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  1. STrengthening the REporting of Genetic Association Studies (STREGA – An Extension of the STROBE Statement

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    Julian Little

    2009-09-01

    Full Text Available Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

  2. Il corpo della strega

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    Georges Bertin

    2004-09-01

    Full Text Available Come già evidenziato a proposito di altre pratiche, il sabba, attività ludica profana, religiosa, conferiva a ciascuno la possibilità di giocare efficacemente con la dinamica di un mondo da cui emergeva una figura archetipica, la strega, principale attore di questa danza in tondo. Il sabba era, dunque, uno dei luoghi ove si cristallizzavano le figure del proibito, questo per il suo carattere sacro, per la violenza istituzionale che presiedeva alla formazione dei rapporti sociali, e conferiva anche, per le caratteristiche di protesta che rivela, un'immagine sempre esaltante della capacità delle società a resistere. Il problema della nostra epoca ove rifioriscono le streghe nelle più svariate forme è, forse, quello di riallacciarsi con la dimensione gruppale dei nostri svaghi, nelle loro differenti forme e, contemporaneamente, con perdita di energia, a quanto presiedeva ai sabba e alla loro risoluzione sacrificale. In contro-corrente ai modelli meccanici che assegnano dei limiti precisi e funzionali ai corpi asserviti ad un ideale di controllo, il corpo sabbatico con la sua enfasi sulle posizioni limite (ciò che si rimproverava d'altronde alle streghe, era veramente corpo mistico.

  3. Effect of interactions of polymorphisms in the Melanocortin-4 receptor gene with dietary factors on the risk of obesity and Type 2 diabetes: a systematic review.

    Science.gov (United States)

    Koochakpoor, G; Hosseini-Esfahani, F; Daneshpour, M S; Hosseini, S A; Mirmiran, P

    2016-08-01

    To perform a systematic review of the effect of interaction between Melanocortin-4 receptor (MC4R) single nucleotide polymorphisms and diet on the development of obesity and Type 2 diabetes. Environmental factors, such as nutrient intakes or feeding behaviours, can modulate the association of polymorphism in the MC4R gene with obesity and Type 2 diabetes mellitus. A systematic literature search was conducted in the PubMed, Scopus and Google Scholar databases, with a combination of the following keywords: Diet*, nutr*, melanocortin receptor, melanocortin 4 receptor and MC4R. To assess the quality of observational studies, we used a 12-item quality checklist, derived from the STREGA statement. A total of 14 articles were selected based on the inclusion and exclusion criteria. Consumption of highly salty foods and adherence to a Mediterranean dietary pattern can modulate the association between MC4R polymorphisms and the risk of obesity or Type 2 diabetes. Despite the highly contradictory results of intervention studies, after short-term lifestyle interventions, children with variant alleles of MC4R single nucleotide polymorphisms can lose more body weight, compared with non-carriers, although they may have difficulty in maintaining this weight loss in the long-term. To interpret the results of studies on adults, we need further studies. The interaction between MC4R genes with dietary factors plays a significant role in the development of obesity or Type 2 diabetes phenotypes. Early detection of MC4R risk alleles in individuals and modification of their diet based on these results could be an efficient strategy to prevent obesity or diabetes in these subgroups. © 2015 Diabetes UK.

  4. Methodological issues of genetic association studies.

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    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.

  5. Un altare per la madre: la lamentazione letteraria di Ferdinando Camon

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    Francesco Della Costa

    2016-05-01

    Full Text Available In una prospettiva antropologica, che considera la scrittura letteraria come una pratica culturale, questo articolo intende mostrare un’analogia funzionale tra rito e romanzo. In particolare, esso analizza la corrispondenza tra la lamentazione funebre, come è stata osservata negli anni Cinquanta dall’antropologo E. De Martino in alcune aree dell’Italia meridionale, e il romanzo di Ferdinando Camon, Un altare per la madre(Premio Strega del 1978. La scrittura è considerata qui come una reazione culturale alla “crisi del cordoglio” che la morte della madre attiva nel sé dello scrittore; nel contesto culturale di Camon, la letteratura assume lo stesso significato che, nel contesto folklorico meridionale studiato da De Martino, la lamentazione assumeva per le donne in lutto. Entrambe le pratiche, anche se molto diverse in sé, operano una “destorificazione” del tempo e una metaforizzazione della realtà: hanno il potere, così, di trasformare la tragedia individuale della morte in un dramma (col doppio significato di evento doloroso e rappresentazione universale, quindi di neturalizzarla e risolverla. In an anthropological perspective, which considers literature as a cultural practice, this article aims to show the functional analogy between ritual and novel. In particular, it analyzes the correspondences between the mourning lamentation ritual, as it has been observed in the 1950s by the anthropologist E. De Martino within some rural areas of Southern Italy, and F. Camon’s novel, Un altare per la madre (Premio Strega 1978. Writing is considered as a reaction to the «crisi del cordoglio» (the mourning crisis the death of his mother causes in the writer’s self; within Camon’s cultural context, literature assumes the same meaning which, in the southern folkloric context, lamentation assumed for mourning women. Both the practices, even though they are very different, operate a «destorificazione» (destorification of time and

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

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    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.

  7. “Pozzoromolo”, la tragica armonia della dissonanza

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    Teresa Ferri

    2010-07-01

    Full Text Available Pozzoromolo is the second novel by the promising young writer Luigi Romolo Carrino. The novel, which has been shortlisted for the Premio Strega, is analyzed in this essay by applying linguistic-symbolical parameters. It is shown that these, already in the ambivalence of the protagonist, underline how language, characters, style, and narrative underlie the novel’s structure. Starting with the title and the name of the first-person narrator, the novel’s most important themes are analyzed. From the function of parental figures and a series of obvious intertextual echoes, one cannot but conclude that the main character’s split personality, distorted by the nature of the writing, also finds expression in the novel’s idiolectal solutions. It is in these that one can perceive the writer’s stylistic acrobatics, the consistent fragmentation of the diaristic narrative, and the interesting linguistic blend, which is made up of irregular sentences, intertextual echoes of literary and popular sources, original formal results and lyrical representations.

  8. From Genome-Wide Association Study to Phenome-Wide Association Study: New Paradigms in Obesity Research.

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    Zhang, Y-P; Zhang, Y-Y; Duan, D D

    2016-01-01

    Obesity is a condition in which excess body fat has accumulated over an extent that increases the risk of many chronic diseases. The current clinical classification of obesity is based on measurement of body mass index (BMI), waist-hip ratio, and body fat percentage. However, these measurements do not account for the wide individual variations in fat distribution, degree of fatness or health risks, and genetic variants identified in the genome-wide association studies (GWAS). In this review, we will address this important issue with the introduction of phenome, phenomics, and phenome-wide association study (PheWAS). We will discuss the new paradigm shift from GWAS to PheWAS in obesity research. In the era of precision medicine, phenomics and PheWAS provide the required approaches to better definition and classification of obesity according to the association of obese phenome with their unique molecular makeup, lifestyle, and environmental impact. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Genome-wide association study of multiplex schizophrenia pedigrees

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    Levinson, Douglas F; Shi, Jianxin; Wang, Kai

    2012-01-01

    The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs).......The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs)....

  10. Association Study of Three Gene Polymorphisms Recently Identified by a Genome-Wide Association Study with Obesity-Related Phenotypes in Chinese Children.

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    Song, Qi-Ying; Song, Jie-Yun; Wang, Yang; Wang, Shuo; Yang, Yi-De; Meng, Xiang-Rui; Ma, Jun; Wang, Hai-Jun; Wang, Yan

    2017-01-01

    This study aimed to examine associations of three single-nucleotide polymorphisms (SNPs) with obesity-related phenotypes in Chinese children. These SNPs were identified by a recent genome-wide association (GWA) study among European children. Given that varied genetic backgrounds across different ethnicity may result in different association, it is necessary to study these associations in a different ethnic population. A total of 3,922 children, including 2,191 normal-weight, 873 overweight and 858 obese children, from three independent studies were included in the study. Logistic and linear regressions were performed, and meta-analyses were conducted to assess the associations between the SNPs and obesity-related phenotypes. The pooled odds ratios of the A-allele of rs564343 in PACS1 for obesity and severe obesity were 1.180 (p = 0.03) and 1.312 (p = 0.004), respectively. We also found that rs564343 was nominally associated with BMI, BMI standard deviation score (BMI-SDS), waist circumference, and waist-to-height ratio (p obesity in a non-European population. This SNP was also found to be associated with common obesity and various obesity-related phenotypes in Chinese children, which had not been reported in the original study. The results demonstrated the value of conducting genetic researches in populations with different ethnicity. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

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

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    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.

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

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    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.

  13. Genome-wide association study of serum selenium concentrations

    DEFF Research Database (Denmark)

    Gong, Jian; Hsu, Li; Harrison, Tabitha

    2013-01-01

    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

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

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    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.

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

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    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.

  16. Genome-wide association study identifies 74 loci associated with educational attainment

    DEFF Research Database (Denmark)

    Okbay, Aysu; P. Beauchamp, Jonathan; Alan Fontana, Mark

    2016-01-01

    -nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural......Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends...... development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals...

