wide association study (GWAS but have not been validated in independent studies. The aim of this analysis was to determine if these SNPs are associated with QUS measurements assessed in a large independent population of European middle-aged and elderly men. The association between these SNPs and bone mineral density (BMD measured using dual-energy X-ray absorptiometry (DXA was also tested. Methods Men aged 40-79 years (N = 2960 were recruited from population registers in seven European centres for participation in an observational study of male ageing, the European Male Ageing Study (EMAS. QUS at the calcaneus was measured in all subjects and blood was taken for genetic analysis. Lumbar spine (LS, femoral neck (FN and total hip (TH BMD were measured by DXA in a subsample of 620 men in two centres. SNPs associated with BUA or SOS in the Framingham study with p -4 were selected and genotyped using SEQUENOM technology. Linear regression was used to test for the association between SNPs and standardised (SD bone outcomes under an additive genetic model adjusting for centre. The same direction of effect and p Results Thirty-four of 38 selected SNPs were successfully genotyped in 2377 men. Suggestive evidence of replication was observed for a single SNP, rs3754032, which was associated with a higher SOS (β(SD = 0.07, p = 0.032 but not BUA (β(SD = 0.02, p = 0.505 and is located in the 3'UTR of WDR77 (WD repeat domain 77 also known as androgen receptor cofactor p44. A single SNP, rs238358, was associated with BMD at the LS (β(SD = -0.22, p = 0.014, FN (β(SD = -0.31,p = 0.001 and TH (β(SD = -0.36, p = 0.002 in a locus previously associated with LS BMD in large-scale GWAS, incorporating AKAP11 and RANKL

  15. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    Science.gov (United States)

    Felix, Janine F.; Bradfield, Jonathan P.; Monnereau, Claire; van der Valk, Ralf J.P.; Stergiakouli, Evie; Chesi, Alessandra; Gaillard, Romy; Feenstra, Bjarke; Thiering, Elisabeth; Kreiner-Møller, Eskil; Mahajan, Anubha; Pitkänen, Niina; Joro, Raimo; Cavadino, Alana; Huikari, Ville; Franks, Steve; Groen-Blokhuis, Maria M.; Cousminer, Diana L.; Marsh, Julie A.; Lehtimäki, Terho; Curtin, John A.; Vioque, Jesus; Ahluwalia, Tarunveer S.; Myhre, Ronny; Price, Thomas S.; Vilor-Tejedor, Natalia; Yengo, Loïc; Grarup, Niels; Ntalla, Ioanna; Ang, Wei; Atalay, Mustafa; Bisgaard, Hans; Blakemore, Alexandra I.; Bonnefond, Amelie; Carstensen, Lisbeth; Eriksson, Johan; Flexeder, Claudia; Franke, Lude; Geller, Frank; Geserick, Mandy; Hartikainen, Anna-Liisa; Haworth, Claire M.A.; Hirschhorn, Joel N.; Hofman, Albert; Holm, Jens-Christian; Horikoshi, Momoko; Hottenga, Jouke Jan; Huang, Jinyan; Kadarmideen, Haja N.; Kähönen, Mika; Kiess, Wieland; Lakka, Hanna-Maaria; Lakka, Timo A.; Lewin, Alexandra M.; Liang, Liming; Lyytikäinen, Leo-Pekka; Ma, Baoshan; Magnus, Per; McCormack, Shana E.; McMahon, George; Mentch, Frank D.; Middeldorp, Christel M.; Murray, Clare S.; Pahkala, Katja; Pers, Tune H.; Pfäffle, Roland; Postma, Dirkje S.; Power, Christine; Simpson, Angela; Sengpiel, Verena; Tiesler, Carla M. T.; Torrent, Maties; Uitterlinden, André G.; van Meurs, Joyce B.; Vinding, Rebecca; Waage, Johannes; Wardle, Jane; Zeggini, Eleftheria; Zemel, Babette S.; Dedoussis, George V.; Pedersen, Oluf; Froguel, Philippe; Sunyer, Jordi; Plomin, Robert; Jacobsson, Bo; Hansen, Torben; Gonzalez, Juan R.; Custovic, Adnan; Raitakari, Olli T.; Pennell, Craig E.; Widén, Elisabeth; Boomsma, Dorret I.; Koppelman, Gerard H.; Sebert, Sylvain; Järvelin, Marjo-Riitta; Hyppönen, Elina; McCarthy, Mark I.; Lindi, Virpi; Harri, Niinikoski; Körner, Antje; Bønnelykke, Klaus; Heinrich, Joachim; Melbye, Mads; Rivadeneira, Fernando; Hakonarson, Hakon; Ring, Susan M.; Smith, George Davey; Sørensen, Thorkild I.A.; Timpson, Nicholas J.; Grant, Struan F.A.; Jaddoe, Vincent W.V.

    2016-01-01

    A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10−8) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10−10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index. PMID:26604143

  16. Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2.

    Science.gov (United States)

    Cheng, Yu-Ching; Stanne, Tara M; Giese, Anne-Katrin; Ho, Weang Kee; Traylor, Matthew; Amouyel, Philippe; Holliday, Elizabeth G; Malik, Rainer; Xu, Huichun; Kittner, Steven J; Cole, John W; O'Connell, Jeffrey R; Danesh, John; Rasheed, Asif; Zhao, Wei; Engelter, Stefan; Grond-Ginsbach, Caspar; Kamatani, Yoichiro; Lathrop, Mark; Leys, Didier; Thijs, Vincent; Metso, Tiina M; Tatlisumak, Turgut; Pezzini, Alessandro; Parati, Eugenio A; Norrving, Bo; Bevan, Steve; Rothwell, Peter M; Sudlow, Cathie; Slowik, Agnieszka; Lindgren, Arne; Walters, Matthew R; Jannes, Jim; Shen, Jess; Crosslin, David; Doheny, Kimberly; Laurie, Cathy C; Kanse, Sandip M; Bis, Joshua C; Fornage, Myriam; Mosley, Thomas H; Hopewell, Jemma C; Strauch, Konstantin; Müller-Nurasyid, Martina; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Meisinger, Christine; Ikram, M Arfan; Longstreth, W T; Meschia, James F; Seshadri, Sudha; Sharma, Pankaj; Worrall, Bradford; Jern, Christina; Levi, Christopher; Dichgans, Martin; Boncoraglio, Giorgio B; Markus, Hugh S; Debette, Stephanie; Rolfs, Arndt; Saleheen, Danish; Mitchell, Braxton D

    2016-02-01

    Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset genetic variants at loci with association Pstroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2. HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke. © 2016 American Heart Association, Inc.