  17. Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy

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    Feenstra, Bjarke; Bager, Peter; Liu, Xueping

    2017-01-01

    BACKGROUND: Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. OBJECTIVE: To identify common genetic variants associate...... the molecular mechanisms underlying the genetic association involve general lymphoid hyper-reaction throughout the mucosa-associated lymphoid tissue system.......BACKGROUND: Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. OBJECTIVE: To identify common genetic variants associated...... with tonsillectomy. METHODS: We used tonsillectomy information from Danish health registers and carried out a genome-wide association study comprising 1464 patients and 12 019 controls of Northwestern European ancestry, with replication in an independent sample set of 1575 patients and 1367 controls. RESULTS...

  18. Genome-wide Association Study of Personality Traits in the Long Life Family Study

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    Harold T Bae

    2013-05-01

    Full Text Available Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we performed a genome-wide association study (GWAS on personality factors assessed by NEO-FFI in individuals enrolled in the Long Life Family Study (LLFS, a study of 583 families (N up to 4595 with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p<10-8 and replicated in an additional sample of 1279 LLFS subjects, although one (rs9650241 failed to replicate and the other two were not available in two independent replication cohorts, the Baltimore Longitudinal Study of Aging and the New England Centenarian Study. Based on 10,000,000 permutations, the empirical p-value of 2X10-7 was observed for the genome-wide significant SNPs. Seventeen SNPs that reached marginal statistical significance in the two previous GWASs (p-value < 10-4 and 10-5, were also marginally significantly associated in this study (p-value < 0.05, although none of the associations passed the Bonferroni correction. In addition, we tested age-by-SNP interactions and found some significant associations. Since scores of personality traits in LLFS subjects change in the oldest ages, and genetic factors outweigh environmental factors to achieve extreme ages, these age-by-SNP interactions could be a proxy for complex gene-gene interactions affecting personality traits and longevity.

  19. Considerations for Pharmacoepidemiological Studies of Drug-Cancer Associations

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    Pottegård, Anton; Friis, Søren; Stürmer, Til

    2018-01-01

    and future perspectives. Aspects of data sources include assessment of complete history of drug use and data on dose and duration of drug use, allowing estimates of cumulative exposure. Outcome data from formal cancer registries are preferable, but cancer data from other sources, for example, patient......In this MiniReview, we provide general considerations for the planning and conduct of pharmacoepidemiological studies of associations between drug use and cancer development. We address data sources, study design, assessment of drug exposure, ascertainment of cancer outcomes, confounder adjustment...... or pathology registries, medical records or claims are also suitable. The two principal designs for observational studies evaluating drug-cancer associations are the cohort and case-control designs. A key challenge in studies of drug-cancer associations is the exposure assessment due to the typically long...

  20. Genome-wide population-based association study of extremely overweight young adults--the GOYA study

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    Paternoster, Lavinia; Evans, David M; Nohr, Ellen Aagaard

    2011-01-01

    Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ∼1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight...

  1. Adiponectin Concentrations: A Genome-wide Association Study

    OpenAIRE

    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

    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 a...

  2. 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.

  3. 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.

  4. 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

  5. New progress of the study on uranium-gold association

    International Nuclear Information System (INIS)

    Feng Mingyue; Sun Zhifu

    1992-01-01

    Through the study on heavy minerals from the uraniferous granite-pegmatite it is found that nature gold is associated with uraninite, which provides the new information for the study on uranium-gold association and its metallogenesis

  6. New progress of the study on uranium-gold association

    Energy Technology Data Exchange (ETDEWEB)

    Mingyue, Feng; Zhifu, Sun [Beijing Research Inst. of Uranium Geology (China)

    1992-07-01

    Through the study on heavy minerals from the uraniferous granite-pegmatite it is found that nature gold is associated with uraninite, which provides the new information for the study on uranium-gold association and its metallogenesis.

  7. Genome-wide association study identifies 74 loci associated with educational attainment

    Science.gov (United States)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark A.; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Börge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bønnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans68, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldórsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kähönen, Mika; Kanoni, Stavroula; Keltigangas-Järvinen, Liisa; Kiemeney, Lambertus A.L.M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Maël P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C.M.; Loukola, Anu; Madden, Pamela A.; Mägi, Reedik; Mäki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E.R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Räikkönen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J.A.; Venturini, Cristina; Vinkhuyzen, Anna A.E.; Völker, Uwe; Völzke, Henry; Vonk, Judith M.; Vozzi, Diego; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jörgen; Gratten, Jacob; Groenen, Patrick J.F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppönen, Elina; Iacono, William G.; Jacobsson, Bo; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L.R.; Lehtimäki, Terho; Lehrer, Steven F.; Magnusson, Patrik K.E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W.J.H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sørensen, Thorkild I.A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, André G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tõnu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.

    2016-01-01

    Summary Educational attainment (EA) is strongly influenced by social and other environmental factors, but genetic factors are also estimated to account for at least 20% of the variation across individuals1. We report the results of a genome-wide association study (GWAS) for EA that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication in an independent sample of 111,349 individuals from the UK Biobank. We now identify 74 genome-wide significant loci associated with number of years of schooling completed. Single-nucleotide polymorphisms (SNPs) associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioral phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because EA is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric disease. PMID:27225129

  8. Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: The HyperGEN Study

    Directory of Open Access Journals (Sweden)

    Kraemer Rachel

    2009-05-01

    Full Text Available Abstract Background We conducted a genome-wide association study (GWAS and validation study for left ventricular (LV mass in the Family Blood Pressure Program – HyperGEN population. LV mass is a sensitive predictor of cardiovascular mortality and morbidity in all genders, races, and ages. Polymorphisms of candidate genes in diverse pathways have been associated with LV mass. However, subsequent studies have often failed to replicate these associations. Genome-wide association studies have unprecedented power to identify potential genes with modest effects on left LV mass. We describe here a GWAS for LV mass in Caucasians using the Affymetrix GeneChip Human Mapping 100 k Set. Cases (N = 101 and controls (N = 101 were selected from extreme tails of the LV mass index distribution from 906 individuals in the HyperGEN study. Eleven of 12 promising (Q Results Despite the relatively small sample, we identified 12 promising SNPs in the GWAS. Eleven SNPs were successfully genotyped in the validation study of 704 Caucasians and 1467 African Americans; 5 SNPs on chromosomes 5, 12, and 20 were significantly (P ≤ 0.05 associated with LV mass after correction for multiple testing. One SNP (rs756529 is intragenic within KCNB1, which is dephosphorylated by calcineurin, a previously reported candidate gene for LV hypertrophy within this population. Conclusion These findings suggest KCNB1 may be involved in the development of LV hypertrophy in humans.