  17. Associations of Parenting Dimensions and Styles with Externalizing Problems of Children and Adolescents: An Updated Meta-Analysis

    Science.gov (United States)

    Pinquart, Martin

    2017-01-01

    The present meta-analysis integrates research from 1,435 studies on associations of parenting dimensions and styles with externalizing symptoms in children and adolescents. Parental warmth, behavioral control, autonomy granting, and an authoritative parenting style showed very small to small negative concurrent and longitudinal associations with…

  18. Hyperuricemia and associated factors: a cross-sectional study of Japanese-Brazilians

    Directory of Open Access Journals (Sweden)

    Juliana Poletto

    2011-02-01

    Full Text Available This cross-sectional study aimed to estimate the prevalence of hyperuricemia and associated risk factors among Japanese-Brazilians. We obtained data on demographic, health history, food intake, and laboratory variables. Chi-square and prevalence ratios were used as measures of association. 35.3% of the subjects presented hyperuricemia, which was more frequent in smokers, males, age > 55 years, with co-morbidities, individuals on uric acid-increasing medication, serum creatinine > 1.4mg/dL, high alcohol consumption, and low consumption of milk and dairy products. In the multivariate analysis, the associations remained significant with gender, overweight, central obesity, hypertriglyceridemia, and use of specific drugs. Among males, low intake of saturated fat was associated with hyperuricemia. Individuals with hypertension showed a negative association with dairy product consumption. The high hyperuricemia prevalence suggests that changes in nutritional profile and control of associated co-morbidities could help minimize occurrence of this condition.

  19. Analysis of pharmacogenomic variants associated with population differentiation.

    Directory of Open Access Journals (Sweden)

    Bora Yeon

    Full Text Available In the present study, we systematically investigated population differentiation of drug-related (DR genes in order to identify common genetic features underlying population-specific responses to drugs. To do so, we used the International HapMap project release 27 Data and Pharmacogenomics Knowledge Base (PharmGKB database. First, we compared four measures for assessing population differentiation: the chi-square test, the analysis of variance (ANOVA F-test, Fst, and Nearest Shrunken Centroid Method (NSCM. Fst showed high sensitivity with stable specificity among varying sample sizes; thus, we selected Fst for determining population differentiation. Second, we divided DR genes from PharmGKB into two groups based on the degree of population differentiation as assessed by Fst: genes with a high level of differentiation (HD gene group and genes with a low level of differentiation (LD gene group. Last, we conducted a gene ontology (GO analysis and pathway analysis. Using all genes in the human genome as the background, the GO analysis and pathway analysis of the HD genes identified terms related to cell communication. "Cell communication" and "cell-cell signaling" had the lowest Benjamini-Hochberg's q-values (0.0002 and 0.0006, respectively, and "drug binding" was highly enriched (16.51 despite its relatively high q-value (0.0142. Among the 17 genes related to cell communication identified in the HD gene group, five genes (STX4, PPARD, DCK, GRIK4, and DRD3 contained single nucleotide polymorphisms with Fst values greater than 0.5. Specifically, the Fst values for rs10871454, rs6922548, rs3775289, rs1954787, and rs167771 were 0.682, 0.620, 0.573, 0.531, and 0.510, respectively. In the analysis using DR genes as the background, the HD gene group contained six significant terms. Five were related to reproduction, and one was "Wnt signaling pathway," which has been implicated in cancer. Our analysis suggests that the HD gene group from PharmGKB is

  20. Analysis of pharmacogenomic variants associated with population differentiation.

    Science.gov (United States)

    Yeon, Bora; Ahn, Eunyong; Kim, Kyung-Im; Kim, In-Wha; Oh, Jung Mi; Park, Taesung

    2015-01-01

    In the present study, we systematically investigated population differentiation of drug-related (DR) genes in order to identify common genetic features underlying population-specific responses to drugs. To do so, we used the International HapMap project release 27 Data and Pharmacogenomics Knowledge Base (PharmGKB) database. First, we compared four measures for assessing population differentiation: the chi-square test, the analysis of variance (ANOVA) F-test, Fst, and Nearest Shrunken Centroid Method (NSCM). Fst showed high sensitivity with stable specificity among varying sample sizes; thus, we selected Fst for determining population differentiation. Second, we divided DR genes from PharmGKB into two groups based on the degree of population differentiation as assessed by Fst: genes with a high level of differentiation (HD gene group) and genes with a low level of differentiation (LD gene group). Last, we conducted a gene ontology (GO) analysis and pathway analysis. Using all genes in the human genome as the background, the GO analysis and pathway analysis of the HD genes identified terms related to cell communication. "Cell communication" and "cell-cell signaling" had the lowest Benjamini-Hochberg's q-values (0.0002 and 0.0006, respectively), and "drug binding" was highly enriched (16.51) despite its relatively high q-value (0.0142). Among the 17 genes related to cell communication identified in the HD gene group, five genes (STX4, PPARD, DCK, GRIK4, and DRD3) contained single nucleotide polymorphisms with Fst values greater than 0.5. Specifically, the Fst values for rs10871454, rs6922548, rs3775289, rs1954787, and rs167771 were 0.682, 0.620, 0.573, 0.531, and 0.510, respectively. In the analysis using DR genes as the background, the HD gene group contained six significant terms. Five were related to reproduction, and one was "Wnt signaling pathway," which has been implicated in cancer. Our analysis suggests that the HD gene group from PharmGKB is associated with

  1. Meta-analysis of sequence-based association studies across three cattle breeds reveals 25 QTL for fat and protein percentages in milk at nucleotide resolution.

    Science.gov (United States)

    Pausch, Hubert; Emmerling, Reiner; Gredler-Grandl, Birgit; Fries, Ruedi; Daetwyler, Hans D; Goddard, Michael E

    2017-11-09

    Genotyping and whole-genome sequencing data have been generated for hundreds of thousands of cattle. International consortia used these data to compile imputation reference panels that facilitate the imputation of sequence variant genotypes for animals that have been genotyped using dense microarrays. Association studies with imputed sequence variant genotypes allow for the characterization of quantitative trait loci (QTL) at nucleotide resolution particularly when individuals from several breeds are included in the mapping populations. We imputed genotypes for 28 million sequence variants in 17,229 cattle of the Braunvieh, Fleckvieh and Holstein breeds in order to compile large mapping populations that provide high power to identify QTL for milk production traits. Association tests between imputed sequence variant genotypes and fat and protein percentages in milk uncovered between six and thirteen QTL (P < 1e-8) per breed. Eight of the detected QTL were significant in more than one breed. We combined the results across breeds using meta-analysis and identified a total of 25 QTL including six that were not significant in the within-breed association studies. Two missense mutations in the ABCG2 (p.Y581S, rs43702337, P = 4.3e-34) and GHR (p.F279Y, rs385640152, P = 1.6e-74) genes were the top variants at QTL on chromosomes 6 and 20. Another known causal missense mutation in the DGAT1 gene (p.A232K, rs109326954, P = 8.4e-1436) was the second top variant at a QTL on chromosome 14 but its allelic substitution effects were inconsistent across breeds. It turned out that the conflicting allelic substitution effects resulted from flaws in the imputed genotypes due to the use of a multi-breed reference population for genotype imputation. Many QTL for milk production traits segregate across breeds and across-breed meta-analysis has greater power to detect such QTL than within-breed association testing. Association testing between imputed sequence variant genotypes and

  2. The Association of Digit Ratio (2D : 4D) with Cancer: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Bunevicius, Adomas

    2018-01-01

    Intrauterine sex hormone environment as indicated by the second to the fourth digit ratio (2D : 4D) can be associated with cancer risk. This systematic review and meta-analysis aimed to evaluate the association of 2D : 4D with cancer diagnosis, malignancy, and age at presentation. Studies that evaluated the association of 2D : 4D with cancer risk were collected from Pubmed/MEDLINE and Clarivate Analytics databases. Nineteen studies were included in the qualitative analysis. The 2D : 4D ratio was studied in prostate cancer, breast cancer, testicular cancer, gastric cancer, oral cancer, brain tumors, and cervical intraepithelial neoplasia. Low 2D : 4D was associated with prostate cancer, gastric cancer, and brain tumors, while high 2D : 4D, with breast cancer risk and cervical dysplasia. The 2D : 4D ratio was not associated with prostate, breast, and gastric cancer stage. Greater 2D : 4D ratio was associated with younger presentation of breast cancer and brain tumors. The meta-analyses demonstrated that testicular cancer was not associated with right-hand 2D : 4D ratio ( p = 0.74) and gastric cancer was not associated with right-hand ( p = 0.15) and left-hand ( p = 0.95) 2D : 4D ratio. Sex hormone environment during early development is associated with cancer risk later in life. Further studies exploring the link between intrauterine hormone environment and cancer risk are encouraged.