  9. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    A. Okbay (Aysu); J.P. Beauchamp (Jonathan); Fontana, M.A. (Mark Alan); J.J. Lee (James J.); T.H. Pers (Tune); Rietveld, C.A. (Cornelius A.); P. Turley (Patrick); Chen, G.-B. (Guo-Bo); V. Emilsson (Valur); Meddens, S.F.W. (S. Fleur W.); Oskarsson, S. (Sven); Pickrell, J.K. (Joseph K.); Thom, K. (Kevin); Timshel, P. (Pascal); R. de Vlaming (Ronald); A. Abdellaoui (Abdel); T.S. Ahluwalia (Tarunveer Singh); J. Bacelis (Jonas); C. Baumbach (Clemens); Bjornsdottir, G. (Gyda); J.H. Brandsma (Johan); Pina Concas, M. (Maria); J. Derringer; Furlotte, N.A. (Nicholas A.); T.E. Galesloot (Tessel); S. Girotto; Gupta, R. (Richa); L.M. Hall (Leanne M.); S.E. Harris (Sarah); E. Hofer; Horikoshi, M. (Momoko); J.E. Huffman (Jennifer E.); Kaasik, K. (Kadri); I.-P. Kalafati (Ioanna-Panagiota); R. Karlsson (Robert); A. Kong (Augustine); J. Lahti (Jari); S.J. van der Lee (Sven); Deleeuw, C. (Christiaan); P.A. Lind (Penelope); Lindgren, K.-O. (Karl-Oskar); Liu, T. (Tian); M. Mangino (Massimo); J. Marten (Jonathan); E. Mihailov (Evelin); M. Miller (Mike); P.J. van der Most (Peter); C. Oldmeadow (Christopher); A. Payton (Antony); N. Pervjakova (Natalia); W.J. Peyrot (Wouter ); Qian, Y. (Yong); O. Raitakari (Olli); Rueedi, R. (Rico); Salvi, E. (Erika); Schmidt, B. (Börge); Schraut, K.E. (Katharina E.); Shi, J. (Jianxin); A.V. Smith (Albert Vernon); R.A. Poot (Raymond); B. St Pourcain (Beate); A. Teumer (Alexander); G. Thorleifsson (Gudmar); N. Verweij (Niek); D. Vuckovic (Dragana); Wellmann, J. (Juergen); H.J. Westra (Harm-Jan); Yang, J. (Jingyun); Zhao, W. (Wei); Zhu, Z. (Zhihong); B.Z. Alizadeh (Behrooz); N. Amin (Najaf); Bakshi, A. (Andrew); S.E. Baumeister (Sebastian); G. Biino (Ginevra); K. Bønnelykke (Klaus); P.A. Boyle (Patricia); H. Campbell (Harry); Cappuccio, F.P. (Francesco P.); G. Davies (Gail); J.E. de Neve (Jan-Emmanuel); P. Deloukas (Panagiotis); I. Demuth (Ilja); Ding, J. (Jun); Eibich, P. (Peter); Eisele, L. (Lewin); N. Eklund (Niina); D.M. Evans (David); J.D. Faul (Jessica D.); M.F. Feitosa (Mary Furlan); A.J. Forstner (Andreas); I. Gandin (Ilaria); Gunnarsson, B. (Bjarni); B.V. Halldorsson (Bjarni); T.B. Harris (Tamara); E.G. Holliday (Elizabeth); A.C. Heath (Andrew C.); L.J. Hocking; G. Homuth (Georg); M. Horan (Mike); J.J. Hottenga (Jouke Jan); P.L. de Jager (Philip); P.K. Joshi (Peter); A. Juqessur (Astanand); M. Kaakinen (Marika); M. Kähönen (Mika); S. Kanoni (Stavroula); Keltigangas-Järvinen, L. (Liisa); L.A.L.M. Kiemeney (Bart); I. Kolcic (Ivana); Koskinen, S. (Seppo); A. Kraja (Aldi); Kroh, M. (Martin); Z. Kutalik (Zoltán); A. Latvala (Antti); L.J. Launer (Lenore); Lebreton, M.P. (Maël P.); D.F. Levinson (Douglas F.); P. Lichtenstein (Paul); P. Lichtner (Peter); D.C. Liewald (David C.); A. Loukola (Anu); P.A. Madden (Pamela); R. Mägi (Reedik); Mäki-Opas, T. (Tomi); R.E. Marioni (Riccardo); P. Marques-Vidal; Meddens, G.A. (Gerardus A.); G. Mcmahon (George); C. Meisinger (Christa); T. Meitinger (Thomas); Milaneschi, Y. (Yusplitri); L. Milani (Lili); G.W. Montgomery (Grant); R. Myhre (Ronny); C.P. Nelson (Christopher P.); D.R. Nyholt (Dale); W.E.R. Ollier (William); A. Palotie (Aarno); L. Paternoster (Lavinia); N.L. Pedersen (Nancy); K. Petrovic (Katja); D.J. Porteous (David J.); K. Räikkönen (Katri); Ring, S.M. (Susan M.); A. Robino (Antonietta); O. Rostapshova (Olga); I. Rudan (Igor); A. Rustichini (Aldo); V. Salomaa (Veikko); Sanders, A.R. (Alan R.); A.-P. Sarin; R. Schmidt (Reinhold); R.J. Scott (Rodney); B.H. Smith (Blair); J.A. Smith (Jennifer A); J.A. Staessen (Jan); E. Steinhagen-Thiessen (Elisabeth); K. Strauch (Konstantin); A. Terracciano; M.D. Tobin (Martin); S. Ulivi (Shelia); S. Vaccargiu (Simona); L. Quaye (Lydia); F.J.A. van Rooij (Frank); C. Venturini (Cristina); A.A.E. Vinkhuyzen (Anna A.); U. Völker (Uwe); Völzke, H. (Henry); J.M. Vonk (Judith); D. Vozzi (Diego); J. Waage (Johannes); E.B. Ware (Erin B.); G.A.H.M. Willemsen (Gonneke); J. Attia (John); D.A. Bennett (David A.); Berger, K. (Klaus); L. Bertram (Lars); H. Bisgaard (Hans); D.I. Boomsma (Dorret); I.B. Borecki (Ingrid); U. Bültmann (Ute); C.F. Chabris (Christopher F.); F. Cucca (Francesco); D. Cusi (Daniele); I.J. Deary (Ian J.); G.V. Dedoussis (George); C.M. van Duijn (Cornelia); K. Hagen (Knut); B. Franke (Barbara); L. Franke (Lude); P. Gasparini (Paolo); P.V. Gejman (Pablo); C. Gieger (Christian); H.J. Grabe (Hans Jörgen); J. Gratten (Jacob); P.J.F. Groenen (Patrick); V. Gudnason (Vilmundur); P. van der Harst (Pim); C. Hayward (Caroline); D.A. Hinds (David A.); W. Hoffmann (Wolfgang); E. Hypponen (Elina); W.G. Iacono (William); B. Jacobsson (Bo); M.-R. Jarvelin (Marjo-Riitta); K.-H. JöCkel (Karl-Heinz); J. Kaprio (Jaakko); S.L.R. Kardia (Sharon); T. Lehtimäki (Terho); Lehrer, S.F. (Steven F.); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); A. Metspalu (Andres); N. Pendleton (Neil); B.W.J.H. Penninx (Brenda); M. Perola (Markus); N. Pirastu (Nicola); M. Pirastu (Mario); O. Polasek (Ozren); D. Posthuma (Danielle); C. Power (Christopher); M.A. Province (Mike); N.J. Samani (Nilesh); Schlessinger, D. (David); R. Schmidt (Reinhold); T.I.A. Sørensen (Thorkild); T.D. Spector (Timothy); J-A. Zwart (John-Anker); U. Thorsteinsdottir (Unnur); A.R. Thurik (Roy); Timpson, N.J. (Nicholas J.); H.W. Tiemeier (Henning); J.Y. Tung (Joyce Y.); A.G. Uitterlinden (André); Vitart, V. (Veronique); P. Vollenweider (Peter); D.R. Weir (David); J.F. Wilson (James F.); A.F. Wright (Alan); Conley, D.C. (Dalton C.); R.F. Krueger; G.D. Smith; Hofman, A. (Albert); D. Laibson (David); S.E. Medland (Sarah Elizabeth); M.N. Meyer (Michelle N.); J. Yang (Joanna); M. Johannesson (Magnus); P.M. Visscher (Peter); T. Esko (Tõnu); Ph.D. Koellinger (Philipp); D. Cesarini (David); D.J. Benjamin (Daniel J.)

    2016-01-01

    textabstractEducational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that

  10. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, A.; Beauchamp, J.; Fontana, M.A.; Lee, J.J.; Pers, T.H.; Rietveld, C.A.; Turley, P.; Chen, G.B.; Emilsson, V.; Meddens, S.F.W.; de Vlaming, R.; Abdellaoui, A.; Peyrot, W.; Vinkhuyzen, A.A.E.; Hottenga, J.J.; Willemsen, G.; Boomsma, D.I.; Penninx, B.W.J.H.; Laibson, D.; Medland, S.E.; Meyer, M.N.; Yang, J.; Johannesson, M.; Visscher, P.M.; Esko, T.; Koellinger, P.D.; Cesarini, D.; Benjamin, D.J.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our

  11. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark Alan; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; van der Most, Peter J.; Verweij, Niek; Alizadeh, Behrooz Z.; Vonk, Judith M.; Bultmann, Ute; Franke, Lude; van der Harst, Pim; Penninx, Brenda W. J. H.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends

  12. A prevalence-based association test for case-control studies.

    Science.gov (United States)

    Ryckman, Kelli K; Jiang, Lan; Li, Chun; Bartlett, Jacquelaine; Haines, Jonathan L; Williams, Scott M

    2008-11-01

    Genetic association is often determined in case-control studies by the differential distribution of alleles or genotypes. Recent work has demonstrated that association can also be assessed by deviations from the expected distributions of alleles or genotypes. Specifically, multiple methods motivated by the principles of Hardy-Weinberg equilibrium (HWE) have been developed. However, these methods do not take into account many of the assumptions of HWE. Therefore, we have developed a prevalence-based association test (PRAT) as an alternative method for detecting association in case-control studies. This method, also motivated by the principles of HWE, uses an estimated population allele frequency to generate expected genotype frequencies instead of using the case and control frequencies separately. Our method often has greater power, under a wide variety of genetic models, to detect association than genotypic, allelic or Cochran-Armitage trend association tests. Therefore, we propose PRAT as a powerful alternative method of testing for association.

  13. 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....

  14. Clinical study on antibody-associated limbic encephalitis

    Directory of Open Access Journals (Sweden)

    WANG Jia-wei

    2013-01-01

    Full Text Available In recent years, the antibody-associated limbic encephalitis (LE has attracted attentions of more and more clinicians. The associated antibodies mainly act on neuronal cell surface antigens, including the N-methyl-D-aspartate (NMDA receptor, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA receptor, the γ-aminobutyric acid B (GABAB receptor, leucine-rich glioma-inactivated 1 (LGI1 and contactin-associated protein-like 2 (Caspr2 and so on. The clinical manifestation is primarily defined by the subacute onset of short-term memory loss, seizures, confusion and psychiatric symptoms suggesting the involvement of the limbic system. These severe and protracted disorders can affect children and young adults, occurring with or without tumor association. Routine detection of serum and cerebrospinal fluid (CSF and imaging tests show no specificity, but associated antibodies can be detected in serum and (or CSF. The patients respond well to tumor resection and immunotherapies, including corticosteroids, intravenous immunoglobulin (IVIg, plasma exchange or combination of them, but may relapse. This article aims to study the clinical features and treatment of antibody-associated limbic encephalitis and to improve the diagnosis and prognosis of these diseases.