  3. Large scale association analysis identifies three susceptibility loci for coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Stephanie Saade

    Full Text Available Genome wide association studies (GWAS and their replications that have associated DNA variants with myocardial infarction (MI and/or coronary artery disease (CAD are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3, and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR=0.68, p=0.0035, while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR=1.33, p=0.0086. Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology.

  4. Associations of rotational shift work and night shift status with hypertension: a systematic review and meta-analysis.

    Science.gov (United States)

    Manohar, Sandhya; Thongprayoon, Charat; Cheungpasitporn, Wisit; Mao, Michael A; Herrmann, Sandra M

    2017-10-01

    The reported risks of hypertension (HTN) in rotating shift and night shift workers are controversial. The objective of this meta-analysis was to assess the association between shift work status and HTN. A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception through October 2016. Studies that reported odds ratios (OR) comparing the risk of HTN in shift workers were included. A prespecified subgroup analysis by rotating shift and night shift statuses were also performed. Pooled OR and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. The protocol for this study is registered with International Prospective Register of Systematic Reviews; no. CRD42016051843. Twenty-seven observational studies (nine cohort and 18 cross-sectional studies) with a total of 394 793 individuals were enrolled. The pooled ORs of HTN in shift workers in cohort and cross-sectional studies were 1.31 (95% CI, 1.07-1.60) and 1.10 (95% CI, 1.00-1.20), respectively. When meta-analysis was restricted only to cohort studies in rotating shift, the pooled OR of HTN in rotating shift workers was 1.34 (95% CI, 1.08-1.67). The data regarding night shift and HTN in cohort studies was limited. The pooled OR of HTN in night shift workers in cross-sectional studies was 1.07 (95% CI, 0.85-1.35). Based on the findings of our meta-analysis, shiftwork status may play an important role in HTN, as there is a significant association between rotating shift work and HTN. However, there is no significant association between night shift status and risk of HTN.

  5. Factors associated with survival of epiploic foramen entrapment colic: a multicentre, international study.

    Science.gov (United States)

    Archer, D C; Pinchbeck, G L; Proudman, C J

    2011-08-01

    Epiploic foramen entrapment (EFE) has been associated with reduced post operative survival compared to other types of colic but specific factors associated with reduced long-term survival of these cases have not been evaluated in a large number of horses using survival analysis. To describe post operative survival of EFE cases and to identify factors associated with long-term survival. A prospective, multicentre, international study was conducted using clinical data and long-term follow-up information for 126 horses diagnosed with EFE during exploratory laparotomy at 15 clinics in the UK, Ireland and USA. Descriptive data were generated and survival analysis performed to identify factors associated with reduced post operative survival. For the EFE cohort that recovered following anaesthesia, survival to hospital discharge was 78.5%. Survival to 1 and 2 years post operatively was 50.6 and 34.3%, respectively. The median survival time of EFE cases undergoing surgery was 397 days. Increased packed cell volume (PCV) and increased length of small intestine (SI) resected were significantly associated with increased likelihood of mortality when multivariable analysis of pre- and intraoperative variables were analysed. When all pre-, intra- and post operative variables were analysed separately, only horses that developed post operative ileus (POI) were shown to be at increased likelihood of mortality. Increased PCV, increased length of SI resected and POI are all associated with increased likelihood of mortality of EFE cases. This emphasises the importance of early diagnosis and treatment and the need for improved strategies in the management of POI in order to reduce post operative mortality in these cases. The present study provides evidence-based information to clinicians and owners of horses undergoing surgery for EFE about long-term survival. These results are applicable to university and large private clinics over a wide geographical area. © 2011 EVJ Ltd.

  6. Association of vitamin D receptor BsmI, TaqI, FokI, and ApaI polymorphisms with susceptibility of chronic periodontitis: A systematic review and meta-analysis based on 38 case -control studies.

    Science.gov (United States)

    Mashhadiabbas, Fatemeh; Neamatzadeh, Hossein; Nasiri, Rezvan; Foroughi, Elnaz; Farahnak, Soudabeh; Piroozmand, Parisa; Mazaheri, Mahta; Zare-Shehneh, Masoud

    2018-01-01

    There has been increasing interest in the study of the association between Vitamin D receptor (VDR) gene polymorphisms and risk of chronic periodontitis. However, the results remain inconclusive. To better understand the roles of VDR polymorphisms (BsmI, TaqI, FokI, and ApaI) in chronic periodontitis susceptibility, we conducted this systematic review and meta-analysis. The PubMed, Google Scholar, and Web of Science database were systemically searched to determine all the eligible studies about VDR polymorphisms and risk of chronic periodontitis up to April 2017. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between VDR polymorphisms and chronic periodontitis risk. All the statistical analyses were performed by Comprehensive Meta-Analysis. All P values were two-tailed with a significant level at 0.05. Finally, a total of 38 case-control studies in 19 publications were identified which met our inclusion criteria. There are ten studies with 866 chronic periodontitis cases and 786 controls for BsmI, 16 studies with 1570 chronic periodontitis cases and 1676 controls for TaqI, five studies with 374 chronic periodontitis cases and 382 controls for FokI, and seven studies with 632 chronic periodontitis cases and 604 controls for ApaI. Overall, no significant association was observed between VDR gene BsmI, TaqI, FokI, and ApaI polymorphisms and risk of chronic periodontitis in any genetic model. Subgroup analysis stratified by ethnicity suggested a significant association between BsmI polymorphism and chronic periodontitis risk in the Caucasian subgroup under allele model (A vs. G: OR = 1.747, 95% CI = 1.099-2.778, P = 0.018). Further, no significant associations were observed when stratified by Hardy-Weinberg equilibrium status for BsmI, TaqI, and ApaI. Our results suggest that BsmI, TaqI, FokI, and ApaI polymorphisms in the VDR gene might not be associated with risk of chronic periodontitis in overall population.

  7. Genetic association of telomere length with hepatocellular carcinoma risk: A Mendelian randomization analysis.

    Science.gov (United States)

    Cheng, Yue; Yu, Chengxiao; Huang, Mingtao; Du, Fangzhi; Song, Ci; Ma, Zijian; Zhai, Xiangjun; Yang, Yuan; Liu, Jibin; Bei, Jin-Xin; Jia, Weihua; Jin, Guangfu; Li, Shengping; Zhou, Weiping; Liu, Jianjun; Dai, Juncheng; Hu, Zhibin

    2017-10-01

    Observational studies show an association between telomere length and Hepatocellular carcinoma (HCC) risk, but the relationship is controversial. Particularly, it remains unclear whether the association is due to confounding or biases inherent in conventional epidemiological studies. Here, we applied Mendelian randomization approach to evaluate whether telomere length is causally associated with HCC risk. Individual-level data were from HBV-related HCC Genome-wide association studies (1,538 HBV positive HCC patients and 1,465 HBV positive controls). Genetic risk score, as proxy for actual measured telomere length, derived from nine telomere length-associated genetic variants was used to evaluate the effect of telomere length on HCC risk. We observed a significant risk signal between genetically increased telomere length and HBV-related HCC risk (OR=2.09, 95% CI 1.32-3.31, P=0.002). Furthermore, a U-shaped curve was fitted by the restricted cubic spline curve, which indicated that either short or long telomere length would increase HCC risk (P=0.0022 for non-linearity test). Subgroup analysis did not reveal significant heterogeneity between different age, gender, smoking status and drinking status groups. Our results indicated that a genetic background that favors longer or shorter telomere length may increase HBV-related HCC risk-a U-shaped association. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Phenotypic and Genomic Analysis of Hypervirulent Human-associated Bordetella bronchiseptica

    Directory of Open Access Journals (Sweden)

    Ahuja Umesh

    2012-08-01

    Full Text Available Abstract Background B. bronchiseptica infections are usually associated with wild or domesticated animals, but infrequently with humans. A recent phylogenetic analysis distinguished two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Complex IV isolates appear to have a bias for infecting humans; however, little is known regarding their epidemiology, virulence properties, or comparative genomics. Results Here we report a characterization of the virulence of human-associated complex IV B. bronchiseptica strains. In in vitro cytotoxicity assays, complex IV strains showed increased cytotoxicity in comparison to a panel of complex I strains. Some complex IV isolates were remarkably cytotoxic, resulting in LDH release levels in A549 cells that were 10- to 20-fold greater than complex I strains. In vivo, a subset of complex IV strains was found to be hypervirulent, with an increased ability to cause lethal pulmonary infections in mice. Hypercytotoxicity in vitro and hypervirulence in vivo were both dependent on the activity of the bsc T3SS and the BteA effector. To clarify differences between lineages, representative complex IV isolates were sequenced and their genomes were compared to complex I isolates. Although our analysis showed there were no genomic sequences that can be considered unique to complex IV strains, there were several loci that were predominantly found in complex IV isolates. Conclusion Our observations reveal a T3SS-dependent hypervirulence phenotype in human-associated complex IV isolates, highlighting the need for further studies on the epidemiology and evolutionary dynamics of this B. bronchiseptica lineage.

  9. An actor-partner interdependence analysis of associations between affect and parenting behavior among couples.

    Science.gov (United States)

    Murdock, Kyle W; Lovejoy, M Christine; Oddi, Kate B

    2014-03-01

    Prior studies evaluating associations between parental affect and parenting behavior have typically focused on either mothers or fathers despite evidence suggesting that affect and parenting behavior may be interdependent among couples. This study addressed this gap in the literature by evaluating associations between self-reported affect and parenting behavior using an actor-partner interdependence analysis among a sample of 53 mother-father dyads of 3- to 5-year-old children. Results suggested that mothers' and fathers' negative affect, as well as mothers' and fathers' positive affect, were positively associated. Both mothers' and fathers' negative affect were negatively associated with fathers' positive affect. Mothers' and fathers' harsh/negative parenting behavior, and supportive/engaged parenting behavior, were positively associated. Furthermore, mothers' negative affect was positively associated with mothers' and fathers' harsh/negative parenting behavior while mothers' positive affect was negatively associated with mothers' harsh/negative behavior and positively associated with mothers' supportive/engaged behavior. Fathers' negative affect was positively associated with fathers' supportive/engaged parenting behavior, while fathers' positive affect was positively associated with mothers' and fathers' supportive/engaged behavior. Results highlight the importance of conceptualizing and measuring characteristics of both mothers and fathers, if applicable, when researching the dynamics of interpersonal relationships within families. © 2014 FPI, Inc.

  10. Hospitalization for partial nephrectomy was not associated with intrathecal opioid analgesia: Retrospective analysis.

    Science.gov (United States)

    Weingarten, Toby N; Del Mundo, Serena B; Yeoh, Tze Yeng; Scavonetto, Federica; Leibovich, Bradley C; Sprung, Juraj

    2014-10-01

    The aim of this retrospective study is to test the hypothesis that the use of spinal analgesia shortens the length of hospital stay after partial nephrectomy. We reviewed all patients undergoing partial nephrectomy for malignancy through flank incision between January 1, 2008, and June 30, 2011. We excluded patients who underwent tumor thrombectomy, used sustained-release opioids, or had general anesthesia supplemented by epidural analgesia. Patients were grouped into "spinal" (intrathecal opioid injection for postoperative analgesia) versus "general anesthetic" group, and "early" discharge group (within 3 postoperative days) versus "late" group. Association between demographics, patient physical status, anesthetic techniques, and surgical complexity and hospital stay were analyzed using multivariable logistic regression analysis. Of 380 patients, 158 (41.6%) were discharged "early" and 151 (39.7%) were "spinal" cases. Both spinal and early discharge groups had better postoperative pain control and used less postoperative systemic opioids. Spinal analgesia was associated with early hospital discharge, odds ratio 1.52, (95% confidence interval 1.00-2.30), P = 0.05, but in adjusted analysis was no longer associated with early discharge, 1.16 (0.73-1.86), P = 0.52. Early discharge was associated with calendar year, with more recent years being associated with early discharge. Spinal analgesia combined with general anesthesia was associated with improved postoperative pain control during the 1(st) postoperative day, but not with shorter hospital stay following partial nephrectomy. Therefore, unaccounted practice changes that occurred during more recent times affected hospital stay.

  11. Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis.

    Science.gov (United States)

    Chopra, Vineet; Anand, Sarah; Hickner, Andy; Buist, Michael; Rogers, Mary Am; Saint, Sanjay; Flanders, Scott A

    2013-07-27

    Peripherally inserted central catheters (PICCs) are associated with an increased risk of venous thromboembolism. However, the size of this risk relative to that associated with other central venous catheters (CVCs) is unknown. We did a systematic review and meta-analysis to compare the risk of venous thromboembolism associated with PICCs versus that associated with other CVCs. We searched several databases, including Medline, Embase, Biosis, Cochrane Central Register of Controlled Trials, Conference Papers Index, and Scopus. Additional studies were identified through hand searches of bibliographies and internet searches, and we contacted study authors to obtain unpublished data. All human studies published in full text, abstract, or poster form were eligible for inclusion. All studies were of adult patients aged at least 18 years who underwent insertion of a PICC. Studies were assessed with the Newcastle-Ottawa risk of bias scale. In studies without a comparison group, the pooled frequency of venous thromboembolism was calculated for patients receiving PICCs. In studies comparing PICCs with other CVCs, summary odds ratios (ORs) were calculated with a random effects meta-analysis. Of the 533 citations identified, 64 studies (12 with a comparison group and 52 without) including 29 503 patients met the eligibility criteria. In the non-comparison studies, the weighted frequency of PICC-related deep vein thrombosis was highest in patients who were critically ill (13·91%, 95% CI 7·68-20·14) and those with cancer (6·67%, 4·69-8·64). Our meta-analysis of 11 studies comparing the risk of deep vein thrombosis related to PICCs with that related to CVCs showed that PICCs were associated with an increased risk of deep vein thrombosis (OR 2·55, 1·54-4·23, p<0·0001) but not pulmonary embolism (no events). With the baseline PICC-related deep vein thrombosis rate of 2·7% and pooled OR of 2·55, the number needed to harm relative to CVCs was 26 (95% CI 13-71). PICCs are