  15. 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.

  16. 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 ...

  17. Genome-wide association study identifies 74 loci associated with educational attainment

    OpenAIRE

    Okbay, Aysu; Beauchamp, Jonathan; Fontana, M.A. (Mark Alan); Lee, James J.; Pers, Tune; Rietveld, C.A. (Cornelius A.); Turley, Patrick; Chen, G.-B. (Guo-Bo); Emilsson, Valur; Meddens, S.F.W. (S. Fleur W.); Oskarsson, S. (Sven); Pickrell, J.K. (Joseph K.); Thom, K. (Kevin); Timshel, P. (Pascal); Vlaming, Ronald

    2016-01-01

    textabstractEducational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 geno...

  18. 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.

  19. Genome-Wide Association Study of Antiphospholipid Antibodies

    Directory of Open Access Journals (Sweden)

    M. Ilyas Kamboh

    2013-01-01

    Full Text Available Background. The persistent presence of antiphospholipid antibodies (APA may lead to the development of primary or secondary antiphospholipid syndrome. Although the genetic basis of APA has been suggested, the identity of the underlying genes is largely unknown. In this study, we have performed a genome-wide association study (GWAS in an effort to identify susceptibility loci/genes for three main APA: anticardiolipin antibodies (ACL, lupus anticoagulant (LAC, and anti-β2 glycoprotein I antibodies (anti-β2GPI. Methods. DNA samples were genotyped using the Affymetrix 6.0 array containing 906,600 single-nucleotide polymorphisms (SNPs. Association of SNPs with the antibody status (positive/negative was tested using logistic regression under the additive model. Results. We have identified a number of suggestive novel loci with Passociations of HLA genes and APOH with APA but these were not the top loci. Conclusions. We have identified a number of suggestive novel loci for APA that will stimulate follow-up studies in independent and larger samples to replicate our findings.

  20. Genome-wide association study identifies three novel genetic markers associated with elite endurance performance

    DEFF Research Database (Denmark)

    Ahmetov, Ii; Kulemin, Na; Popov, Dv

    2015-01-01

    To investigate the association between multiple single-nucleotide polymorphisms (SNPs), aerobic performance and elite endurance athlete status in Russians. By using GWAS approach, we examined the association between 1,140,419 SNPs and relative maximal oxygen consumption rate ([Formula: see text]O2......max) in 80 international-level Russian endurance athletes (46 males and 34 females). To validate obtained results, we further performed case-control studies by comparing the frequencies of the most significant SNPs (with P endurance athletes and opposite cohorts (192...... Russian controls, 1367 European controls, and 230 Russian power athletes). Initially, six 'endurance alleles' were identified showing discrete associations with [Formula: see text]O2max both in males and females. Next, case-control studies resulted in remaining three SNPs (NFIA-AS2 rs1572312, TSHR rs...

  1. 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

  2. To Be or Not to Be Associated: Power study of four statistical modeling approaches to identify parasite associations in cross-sectional studies

    Directory of Open Access Journals (Sweden)

    Elise eVaumourin

    2014-05-01

    Full Text Available A growing number of studies are reporting simultaneous infections by parasites in many different hosts. The detection of whether these parasites are significantly associated is important in medicine and epidemiology. Numerous approaches to detect associations are available, but only a few provide statistical tests. Furthermore, they generally test for an overall detection of association and do not identify which parasite is associated with which other one. Here, we developed a new approach, the association screening approach, to detect the overall and the detail of multi-parasite associations. We studied the power of this new approach and of three other known ones (i.e. the generalized chi-square, the network and the multinomial GLM approaches to identify parasite associations either due to parasite interactions or to confounding factors. We applied these four approaches to detect associations within two populations of multi-infected hosts: 1 rodents infected with Bartonella sp., Babesia microti and Anaplasma phagocytophilum and 2 bovine population infected with Theileria sp. and Babesia sp.. We found that the best power is obtained with the screening model and the generalized chi-square test. The differentiation between associations, which are due to confounding factors and parasite interactions was not possible. The screening approach significantly identified associations between Bartonella doshiae and B. microti, and between T. parva, T. mutans and T. velifera. Thus, the screening approach was relevant to test the overall presence of parasite associations and identify the parasite combinations that are significantly over- or under-represented. Unravelling whether the associations are due to real biological interactions or confounding factors should be further investigated. Nevertheless, in the age of genomics and the advent of new technologies, it is a considerable asset to speed up researches focusing on the mechanisms driving interactions

  3. Genome-wide association study identifies four loci associated with eruption of permanent teeth

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Zhang, Hao

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years......, analyzed as age-adjusted standard deviation score averaged over multiple time points, based on childhood records for 5,104 women from the Danish National Birth Cohort. Four loci showed association at P...

  4. Genome-Wide Association Study Identifies Four Loci Associated with Eruption of Permanent Teeth

    Science.gov (United States)

    Zhang, Hao; Shaffer, John R.; Hansen, Thomas; Esserlind, Ann-Louise; Boyd, Heather A.; Nohr, Ellen A.; Timpson, Nicholas J.; Fatemifar, Ghazaleh; Paternoster, Lavinia; Evans, David M.; Weyant, Robert J.; Levy, Steven M.; Lathrop, Mark; Smith, George Davey; Murray, Jeffrey C.; Olesen, Jes; Werge, Thomas; Marazita, Mary L.; Sørensen, Thorkild I. A.; Melbye, Mads

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, analyzed as age-adjusted standard deviation score averaged over multiple time points, based on childhood records for 5,104 women from the Danish National Birth Cohort. Four loci showed association at Peruption and were also known to influence height and breast cancer, respectively. The two other loci pointed to genomic regions without any previous significant genome-wide association study results. The intronic SNP rs7924176 in ADK could be linked to gene expression in monocytes. The combined effect of the four genetic variants was most pronounced between age 10 and 12 years, where children with 6 to 8 delayed tooth eruption alleles had on average 3.5 (95% confidence interval: 2.9–4.1) fewer permanent teeth than children with 0 or 1 of these alleles. PMID:21931568

  5. 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.

  6. Genome-wide association studies and resting heart rate

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas

    2016-01-01

    Genome-wide association studies (GWASs) have revolutionized the search for genetic variants regulating resting heart rate. In the last 10 years, GWASs have led to the identification of at least 21 novel heart rate loci. These discoveries have provided valuable insights into the mechanisms...... and pathways that regulate heart rate and link heart rate to cardiovascular morbidity and mortality. GWASs capture majority of genetic variation in a population sample by utilizing high-throughput genotyping chips measuring genotypes for up to several millions of SNPs across the genome in thousands...... of individuals. This allows the identification of the strongest heart rate associated signals at genome-wide level. While GWASs provide robust statistical evidence of the association of a given genetic locus with heart rate, they are only the starting point for detailed follow-up studies to locate the causal...

  7. 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.

  8. Genome-wide association studies in asthma: progress and pitfalls

    Directory of Open Access Journals (Sweden)

    March ME

    2015-01-01

    Full Text Available Michael E March,1 Patrick MA Sleiman,1,2 Hakon Hakonarson1,2 1Center for Applied Genomics, Children's Hospital of Philadelphia Research Institute, 2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Abstract: Genetic studies of asthma have revealed that there is considerable heritability to the phenotype. An extensive history of candidate-gene studies has identified a long list of genes associated with immune function that are potentially involved in asthma pathogenesis. However, many of the results of candidate-gene studies have failed to be replicated, leaving in question the true impact of the implicated biological pathways on asthma. With the advent of genome-wide association studies, geneticists are able to examine the association of hundreds of thousands of genetic markers with a phenotype, allowing the hypothesis-free identification of variants associated with disease. Many such studies examining asthma or related phenotypes have been published, and several themes have begun to emerge regarding the biological pathways underpinning asthma. The results of many genome-wide association studies have currently not been replicated, and the large sample sizes required for this experimental strategy invoke difficulties with sample stratification and phenotypic heterogeneity. Recently, large collaborative groups of researchers have formed consortia focused on asthma, with the goals of sharing material and data and standardizing diagnosis and experimental methods. Additionally, research has begun to focus on genetic variants that affect the response to asthma medications and on the biology that generates the heterogeneity in the asthma phenotype. As this work progresses, it will move asthma patients closer to more specific, personalized medicine. Keywords: asthma, genetics, GWAS, pharmacogenetics, biomarkers

  9. Genome-wide association study of clinical dimensions of schizophrenia

    DEFF Research Database (Denmark)

    Fanous, Ayman H; Zhou, Baiyu; Aggen, Steven H

    2012-01-01

    Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia.......Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia....