  12. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

    NARCIS (Netherlands)

    Demenais, Florence; Margaritte-Jeannin, Patricia; Barnes, Kathleen C; Cookson, William O C; Altmüller, Janine; Ang, Wei; Barr, R Graham; Beaty, Terri H; Becker, Allan B; Beilby, John; Bisgaard, Hans; Bjornsdottir, Unnur Steina; Bleecker, Eugene; Bønnelykke, Klaus; Boomsma, Dorret I; Bouzigon, Emmanuelle; Brightling, Christopher E; Brossard, Myriam; Brusselle, Guy G; Burchard, Esteban; Burkart, Kristin M; Bush, Andrew; Chan-Yeung, Moira; Chung, Kian Fan; Couto Alves, Alexessander; Curtin, John A; Custovic, Adnan; Daley, Denise; de Jongste, Johan C; Del-Rio-Navarro, Blanca E; Donohue, Kathleen M; Duijts, Liesbeth; Eng, Celeste; Eriksson, Johan G; Farrall, Martin; Fedorova, Yuliya; Feenstra, Bjarke; Ferreira, Manuel A; Freidin, Maxim B; Gajdos, Zofia; Gauderman, Jim; Gehring, Ulrike; Geller, Frank; Genuneit, Jon; Gharib, Sina A; Gilliland, Frank; Granell, Raquel; Graves, Penelope E; Gudbjartsson, Daniel F; Haahtela, Tari; Heckbert, Susan R; Heederik, Dick; Heinrich, Joachim; Heliövaara, Markku; Henderson, John; Himes, Blanca E; Hirose, Hiroshi; Hirschhorn, Joel N; Hofman, Albert; Holt, Patrick; Hottenga, Jouke; Hudson, Thomas J; Hui, Jennie; Imboden, Medea; Ivanov, Vladimir; Jaddoe, Vincent W V; James, Alan; Janson, Christer; Jarvelin, Marjo-Riitta; Jarvis, Deborah; Jones, Graham; Jonsdottir, Ingileif; Jousilahti, Pekka; Kabesch, Michael; Kähönen, Mika; Kantor, David B; Karunas, Alexandra S; Khusnutdinova, Elza; Koppelman, Gerard H; Kozyrskyj, Anita L; Kreiner, Eskil; Kubo, Michiaki; Kumar, Rajesh; Kumar, Ashish; Kuokkanen, Mikko; Lahousse, Lies; Laitinen, Tarja; Laprise, Catherine; Lathrop, Mark; Lau, Susanne; Lee, Young-Ae; Lehtimäki, Terho; Letort, Sébastien; Levin, Albert M; Li, Guo; Liang, Liming; Loehr, Laura R; London, Stephanie J; Loth, Daan W; Manichaikul, Ani; Marenholz, Ingo; Martinez, Fernando J; Matheson, Melanie C; Mathias, Rasika A; Matsumoto, Kenji; Mbarek, Hamdi; McArdle, Wendy L; Melbye, Mads; Melén, Erik; Meyers, Deborah; Michel, Sven; Mohamdi, Hamida; Musk, Arthur W; Myers, Rachel A; Nieuwenhuis, Maartje A E; Noguchi, Emiko; O'Connor, George T; Ogorodova, Ludmila M; Palmer, Cameron D; Palotie, Aarno; Park, Julie E; Pennell, Craig E; Pershagen, Göran; Polonikov, Alexey; Postma, Dirkje S; Probst-Hensch, Nicole; Puzyrev, Valery P; Raby, Benjamin A; Raitakari, Olli T; Ramasamy, Adaikalavan; Rich, Stephen S; Robertson, Colin F; Romieu, Isabelle; Salam, Muhammad T; Salomaa, Veikko; Schlünssen, Vivi; Scott, Robert; Selivanova, Polina A; Sigsgaard, Torben; Simpson, Angela; Siroux, Valérie; Smith, Lewis J; Solodilova, Maria; Standl, Marie; Stefansson, Kari; Strachan, David P; Stricker, Bruno H; Takahashi, Atsushi; Thompson, Philip J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tiesler, Carla M T; Torgerson, Dara G; Tsunoda, Tatsuhiko; Uitterlinden, André G; van der Valk, Ralf J P; Vaysse, Amaury; Vedantam, Sailaja; von Berg, Andrea; von Mutius, Erika; Vonk, Judith M; Waage, Johannes; Wareham, Nick J; Weiss, Scott T; White, Wendy B; Wickman, Magnus; Widén, Elisabeth; Willemsen, Gonneke; Williams, L Keoki; Wouters, Inge M; Yang, James J; Zhao, Jing Hua; Moffatt, Miriam F; Ober, Carole; Nicolae, Dan L

    We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma

  13. Association between smoking and risk of primary biliary cirrhosis: a meta-analysis

    Directory of Open Access Journals (Sweden)

    FAN Junyu

    2015-10-01

    Full Text Available ObjectiveTo systematically evaluate the association between smoking and the risk of primary biliary cirrhosis (PBC from the perspective of evidence-based medicine. MethodsA literature search was performed in PubMed, EMBASE, CBM, CNKI, Wanfang Data, and VIP database to collect the case-control studies on the association between smoking and the risk of PBC published in the last two decades. Chinese search words were “吸烟”, “香烟”, “原发性胆汁性肝硬化”, “危险因素”, “队列研究”, and “病例对照研究”, and English search words were “smoking”, “cigarette”, “tobacco”, “risk factors”, “primary biliary cirrhosis”, “cohort studies”, and “case-control studies”. And then a meta-analysis was performed using Review Manager 5.2. The pooled odds ratio (OR and 95% confidence interval (CI were calculated, and the publication bias was analyzed by funnel plots. ResultsA total of 7 case-control studies involving 5459 subjects (2652 patients with PBC vs 2807 controls were included in the meta-analysis. The analysis results showed that smokers had a significantly higher risk of PBC compared with non-smokers (OR=1.49, 95% CI: 1.11-2.00, P=0.009. The geographical subgroup analysis results showed that there was a significant difference in the risk of PBC between non-smokers and smokers in North America (OR=1.57, 95% CI: 1.20-2.04, P=0.0008. However, there was no significant difference in the risk of PBC between non-smokers and smokers in Europe (OR=1.41, 95% CI: 0.73-2.73, P=0.31. ConclusionSmoking can increase the risk of PBC. However, it needs to be confirmed in high-quality prospective studies with larger samples because of the heterogeneity of current included studies.

  14. Association between Dietary Patterns and the Indicators of Obesity among Chinese: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Long Shu

    2015-09-01

    Full Text Available No previous study has investigated dietary pattern in association with obesity risk in a middle-aged Chinese population. The purpose of this study was to evaluate the associations between dietary patterns and the risk of obesity in the city of Hangzhou, the capital of Zhejiang Province, east China. In this cross-sectional study of 2560 subjects aged 45–60 years, dietary intakes were evaluated using a semi-quantitative food frequency questionnaire (FFQ. All anthropometric measurements were obtained using standardized procedures. The partial correlation analysis was performed to assess the associations between dietary patterns and body mass index (BMI, waist circumference (WC, and waist to hip ratio (WHR. Multivariate logistic regression analysis was used to examine the associations between dietary patterns and obesity, with adjustment for potential confounders. Four major dietary patterns were extracted by means of factor analysis: animal food, traditional Chinese, western fast-food, and high-salt patterns. The animal food pattern was positively associated with BMI (r = 0.082, 0.144, respectively, p < 0.05 and WC (r = 0.102, 0.132, respectively, p < 0.01, and the traditional Chinese pattern was inversely associated with BMI (r = −0.047, −0.116, respectively, p < 0.05 and WC (r = −0.067, −0.113, respectively, p < 0.05 in both genders. After controlling for potential confounders, subjects in the highest quartile of animal food pattern scores had a greater odds ratio for abdominal obesity (odds ratio (OR = 1.67; 95% confidence interval (CI: 1.188–2.340; p < 0.01, in comparison to those from the lowest quartile. Compared with the lowest quartile of the traditional Chinese pattern, the highest quartile had a lower odds ratio for abdominal obesity (OR = 0.63; 95% CI: 0.441–0.901, p < 0.05. Conclusions: Our findings indicated that the animal food pattern was associated with a higher risk of abdominal obesity, while the traditional Chinese

  15. Association between dietary patterns and cognitive function among 70-year-old Japanese elderly: a cross-sectional analysis of the SONIC study.

    Science.gov (United States)

    Okubo, Hitomi; Inagaki, Hiroki; Gondo, Yasuyuki; Kamide, Kei; Ikebe, Kazunori; Masui, Yukie; Arai, Yasumichi; Ishizaki, Tatsuro; Sasaki, Satoshi; Nakagawa, Takeshi; Kabayama, Mai; Sugimoto, Ken; Rakugi, Hiromi; Maeda, Yoshinobu

    2017-09-11

    An increasing number of studies in Western countries have shown that healthy dietary patterns may have a protective effect against cognitive decline and dementia. However, information on this relationship among non-Western populations with different cultural settings is extremely limited. We aim to examine the relationship between dietary patterns and cognitive function among older Japanese people. This cross-sectional study included 635 community-dwelling people aged 69-71 years who participated in the prospective cohort study titled Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC). Diet was assessed over a one-month period with a validated, brief-type, self-administered diet history questionnaire. Dietary patterns from thirty-three predefined food groups [energy-adjusted food (g/d)] were extracted by factor analysis. Cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Multivariate regression analysis was performed to examine the relationship between dietary patterns and cognitive function. Three dietary patterns were identified: the 'Plant foods and fish', 'Rice and miso soup', and 'Animal food' patterns. The 'Plant foods and fish' pattern, characterized by high intakes of green and other vegetables, soy products, seaweeds, mushrooms, potatoes, fruit, fish, and green tea, was significantly associated with a higher MoCA-J score [MoCA-J score per one-quartile increase in dietary pattern: β = 0.56 (95% CI: 0.33, 0.79), P for trend cognitive function. To confirm the possibility of reverse causation we also conducted a sensitivity analysis excluding 186 subjects who reported substantial changes in their diet for any reason, but the results did not change materially. This preliminary cross-sectional study suggests that a diet with high intakes of vegetables, soy products, fruit, and fish may have a beneficial effect on cognitive function in older Japanese people. Further

  16. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

    NARCIS (Netherlands)

    C.M. Lindgren (Cecilia); I.M. Heid (Iris); J.C. Randall (Joshua); C. Lamina (Claudia); V. Steinthorsdottir (Valgerdur); L. Qi (Lu); E.K. Speliotes (Elizabeth); G. Thorleifsson (Gudmar); C.J. Willer (Cristen); B.M. Herrera (Blanca); A.U. Jackson (Anne); N. Lim (Noha); P. Scheet (Paul); N. Soranzo (Nicole); N. Amin (Najaf); Y.S. Aulchenko (Yurii); J.C. Chambers (John); A. Drong (Alexander); J. Luan; H.N. Lyon (Helen); F. Rivadeneira Ramirez (Fernando); S. Sanna (Serena); N.J. Timpson (Nicholas); M.C. Zillikens (Carola); H.Z. Jing; P. Almgren (Peter); S. Bandinelli (Stefania); A.J. Bennett (Amanda); R.N. Bergman (Richard); L.L. Bonnycastle (Lori); S. Bumpstead (Suzannah); S.J. Chanock (Stephen); L. Cherkas (Lynn); P.S. Chines (Peter); L. Coin (Lachlan); C. Cooper (Charles); G. Crawford (Gabe); A. Doering (Angela); A. Dominiczak (Anna); A.S.F. Doney (Alex); S. Ebrahim (Shanil); P. Elliott (Paul); M.R. Erdos (Michael); K. Estrada Gil (Karol); L. Ferrucci (Luigi); G. Fischer (Guido); N.G. Forouhi (Nita); C. Gieger (Christian); H. Grallert (Harald); C.J. Groves (Christopher); S.M. Grundy (Scott); C. Guiducci (Candace); D. Hadley (David); A. Hamsten (Anders); A.S. Havulinna (Aki); A. Hofman (Albert); R. Holle (Rolf); J.W. Holloway (John); T. Illig (Thomas); B. Isomaa (Bo); L.C. Jacobs (Leonie); K. Jameson (Karen); P. Jousilahti (Pekka); F. Karpe (Fredrik); J. Kuusisto (Johanna); J. Laitinen (Jaana); G.M. Lathrop (Mark); D.A. Lawlor (Debbie); M. Mangino (Massimo); W.L. McArdle (Wendy); T. Meitinger (Thomas); M.A. Morken (Mario); A.P. Morris (Andrew); P. Munroe (Patricia); N. Narisu (Narisu); A. Nordström (Anna); B.A. Oostra (Ben); C.N.A. Palmer (Colin); F. Payne (Felicity); J. Peden (John); I. Prokopenko (Inga); F. Renström (Frida); A. Ruokonen (Aimo); V. Salomaa (Veikko); M.S. Sandhu (Manjinder); L.J. Scott (Laura); A. Scuteri (Angelo); K. Silander (Kaisa); K. Song (Kijoung); X. Yuan (Xin); H.M. Stringham (Heather); A.J. Swift (Amy); T. Tuomi (Tiinamaija); M. Uda (Manuela); P. Vollenweider (Peter); G. Waeber (Gérard); C. Wallace (Chris); G.B. Walters (Bragi); M.N. Weedon (Michael); J.C.M. Witteman (Jacqueline); C. Zhang (Cuilin); M. Caulfield (Mark); F.S. Collins (Francis); G.D. Smith; I.N.M. Day (Ian); P.W. Franks (Paul); A.T. Hattersley (Andrew); F.B. Hu (Frank); M.-R. Jarvelin (Marjo-Riitta); A. Kong (Augustine); J.S. Kooner (Jaspal); M. Laakso (Markku); E. Lakatta (Edward); V. Mooser (Vincent); L. Peltonen (Leena Johanna); N.J. Samani (Nilesh); T.D. Spector (Timothy); D.P. Strachan (David); T. Tanaka (Toshiko); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); N.J. Wareham (Nick); H. Watkins (Hugh); D. Waterworth (Dawn); M. Boehnke (Michael); P. Deloukas (Panagiotis); L. Groop (Leif); D.J. Hunter (David); U. Thorsteinsdottir (Unnur); D. Schlessinger (David); H.E. Wichmann (Erich); T.M. Frayling (Timothy); G.R. Abecasis (Gonçalo); J.N. Hirschhorn (Joel); R.J.F. Loos (Ruth); J-A. Zwart (John-Anker); K.L. Mohlke (Karen); I.E. Barroso (Inês); M.I. McCarthy (Mark)