  10. Psychiatric disorders and obesity: A review of association studies

    Directory of Open Access Journals (Sweden)

    T M Rajan

    2017-01-01

    Full Text Available Background: Inconsistent evidence exists regarding the strength, direction, and moderators in the relationship between obesity and psychiatric disorders. Aim: This study aims to summarize the evidence on the association between psychiatric illness and obesity with particular attention to the strength and direction of association and also the possible moderators in each postulated link. Materials and Methods: Systematic electronic searches of MEDLINE through PubMed, ScienceDirect, PsycINFO, and Google Scholar were carried out from inception till October 2016. Generated abstracts were screened for eligibility to be included in the review. Study designs that evaluated the strength of relationship between obesity and psychiatric disorders were included in the study. Quality assessment of included studies was done using the Newcastle–Ottawa checklist tool. Results: From a total of 2424 search results, 21 eligible articles were identified and reviewed. These included studies on obesity and depression (n = 15, obesity and anxiety (four and one each on obesity and personality disorders, eating disorder (ED, attention deficit hyperactivity disorder, and alcohol use. Maximal evidence existed for the association between depression and obesity with longitudinal studies demonstrating a bidirectional link between the two conditions. The odds ratios (ORs were similar for developing depression in obesity (OR: 1.21–5.8 and vice versa (OR: 1.18–3.76 with a stronger association observed in women. For anxiety disorders, evidence was mostly cross-sectional, and associations were of modest magnitude (OR: 1.27–1.40. Among other disorders, obesity, and EDs appear to have a close link (OR: 4.5. Alcohol use appears to be a risk factor for obesity and not vice versa but only among women (OR: 3.84. Conclusion: Obesity and depression have a significant and bidirectional association. Evidence is modest for anxiety disorders and inadequate for other psychiatric

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

    Directory of Open Access Journals (Sweden)

    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

  12. Genome-Wide Association Studies of the Human Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Emily R Davenport

    Full Text Available The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both. These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%. For example, we identified an association between a taxon known to affect obesity (genus Akkermansia and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7. Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

  13. Associative visual agnosia: a case study.

    Science.gov (United States)

    Charnallet, A; Carbonnel, S; David, D; Moreaud, O

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study, an alternative account in the framework of (non abstractive) episodic models of memory.

  14. 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.

  15. 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

  16. 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.

  17. Microbiome-wide association studies link dynamic microbial consortia to disease

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, Jack A.; Quinn, Robert A.; Debelius, Justine; Xu, Zhenjiang Z.; Morton, James; Garg, Neha; Jansson, Janet K.; Dorrestein, Pieter C.; Knight, Rob

    2016-07-06

    Rapid advances in DNA sequencing, metabolomics, proteomics and computational tools are dramatically increasing access to the microbiome and identification of its links with disease. In particular, time-series studies and multiple molecular perspectives are facilitating microbiome-wide association studies, which are analogous to genome-wide association studies. Early findings point to actionable outcomes of microbiome-wide association studies, although their clinical application has yet to be approved. An appreciation of the complexity of interactions among the microbiome and the host's diet, chemistry and health, as well as determining the frequency of observations that are needed to capture and integrate this dynamic interface, is paramount for developing precision diagnostics and therapies that are based on the microbiome.

  18. Understanding Salesforce Behavior using Genetic Association Studies

    NARCIS (Netherlands)

    W.E. van den Berg (Wouter)

    2014-01-01

    markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of

  19. Associative Visual Agnosia: A Case Study

    Directory of Open Access Journals (Sweden)

    A. Charnallet

    2008-01-01

    Full Text Available We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive episodic models of memory [4].

  20. Associative Visual Agnosia: A Case Study

    OpenAIRE

    Charnallet, A.; Carbonnel, S.; David, D.; Moreaud, O.

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive) episodic models of memory [4].

  1. Genome-wide association studies (GWAS) of adiposity

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas; Ingelsson, Erik

    2016-01-01

    Adiposity is strongly heritable and one of the leading risk factors for type 2 diabetes, cardiovascular disease, cancer, and premature death. In the past 8 years, genome-wide association studies (GWAS) have greatly increased our understanding of the genes and biological pathways that regulate...

  2. Gastroschisis and associated defects: an international study.

    LENUS (Irish Health Repository)

    Mastroiacovo, Pierpaolo

    2007-04-01

    Our objective was to evaluate the frequency and type of malformations associated with gastroschisis in a large pool of international data, to identify malformation patterns, and to evaluate the role of maternal age in non-isolated cases. Case-by-case information from 24 registries, all members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), were evaluated. After the exclusion of other abdominal wall defects cases were classified as: (a) isolated; (b) recognizable syndrome, chromosomal or not; (c) multiple congenital anomalies (MCA). Our results showed that out of 3,322 total cases 469 non-isolated cases were registered (14.1%): 41 chromosomal syndromes, 24 other syndromes, and 404 MCA. Among MCA four groups of anomalies were most frequent: CNS (4.5%), cardio-vascular (2.5%), limb (2.2%), and kidney anomalies (1.9%). No similar patterns emerged except two patterns resembling limb-body wall complex and OEIS. In both of them the gastroschisis could be however misclassified. Chromosomal trisomies and possibly non-syndromic MCA are associated with an older maternal age more than isolated cases. On consideration of our data and the most valid studies published in the literature, the best estimate of the proportion of gastroschisis associated with major unrelated defects is about 10%, with a few cases associated to recognizable syndromes. Recognized syndromes with gastroschisis seem to be so exceptional that the well documented and validated cases are worth being published as interesting case report. An appropriate case definition in etiological studies should include only isolated gastroschisis after an appropriate definition of isolated and non-isolated cases and a thorough case-by-case review.

  3. A Genome-Wide Association Study Primer for Clinicians

    Directory of Open Access Journals (Sweden)

    Tzu-Hao Wang

    2009-06-01

    Full Text Available Genome-wide association studies (GWAS use high-throughput genotyping technology to relate hundreds of thousands of genetic markers (genotypes to clinical conditions and measurable traits (phenotypes. This review is intended to serve as an introduction to GWAS for clinicians, to allow them to better appreciate the value and limitations of GWAS for genotype-disease association studies. The input of clinicians is vital for GWAS, since disease heterogeneity is frequently a confounding factor that can only really be solved by clinicians. For diseases that are difficult to diagnose, clinicians should ensure that the cases do indeed have the disease; for common diseases, clinicians should ensure that the controls are truly disease-free.

  4. Type 1 diabetes genome-wide association studies

    DEFF Research Database (Denmark)

    Pociot, Flemming

    2017-01-01

    Genetic studies have identified >60 loci associated with the risk of developing type 1 diabetes (T1D). The vast majority of these are identified by genome-wide association studies (GWAS) using large case-control cohorts of European ancestry. More than 80% of the heritability of T1D can be explained...... by GWAS data in this population group. However, with few exceptions, their individual contribution to T1D risk is low and understanding their function in disease biology remains a huge challenge. GWAS on its own does not inform us in detail on disease mechanisms, but the combination of GWAS data...... with other omics-data is beginning to advance our understanding of T1D etiology and pathogenesis. Current knowledge supports the notion that genetic variation in both pancreatic β cells and in immune cells is central in mediating T1D risk. Advances, perspectives and limitations of GWAS are discussed...

  5. Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal.

    Science.gov (United States)

    Delgado, Dayana A; Zhang, Chenan; Chen, Lin S; Gao, Jianjun; Roy, Shantanu; Shinkle, Justin; Sabarinathan, Mekala; Argos, Maria; Tong, Lin; Ahmed, Alauddin; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Sarwar, Golam; Shahriar, Hasan; Rahman, Mahfuzar; Yunus, Mohammad; Jasmine, Farzana; Kibriya, Muhammad G; Ahsan, Habibul; Pierce, Brandon L

    2018-01-01

    Leucocyte telomere length (TL) is a potential biomarker of ageing and risk for age-related disease. Leucocyte TL is heritable and shows substantial differences by race/ethnicity. Recent genome-wide association studies (GWAS) report ~10 loci harbouring SNPs associated with leucocyte TL, but these studies focus primarily on populations of European ancestry. This study aims to enhance our understanding of genetic determinants of TL across populations. We performed a GWAS of TL using data on 5075 Bangladeshi adults. We measured TL using one of two technologies (qPCR or a Luminex-based method) and used standardised variables as TL phenotypes. Our results replicate previously reported associations in the TERC and TERT regions (P=2.2×10 -8 and P=6.4×10 -6 , respectively). We observed a novel association signal in the RTEL1 gene (intronic SNP rs2297439; P=2.82×10 -7 ) that is independent of previously reported TL-associated SNPs in this region. The minor allele for rs2297439 is common in South Asian populations (≥0.25) but at lower frequencies in other populations (eg, 0.07 in Northern Europeans). Among the eight other previously reported association signals, all were directionally consistent with our study, but only rs8105767 ( ZNF208 ) was nominally significant (P=0.003). SNP-based heritability estimates were as high as 44% when analysing close relatives but much lower when analysing distant relatives only. In this first GWAS of TL in a South Asian population, we replicate some, but not all, of the loci reported in prior GWAS of individuals of European ancestry, and we identify a novel second association signal at the RTEL1 locus. © 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Exome-wide association study of endometrial cancer in a multiethnic population.

    Directory of Open Access Journals (Sweden)

    Maxine M Chen

    Full Text Available Endometrial cancer (EC contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2. No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.