    2009-01-01

    textabstractTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the

  17. Association between hypoxia and perinatal arterial ischemic stroke: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Lili Luo

    Full Text Available Perinatal arterial ischemic stroke (AIS occurs in an estimated 17 to 93 per 100000 live births, yet the etiology is poorly understood. Although investigators have implicated hypoxia as a potential cause of AIS, the role of hypoxia in AIS remains controversial. The aim of this study was to estimate the association between perinatal hypoxia factors and perinatal arterial ischemic stroke through a meta-analysis of published observational studies.A systematic search of electronically available studies published through July 2013 was conducted. Publication bias and heterogeneity across studies were evaluated and summary odds ratios (ORs and 95% confidence intervals (CIs were calculated with fixed-effects or random-effects models.A total of 8 studies describing the association between perinatal hypoxia factors and neonatal arterial ischemic stroke (AIS met inclusion criteria, and 550 newborns with AIS were enrolled. The associations were found for AIS: preeclampsia (OR 2.14; 95% CI, 1.25 to 3.66, ventouse delivery (OR 2.23; 95% CI, 1.26 to 3.97, fetal heart rate abnormalities (OR 6.30; 95% CI, 3.84 to 10.34, reduced fetal movement (OR 5.35; 95% CI, 2.17 to 13.23, meconium-stained liquor (OR 3.05; 95% CI, 2.02 to 4.60, low Apgar score (OR 5.77; 95% CI, 1.66 to 20.04 and resuscitation at birth (OR 4.59; 95% CI, 3.23 to 6.52. Our data did not show any significant change of the mean risk estimate for oxytocin induction (OR 1.33; 95% CI, 0.84 to 2.11 and low arterial umbilical cord ph (OR 4.63; 95% CI 2.14 to 9.98.There is a significant association between perinatal hypoxia factors and AIS. The result indicates that perinatal hypoxia maybe one of causes of AIS. Large scale prospective clinical studies are still warranted.

  18. Analysis of a Shock-Associated Noise Prediction Model Using Measured Jet Far-Field Noise Data

    Science.gov (United States)

    Dahl, Milo D.; Sharpe, Jacob A.

    2014-01-01

    A code for predicting supersonic jet broadband shock-associated noise was assessed using a database containing noise measurements of a jet issuing from a convergent nozzle. The jet was operated at 24 conditions covering six fully expanded Mach numbers with four total temperature ratios. To enable comparisons of the predicted shock-associated noise component spectra with data, the measured total jet noise spectra were separated into mixing noise and shock-associated noise component spectra. Comparisons between predicted and measured shock-associated noise component spectra were used to identify deficiencies in the prediction model. Proposed revisions to the model, based on a study of the overall sound pressure levels for the shock-associated noise component of the measured data, a sensitivity analysis of the model parameters with emphasis on the definition of the convection velocity parameter, and a least-squares fit of the predicted to the measured shock-associated noise component spectra, resulted in a new definition for the source strength spectrum in the model. An error analysis showed that the average error in the predicted spectra was reduced by as much as 3.5 dB for the revised model relative to the average error for the original model.

  19. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

    NARCIS (Netherlands)

    Nalls, Mike A.; Pankratz, Nathan; Lill, Christina M.; Do, Chuong B.; Hernandez, Dena G.; Saad, Mohamad; DeStefano, Anita L.; Kara, Eleanna; Bras, Jose; Sharma, Manu; Schulte, Claudia; Keller, Margaux F.; Arepalli, Sampath; Letson, Christopher; Edsall, Connor; Stefansson, Hreinn; Liu, Xinmin; Pliner, Hannah; Lee, Joseph H.; Cheng, Rong; Ikram, M. Arfan; Ioannidis, John P. A.; Hadjigeorgiou, Georgios M.; Bis, Joshua C.; Martinez, Maria; Perlmutter, Joel S.; Goate, Alison; Marder, Karen; Fiske, Brian; Sutherland, Margaret; Xiromerisiou, Georgia; Myers, Richard H.; Clark, Lorraine N.; Stefansson, Kari; Hardy, John A.; Heutink, Peter; Chen, Honglei; Wood, Nicholas W.; Houlden, Henry; Payami, Haydeh; Brice, Alexis; Scott, William K.; Gasser, Thomas; Bertram, Lars; Eriksson, Nicholas; Foroud, Tatiana; Singleton, Andrew B.; Plagnol, Vincent; Sheerin, Una-Marie; Simón-Sánchez, Javier; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M. A.; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, J. Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Dong, Jing; Gardner, Michelle; Gibbs, J. Raphael; Gray, Emma; Guerreiro, Rita; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Wurster, Isabel; Mätzler, Walter; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jónsson, Pálmi V.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R.; Morrison, Karen E.; Mudanohwo, Ese; O'Sullivan, Sean S.; Pearson, Justin; Pétursson, Hjörvar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C. A.; Stefánsson, Hreinn; Bettella, Francesco; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Stefánsson, Kári; Hardy, John; Factor, S.; Higgins, D.; Evans, S.; Shill, H.; Stacy, M.; Danielson, J.; Marlor, L.; Williamson, K.; Jankovic, J.; Hunter, C.; Simon, D.; Ryan, P.; Scollins, L.; Saunders-Pullman, R.; Boyar, K.; Costan-Toth, C.; Ohmann, E.; Sudarsky, L.; Joubert, C.; Friedman, J.; Chou, K.; Fernandez, H.; Lannon, M.; Galvez-Jimenez, N.; Podichetty, A.; Thompson, K.; Lewitt, P.; Deangelis, M.; O'Brien, C.; Seeberger, L.; Dingmann, C.; Judd, D.; Marder, K.; Fraser, J.; Harris, J.; Bertoni, J.; Peterson, C.; Rezak, M.; Medalle, G.; Chouinard, S.; Panisset, M.; Hall, J.; Poiffaut, H.; Calabrese, V.; Roberge, P.; Wojcieszek, J.; Belden, J.; Jennings, D.; Marek, K.; Mendick, S.; Reich, S.; Dunlop, B.; Jog, M.; Horn, C.; Uitti, R.; Turk, M.; Ajax, T.; Mannetter, J.; Sethi, K.; Carpenter, J.; Dill, B.; Hatch, L.; Ligon, K.; Narayan, S.; Blindauer, K.; Abou-Samra, K.; Petit, J.; Elmer, L.; Aiken, E.; Davis, K.; Schell, C.; Wilson, S.; Velickovic, M.; Koller, W.; Phipps, S.; Feigin, A.; Gordon, M.; Hamann, J.; Licari, E.; Marotta-Kollarus, M.; Shannon, B.; Winnick, R.; Simuni, T.; Videnovic, A.; Kaczmarek, A.; Williams, K.; Wolff, M.; Rao, J.; Cook, M.; Fernandez, M.; Kostyk, S.; Hubble, J.; Campbell, A.; Reider, C.; Seward, A.; Camicioli, R.; Carter, J.; Nutt, J.; Andrews, P.; Morehouse, S.; Stone, C.; Mendis, T.; Grimes, D.; Alcorn-Costa, C.; Gray, P.; Haas, K.; Vendette, J.; Sutton, J.; Hutchinson, B.; Young, J.; Rajput, A.; Klassen, L.; Shirley, T.; Manyam, B.; Simpson, P.; Whetteckey, J.; Wulbrecht, B.; Truong, D.; Pathak, M.; Frei, K.; Luong, N.; Tra, T.; Tran, A.; Vo, J.; Lang, A.; Kleiner- Fisman, G.; Nieves, A.; Johnston, L.; So, J.; Podskalny, G.; Giffin, L.; Atchison, P.; Allen, C.; Martin, W.; Wieler, M.; Suchowersky, O.; Furtado, S.; Klimek, M.; Hermanowicz, N.; Niswonger, S.; Shults, C.; Fontaine, D.; Aminoff, M.; Christine, C.; Diminno, M.; Hevezi, J.; Dalvi, A.; Kang, U.; Richman, J.; Uy, S.; Sahay, A.; Gartner, M.; Schwieterman, D.; Hall, D.; Leehey, M.; Culver, S.; Derian, T.; Demarcaida, T.; Thurlow, S.; Rodnitzky, R.; Dobson, J.; Lyons, K.; Pahwa, R.; Gales, T.; Thomas, S.; Shulman, L.; Weiner, W.; Dustin, K.; Singer, C.; Zelaya, L.; Tuite, P.; Hagen, V.; Rolandelli, S.; Schacherer, R.; Kosowicz, J.; Gordon, P.; Werner, J.; Serrano, C.; Roque, S.; Kurlan, R.; Berry, D.; Gardiner, I.; Hauser, R.; Sanchez-Ramos, J.; Zesiewicz, T.; Delgado, H.; Price, K.; Rodriguez, P.; Wolfrath, S.; Pfeiffer, R.; Davis, L.; Pfeiffer, B.; Dewey, R.; Hayward, B.; Johnson, A.; Meacham, M.; Estes, B.; Walker, F.; Hunt, V.; O'Neill, C.; Racette, B.; Swisher, L.; Dijamco, Cheri; Conley, Emily Drabant; Dorfman, Elizabeth; Tung, Joyce Y.; Hinds, David A.; Mountain, Joanna L.; Wojcicki, Anne; Lew, M.; Klein, C.; Golbe, L.; Growdon, J.; Wooten, G. F.; Watts, R.; Guttman, M.; Goldwurm, S.; Saint-Hilaire, M. H.; Baker, K.; Litvan, I.; Nicholson, G.; Nance, M.; Drasby, E.; Isaacson, S.; Burn, D.; Pramstaller, P.; Al-hinti, J.; Moller, A.; Sherman, S.; Roxburgh, R.; Slevin, J.; Perlmutter, J.; Mark, M. H.; Huggins, N.; Pezzoli, G.; Massood, T.; Itin, I.; Corbett, A.; Chinnery, P.; Ostergaard, K.; Snow, B.; Cambi, F.; Kay, D.; Samii, A.; Agarwal, P.; Roberts, J. W.; Higgins, D. S.; Molho, Eric; Rosen, Ami; Montimurro, J.; Martinez, E.; Griffith, A.; Kusel, V.; Yearout, D.; Zabetian, C.; Clark, L. N.; Liu, X.; Lee, J. H.; Taub, R. Cheng; Louis, E. D.; Cote, L. J.; Waters, C.; Ford, B.; Fahn, S.; Vance, Jeffery M.; Beecham, Gary W.; Martin, Eden R.; Nuytemans, Karen; Pericak-Vance, Margaret A.; Haines, Jonathan L.; DeStefano, Anita; Seshadri, Sudha; Choi, Seung Hoan; Frank, Samuel; Psaty, Bruce M.; Rice, Kenneth; Longstreth, W. T.; Ton, Thanh G. N.; Jain, Samay; van Duijn, Cornelia M.; Verlinden, Vincent J.; Koudstaal, Peter J.; Singleton, Andrew; Cookson, Mark; Hernandez, Dena; Nalls, Michael; Zonderman, Alan; Ferrucci, Luigi; Johnson, Robert; Longo, Dan; O'Brien, Richard; Traynor, Bryan; Troncoso, Juan; van der Brug, Marcel; Zielke, Ronald; Weale, Michael; Ramasamy, Adaikalavan; Dardiotis, Efthimios; Tsimourtou, Vana; Spanaki, Cleanthe; Plaitakis, Andreas; Bozi, Maria; Stefanis, Leonidas; Vassilatis, Dimitris; Koutsis, Georgios; Panas, Marios; Lunnon, Katie; Lupton, Michelle; Powell, John; Parkkinen, Laura; Ansorge, Olaf

    2014-01-01

    We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were

  20. Lack of association between the Serotonin Transporter Promoter Polymorphism (5-HTTLPR and Panic Disorder: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Manfro Gisele G

    2007-08-01

    Full Text Available Abstract Background The aim of this study is to assess the association between the Serotonin Transporter Promoter Polymorphism (5-HTTLPR and Panic Disorder (PD. Methods This is a systematic review and meta-analysis of case-control studies with unrelated individuals of any ethnic origin examining the role of the 5-HTTLPR in PD according to standard diagnostic criteria (DSM or ICD. Articles published in any language between January 1996 and April 2007 were eligible. The electronic databases searched included PubMed, PsychInfo, Lilacs and ISI. Two separate analyses were performed: an analysis by alleles and a stratified analysis separating studies by the quality of control groups. Asymptotic DerSimonian and Laird's Q test were used to assess heterogeneity. Results of individual studies were combined using the fixed effect model with respective 95% confidence intervals. Results Nineteen potential articles were identified, and 10 studies were included in this meta-analysis. No statistically significant association between 5-HTTLPR and PD was found, OR = 0.91 (CI95% 0.80 to 1.03, p = 0.14. Three sub-analyses divided by ethnicity, control group quality and Agoraphobia comorbidity also failed to find any significant association. No evidence of heterogeneity was found between studies in the analyses. Conclusion Results from this systematic review do not provide evidence to support an association between 5-HTTLPR and PD. However, more studies are needed in different ethnic populations in order to evaluate a possible minor effect.