  9. Sincipital Encephaloceles: A Study of Associated Brain Malformations

    Directory of Open Access Journals (Sweden)

    Shashidhar Vedavyas Achar

    2016-01-01

    Full Text Available Objective: The aim of this study was to evaluate the associated intracranial malformations in patients with sincipital encephaloceles. Materials and Methods: A hospital-based cross-sectional study was conducted over 8 years from June 2007 to May 2015 on 28 patients. The patients were evaluated by either computed tomography or magnetic resonance imaging whichever was feasible. Encephaloceles were described with respect to their types, contents, and extensions. A note was made on the associated malformations with sincipital encephaloceles. Results: Fifty percent of the patients presented before the age of 3 years and both the sexes were affected equally. Nasofrontal encephalocele was the most common type seen in 13 patients (46.4%, and corpus callosal agenesis (12 patients was the most common associated malformation. Other malformations noted were arachnoid cyst (10 patients, hydrocephalus (7 patients, and agyria-pachygyria complex (2 patients. Conclusion: Capital Brain malformations are frequently encountered in children with sincipital encephaloceles. Detail radiological evaluation is necessary to plan treatment and also to prognosticate such rare malformations.

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

    Science.gov (United States)

    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

  11. Genome-wide association studies in Alzheimer's disease.

    Science.gov (United States)

    Bertram, Lars; Tanzi, Rudolph E

    2009-10-15

    Genome-wide association studies (GWAS) have gained considerable momentum over the last couple of years for the identification of novel complex disease genes. In the field of Alzheimer's disease (AD), there are currently eight published and two provisionally reported GWAS, highlighting over two dozen novel potential susceptibility loci beyond the well-established APOE association. On the basis of the data available at the time of this writing, the most compelling novel GWAS signal has been observed in GAB2 (GRB2-associated binding protein 2), followed by less consistently replicated signals in galanin-like peptide (GALP), piggyBac transposable element derived 1 (PGBD1), tyrosine kinase, non-receptor 1 (TNK1). Furthermore, consistent replication has been recently announced for CLU (clusterin, also known as apolipoprotein J). Finally, there are at least three replicated loci in hitherto uncharacterized genomic intervals on chromosomes 14q32.13, 14q31.2 and 6q24.1 likely implicating the existence of novel AD genes in these regions. In this review, we will discuss the characteristics and potential relevance to pathogenesis of the outcomes of all currently available GWAS in AD. A particular emphasis will be laid on findings with independent data in favor of the original association.

  12. Using Y-Chromosomal Haplogroups in Genetic Association Studies and Suggested Implications.

    Science.gov (United States)

    Erzurumluoglu, A Mesut; Baird, Denis; Richardson, Tom G; Timpson, Nicholas J; Rodriguez, Santiago

    2018-01-22

    Y-chromosomal (Y-DNA) haplogroups are more widely used in population genetics than in genetic epidemiology, although associations between Y-DNA haplogroups and several traits, including cardiometabolic traits, have been reported. In apparently homogeneous populations defined by principal component analyses, there is still Y-DNA haplogroup variation which will result from population history. Therefore, hidden stratification and/or differential phenotypic effects by Y-DNA haplogroups could exist. To test this, we hypothesised that stratifying individuals according to their Y-DNA haplogroups before testing for associations between autosomal single nucleotide polymorphisms (SNPs) and phenotypes will yield difference in association. For proof of concept, we derived Y-DNA haplogroups from 6537 males from two epidemiological cohorts, Avon Longitudinal Study of Parents and Children (ALSPAC) ( n = 5080; 816 Y-DNA SNPs) and the 1958 Birth Cohort ( n = 1457; 1849 Y-DNA SNPs), and studied the robust associations between 32 SNPs and body mass index (BMI), including SNPs in or near Fat Mass and Obesity-associated protein ( FTO ) which yield the strongest effects. Overall, no association was replicated in both cohorts when Y-DNA haplogroups were considered and this suggests that, for BMI at least, there is little evidence of differences in phenotype or SNP association by Y-DNA structure. Further studies using other traits, phenome-wide association studies (PheWAS), other haplogroups and/or autosomal SNPs are required to test the generalisability and utility of this approach.

  13. Prospective study of blood metabolites associated with colorectal cancer risk.

    Science.gov (United States)

    Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei

    2018-02-26

    Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.

  14. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger

    2009-01-01

    Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasiv...

  15. Replication of endometriosis-associated single-nucleotide polymorphisms from genome-wide association studies in a Caucasian population.

    Science.gov (United States)

    Sundqvist, J; Xu, H; Vodolazkaia, A; Fassbender, A; Kyama, C; Bokor, A; Gemzell-Danielsson, K; D'Hooghe, T M; Falconer, H

    2013-03-01

    Is it possible to replicate the previously identified genetic association of four single-nucleotide polymorphisms (SNPs), rs12700667, rs7798431, rs1250248 and rs7521902, with endometriosis in a Caucasian population? A borderline association was observed for rs1250248 and endometriosis (P = 0.049). However, we could not replicate the other previously identified endometriosis-associated SNPs (rs12700667, rs7798431 and rs7521902) in the same population. Endometriosis is considered a complex disease, influenced by several genetic and environmental factors, as well as interactions between them. Previous studies have found genetic associations with endometriosis for SNPs at the 7p15 and 2q35 loci in a Caucasian population. Allele frequencies of SNPs were investigated in patients with endometriosis and controls. Blood samples and peritoneal biopsies were taken from a Caucasian female population consisting of 1129 patients with endometriosis and 831 controls. DNA was extracted for genotyping. The study was performed at a University hospital and research laboratories. A weak association with endometriosis (all stages) was observed for rs1250248 (P = 0.049). No significant associations were observed for the SNPs rs12700667, rs7798431 and rs7521902. A non-significant trend towards the association of rs1250248 with moderate/severe endometriosis was observed (odds ratio 1.18, 95% confidence interval 0.97-1.44). The inability to confirm all previous findings may result from differences between populations and type II errors. Our result demonstrates the difficulty of identifying common genetic variants in complex diseases. This study was supported by grants from the Karolinska Institutet and Stockholm City County/Karolinska Institutet (ALF), Stockholm, Sweden, Swedish Medical Research Council (K2007-54X-14212-06-3, K2010-54X-14212-09-3), Stockholm, Sweden, Leuven University Research Council (Onderzoeksraad KU Leuven), the Leuven University Hospitals Clinical Research Foundation

  16. Toppar: an interactive browser for viewing association study results.

    Science.gov (United States)

    Juliusdottir, Thorhildur; Banasik, Karina; Robertson, Neil R; Mott, Richard; McCarthy, Mark I

    2018-06-01

    Data integration and visualization help geneticists make sense of large amounts of data. To help facilitate interpretation of genetic association data we developed Toppar, a customizable visualization tool that stores results from association studies and enables browsing over multiple results, by combining features from existing tools and linking to appropriate external databases. Detailed information on Toppar's features and functionality are on our website http://mccarthy.well.ox.ac.uk/toppar/docs along with instructions on how to download, install and run Toppar. Our online version of Toppar is accessible from the website and can be test-driven using Firefox, Safari or Chrome on sub-sets of publicly available genome-wide association study anthropometric waist and body mass index data (Locke et al., 2015; Shungin et al., 2015) from the Genetic Investigation of ANthropometric Traits consortium. totajuliusd@gmail.com.

  17. Lipid nanotechnologies for structural studies of membrane-associated proteins.

    Science.gov (United States)

    Stoilova-McPhie, Svetla; Grushin, Kirill; Dalm, Daniela; Miller, Jaimy

    2014-11-01

    We present a methodology of lipid nanotubes (LNT) and nanodisks technologies optimized in our laboratory for structural studies of membrane-associated proteins at close to physiological conditions. The application of these lipid nanotechnologies for structure determination by cryo-electron microscopy (cryo-EM) is fundamental for understanding and modulating their function. The LNTs in our studies are single bilayer galactosylceramide based nanotubes of ∼20 nm inner diameter and a few microns in length, that self-assemble in aqueous solutions. The lipid nanodisks (NDs) are self-assembled discoid lipid bilayers of ∼10 nm diameter, which are stabilized in aqueous solutions by a belt of amphipathic helical scaffold proteins. By combining LNT and ND technologies, we can examine structurally how the membrane curvature and lipid composition modulates the function of the membrane-associated proteins. As proof of principle, we have engineered these lipid nanotechnologies to mimic the activated platelet's phosphtaidylserine rich membrane and have successfully assembled functional membrane-bound coagulation factor VIII in vitro for structure determination by cryo-EM. The macromolecular organization of the proteins bound to ND and LNT are further defined by fitting the known atomic structures within the calculated three-dimensional maps. The combination of LNT and ND technologies offers a means to control the design and assembly of a wide range of functional membrane-associated proteins and complexes for structural studies by cryo-EM. The presented results confirm the suitability of the developed methodology for studying the functional structure of membrane-associated proteins, such as the coagulation factors, at a close to physiological environment. © 2014 Wiley Periodicals, Inc.

  18. Outcomes of Global Education: External and Internal Change Associated with Study Abroad

    Science.gov (United States)

    Miller-Perrin, Cindy; Thompson, Don

    2014-01-01

    This chapter provides an overview of external and internal changes associated with collegiate study abroad experiences. A brief review of the research literature is included along with recent research that sheds light on potential mechanisms associated with study abroad-related change. Recommendations for enhancing outcomes associated with study…

  19. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

    NARCIS (Netherlands)

    D.J. Gottlieb (Daniel J); K. Hek (Karin); T.-H. Chen; N.F. Watson; G. Eiriksdottir (Gudny); E.M. Byrne; M. Cornelis (Marilyn); S.C. Warby; S. Bandinelli; L. Cherkas (Lynn); D.S. Evans (Daniel); H.J. Grabe (Hans Jörgen); J. Lahti (Jari); M. Li (Man); T. Lehtimäki (Terho); T. Lumley (Thomas); K. Marciante (Kristin); L. Perusse (Louis); B.M. Psaty (Bruce); J. Robbins; G.J. Tranah (Gregory); J.M. Vink; J.B. Wilk; J.M. Stafford; C. Bellis (Claire); R. Biffar; C. Bouchard (Claude); B. Cade; G.C. Curhan (Gary); J. Eriksson; R. Ewert; L. Ferrucci (Luigi); T. Fülöp; P.R. Gehrman (Philip); R. Goodloe (Robert); T.B. Harris (Tamara); A.C. Heath (Andrew C.); D.G. Hernandez (Dena); A. Hofman (Albert); J.J. Hottenga (Jouke Jan); D. Hunter (David); M.K. Jensen (Majken K.); A.D. Johnson (Andrew); M. Kähönen (Mika); W.H.L. Kao (Wen); P. Kraft (Peter); E.K. Larkin; D.S. Lauderdale; A.I. Luik (Annemarie I); M. Medici; G.W. Montgomery (Grant W.); A. Palotie; S.R. Patel (Sanjay); G. Pistis (Giorgio); E. Porcu; L. Quaye (Lydia); O. Raitakari (Olli); S. Redline (Susan); E.B. Rimm (Eric B.); J.I. Rotter; A.V. Smith; T.D. Spector (Timothy); A. Teumer (Alexander); A.G. Uitterlinden (André); M.-C. Vohl (Marie-Claude); E. Widen; G.A.H.M. Willemsen (Gonneke); T.L. Young (Terri L.); X. Zhang; Y. Liu; J. Blangero (John); D.I. Boomsma (Dorret); V. Gudnason (Vilmundur); F. Hu; M. Mangino; N.G. Martin (Nicholas); G.T. O'Connor (George); K.L. Stone (Katie L); T. Tanaka; J. Viikari (Jorma); S.A. Gharib (Sina); N.M. Punjabi (Naresh); K. Räikkönen (Katri); H. Völzke (Henry); E. Mignot; H.W. Tiemeier (Henning)

    2015-01-01

    textabstractUsual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18

  20. Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans

    Directory of Open Access Journals (Sweden)

    Kidambi Srividya

    2012-04-01

    Full Text Available Abstract Background A recent genome wide association study in 1017 African Americans identified several single nucleotide polymorphisms that reached genome-wide significance for systolic blood pressure. We attempted to replicate these findings in an independent sample of 2474 unrelated African Americans in the Milwaukee metropolitan area; 53% were women and 47% were hypertensives. Methods We evaluated sixteen top associated SNPs from the above genome wide association study for hypertension as a binary trait or blood pressure as a continuous trait. In addition, we evaluated eight single nucleotide polymorphisms located in two genes (STK-39 and CDH-13 found to be associated with systolic and diastolic blood pressures by other genome wide association studies in European and Amish populations. TaqMan MGB-based chemistry with fluorescent probes was used for genotyping. We had an adequate sample size (80% power to detect an effect size of 1.2-2.0 for all the single nucleotide polymorphisms for hypertension as a binary trait, and 1% variance in blood pressure as a continuous trait. Quantitative trait analyses were performed both by excluding and also by including subjects on anti-hypertensive therapy (after adjustments were made for anti-hypertensive medications. Results For all 24 SNPs, no statistically significant differences were noted in the minor allele frequencies between cases and controls. One SNP (rs2146204 showed borderline association (p = 0.006 with hypertension status using recessive model and systolic blood pressure (p = 0.02, but was not significant after adjusting for multiple comparisons. In quantitative trait analyses, among normotensives only, rs12748299 was associated with SBP (p = 0.002. In addition, several nominally significant associations were noted with SBP and DBP among normotensives but none were statistically significant. Conclusions This study highlights the importance of replication to confirm the validity of genome wide

  1. Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study

    NARCIS (Netherlands)

    Gottlieb, D.J.; Hek, K.; Chen, T.H.; Watson, N.F.; Eiriksdottir, G.; Byrne, E.M.; Cornelis, M.; Warby, S.C.; Bandinelli, S.; Cherkas, L.; Evans, D.S.; Grabe, H.J.; Lahti, J.; Li, M.; Lehtimäki, T.; Lumley, T.; Marciante, K.; Pérusse, L.; Psaty, B.M.; Robbins, J.; Tranah, G.; Vink, J.M.; Wilk, J.B.; Stafford, J.M.; Bellis, M.; Biffar, R.; Bouchard, C.; Cade, B.; Curhan, G.C.; Eriksson, J.G.; Ewert, R.; Ferrucci, L.; Fülöp, T.; Gehrman, P.R.; Goodloe, R.; Harris, T.B.; Heath, A.C.; Hernandez, D.; Hofman, A.; Hottenga, J.J.; Hunter, D.J.; Jensen, M.K.; Johnson, A.D.; Kähönen, M.; Kao, L.; Kraft, P.; Larkin, E.K.; Lauderdale, D.S.; Luik, A.I.; Medici, M.; Montgomery, G.W.; Palotie, A.; Patel, S.R.; Pistis, G.; Porcu, E.; Quaye, L.; Raitakari, O.; Redline, S.; Rimm, E.B.; Rotter, J.I.; Smith, A.V.; Spector, T.D.; Teumer, A.; Uitterlinden, A.G.; Vohl, M.-C.; Widén, E.; Willemsen, G.; Young, T.; Zhang, X.; Liu, Y.; Blanger, J.; Boomsma, D.I.; Gudnason, V.; Hu, F.; Mangino, M.; Martin, N.G.; O'Connor, G.T.; Stone, K.L.; Tanaka, T.; Viikari, J.; Gharib, S.A.; Punjabi, N.M.; Räikkönen, K.; Völzke, H.; Mignot, E.; Tiemeier, H.

    2015-01-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based

  2. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and

  3. A genome-wide association study of attempted suicide

    Science.gov (United States)

    Willour, Virginia L.; Seifuddin, Fayaz; Mahon, Pamela B.; Jancic, Dubravka; Pirooznia, Mehdi; Steele, Jo; Schweizer, Barbara; Goes, Fernando S.; Mondimore, Francis M.; MacKinnon, Dean F.; Perlis, Roy H.; Lee, Phil Hyoun; Huang, Jie; Kelsoe, John R.; Shilling, Paul D.; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Purcell, Shaun; Smoller, Jordan W.; Craddock, Nicholas; DePaulo, J. Raymond; Schulze, Thomas G.; McMahon, Francis J.; Zandi, Peter P.; Potash, James B.

    2011-01-01

    The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. While attempted suicide linkage regions have been identified on 2p11–12 and 6q25–26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single nucleotide polymorphism (SNP) genotypes of 1,201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1,497 BP subjects without a history of suicide attempts. 2,507 SNPs with evidence for association at p<0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (p= 5.07 × 10−8). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide. PMID:21423239

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

    Directory of Open Access Journals (Sweden)

    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.

  5. An Entropy-Based Statistic for Genomewide Association Studies

    OpenAIRE

    Zhao, Jinying; Boerwinkle, Eric; Xiong, Momiao

    2005-01-01

    Efficient genotyping methods and the availability of a large collection of single-nucleotide polymorphisms provide valuable tools for genetic studies of human disease. The standard χ2 statistic for case-control studies, which uses a linear function of allele frequencies, has limited power when the number of marker loci is large. We introduce a novel test statistic for genetic association studies that uses Shannon entropy and a nonlinear function of allele frequencies to amplify the difference...

  6. 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....

  7. A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype.

    Directory of Open Access Journals (Sweden)

    Johanna Hass

    Full Text Available Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we combined genetics, imaging and neuropsychological data obtained from the Mind Clinical Imaging Consortium study of schizophrenia (n = 328. A total of 743,591 SNPs were tested for association with hippocampal volume in a genome-wide association study. Gene expression profiles of human hippocampal tissue were investigated for gene regions of significantly associated SNPs. None of the genetic markers reached genome-wide significance. However, six highly correlated SNPs (rs4808611, rs35686037, rs12982178, rs1042178, rs10406920, rs8170 on chromosome 19p13.11, located within or in close proximity to the genes NR2F6, USHBP1, and BABAM1, as well as four SNPs in three other genomic regions (chromosome 1, 2 and 10 had p-values between 6.75×10(-6 and 8.3×10(-7. Using existing data of a very recently published GWAS of hippocampal volume and additional data of a multicentre study in a large cohort of adolescents of European ancestry, we found supporting evidence for our results. Furthermore, allelic differences in rs4808611 and rs8170 were highly associated with differential mRNA expression in the cis-acting region. Associations with memory functioning indicate a possible functional importance of the identified risk variants. Our findings provide new insights into the genetic architecture of a brain structure closely linked to schizophrenia. In silico replication, mRNA expression and cognitive data provide additional support for the relevance of our findings

  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. The Cultural Roots of Teacher Associations: A Case Study from India

    Science.gov (United States)

    Padwad, Amol

    2016-01-01

    Teacher associations (TAs) are communities located in complex cultural spaces that may affect their functioning, vision, priorities, and policies. This case study of the English Language Teachers' Association of India (ELTAI) attempts to examine the relationship between the Association and the cultural space it inhabits, with specific reference to…

  10. 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.

  11. Microbiome-wide association studies link dynamic microbial consortia to disease

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, Jack A.; Quinn, Robert A.; Debelius, Justine; Xu, Zhenjiang Z.; Morton, James; Garg, Neha; Jansson, Janet K.; Dorrestein, Pieter C.; Knight, Rob

    2016-07-06

    Rapid advances in DNA sequencing, metabolomics, proteomics and computation dramatically increase accessibility of microbiome studies and identify links between the microbiome and disease. Microbial time-series and multiple molecular perspectives enable Microbiome-Wide Association Studies (MWAS), analogous to Genome-Wide Association Studies (GWAS). Rapid research advances point towards actionable results, although approved clinical tests based on MWAS are still in the future. Appreciating the complexity of interactions between diet, chemistry, health and the microbiome, and determining the frequency of observations needed to capture and integrate this dynamic interface, is paramount for addressing the need for personalized and precision microbiome-based diagnostics and therapies.

  12. 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

  13. Genome-wide association study of pancreatic cancer in Japanese population.

    Directory of Open Access Journals (Sweden)

    Siew-Kee Low

    Full Text Available Pancreatic cancer shows very poor prognosis and is the fifth leading cause of cancer death in Japan. Previous studies indicated some genetic factors contributing to the development and progression of pancreatic cancer; however, there are limited reports for common genetic variants to be associated with this disease, especially in the Asian population. We have conducted a genome-wide association study (GWAS using 991 invasive pancreatic ductal adenocarcinoma cases and 5,209 controls, and identified three loci showing significant association (P-value<5x10(-7 with susceptibility to pancreatic cancer. The SNPs that showed significant association carried estimated odds ratios of 1.29, 1.32, and 3.73 with 95% confidence intervals of 1.17-1.43, 1.19-1.47, and 2.24-6.21; P-value of 3.30x10(-7, 3.30x10(-7, and 4.41x10(-7; located on chromosomes 6p25.3, 12p11.21 and 7q36.2, respectively. These associated SNPs are located within linkage disequilibrium blocks containing genes that have been implicated some roles in the oncogenesis of pancreatic cancer.

  14. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Common genetic variants associated with disease from genome-wide association studies are mutually exclusive in prostate cancer and rheumatoid arthritis.

    Science.gov (United States)

    Orozco, Gisela; Goh, Chee L; Al Olama, Ali Amin; Benlloch-Garcia, Sara; Govindasami, Koveela; Guy, Michelle; Muir, Kenneth R; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Kote-Jarai, Zsofia; Easton, Douglas F; Eyre, Steve; Eeles, Rosalind A

    2013-06-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The link between inflammation and cancer has long been reported and inflammation is thought to play a role in the pathogenesis of many cancers, including prostate cancer (PrCa). Over the last 5 years, genome-wide association studies (GWAS) have reported numerous susceptibility loci that predispose individuals to many different traits. The present study aims to ascertain if there are common genetic risk profiles that might predispose individuals to both PrCa and the autoimmune inflammatory condition, rheumatoid arthritis. These results could have potential public heath impact in terms of screening and chemoprevention. To investigate if potential common pathways exist for the pathogenesis of autoimmune disease and prostate cancer (PrCa). To ascertain if the single nucleotide polymorphisms (SNPs) reported by genome-wide association studies (GWAS) as being associated with susceptibility to PrCa are also associated with susceptibility to the autoimmune disease rheumatoid arthritis (RA). The original Wellcome Trust Case Control Consortium (WTCCC) UK RA GWAS study was expanded to include a total of 3221 cases and 5272 controls. In all, 37 germline autosomal SNPs at genome-wide significance associated with PrCa risk were identified from a UK/Australian PrCa GWAS. Allele frequencies were compared for these 37 SNPs between RA cases and controls using a chi-squared trend test and corrected for multiple testing (Bonferroni). In all, 33 SNPs were able to be analysed in the RA dataset. Proxies could not be located for the SNPs in 3q26, 5p15 and for two SNPs in 17q12. After applying a Bonferroni correction for the number of SNPs tested, the SNP mapping to CCHCR1 (rs130067) retained statistically significant evidence for association (P = 6 × 10(-4) ; odds ratio [OR] = 1.15, 95% CI: 1.06-1.24); this has also been associated with psoriasis. However, further analyses showed that the association of this allele was due to

  17. Study on drug costs associated with COPD prescription medicine in Denmark

    DEFF Research Database (Denmark)

    Jakobsen, M; Anker, N; Dollerup, J

    2013-01-01

    that the costs associated with COPD in Denmark are significant, but costs of prescription medicine for COPD were not analysed. OBJECTIVES: To analyse the societal costs associated with prescription medicine for COPD in Denmark. METHODS: The study was designed as a nationwide retrospective register study...... in 2010 with total costs of DKK 685 million (EUR 92 million). The average lifetime costs associated with COPD prescription medicine were estimated to be DKK 70,000-75,000 (EUR 9,416-10,089) per patient (2010 prices). CONCLUSION: The costs associated with prescription medicine for COPD in Denmark...... of the drug costs (ATC group R03) associated with COPD in the period 2001-2010. Data were retrieved from the Prescription Database, the National Patient Register and the Centralised Civil Register. The population comprised individuals (40+ years) who had at least one prescription of selected R03 drugs and who...

  18. STUDY ON DRUG COSTS ASSOCIATED WITH COPD PRESCRIPTION MEDICINE IN DENMARK

    DEFF Research Database (Denmark)

    Jakobsen, Iris Marie; Anker, Niels; Dolleru, Jens

    2012-01-01

    that the costs associated with COPD in Denmark are significant, but costs of prescription medicine for COPD were not analysed. OBJECTIVES: To analyse the societal costs associated with prescription medicine for COPD in Denmark. METHODS: The study was designed as a nationwide retrospective register study...... in 2010 with total costs of DKK 685 million (EUR 92 million). The average lifetime costs associated with COPD prescription medicine were estimated to be DKK 70,000-75,000 (EUR 9,416-10,089) per patient (2010 prices). CONCLUSION: The costs associated with prescription medicine for COPD in Denmark...... of the drug costs (ATC group R03) associated with COPD in the period 2001-2010. Data were retrieved from the Prescription Database, the National Patient Register and the Centralised Civil Register. The population comprised individuals (40+ years) who had at least one prescription of selected R03 drugs and who...

  19. A genetic association study of the IGF-1 gene and radiological osteoarthritis in a population-based cohort study (the Rotterdam study)

    NARCIS (Netherlands)

    Meulenbelt, I.; Bijkerk, C.; Miedema, H.S.; Breedveld, F.C.; Hofman, A.; Valkenburg, H.A.; Pols, H.A.P.; Slagboom, P.E.; Duijn, C.M. van

    1998-01-01

    Objective - A genetic association study was performed to investigate whether radiographical osteoarthritis (ROA) was associated with specific genotypes of the insulin-like growth factor I (IGF-1) gene. Methods - Subjects aged 55-65 years were selected from a population-based study of which ROA at

  20. Study on drug costs associated with COPD prescription medicine in Denmark.

    Science.gov (United States)

    Jakobsen, Marie; Anker, Niels; Dollerup, Jens; Poulsen, Peter Bo; Lange, Peter

    2013-10-01

    Spirometric studies of the general population estimate that 430 000 Danes have chronic obstructive pulmonary disease (COPD). COPD is mainly caused by smoking, and smoking cessation is the most important intervention to prevent disease progression. Cost-of-illness studies conclude that the costs associated with COPD in Denmark are significant, but costs of prescription medicine for COPD were not analysed. To analyse the societal costs associated with prescription medicine for COPD in Denmark. The study was designed as a nationwide retrospective register study of the drug costs (ATC group R03) associated with COPD in the period 2001-2010. Data were retrieved from the Prescription Database, the National Patient Register and the Centralised Civil Register. The population comprised individuals (40+ years) who had at least one prescription of selected R03 drugs and who had been either hospitalised with a COPD diagnosis or had at least one prescription for drugs primarily used for COPD. The study population comprised 166 462 individuals of which 97 916 were alive on 31 December 2010. The average annual drug costs (R03) were DKK 7842 (EUR 1055) per patient in 2010 with total costs of DKK 685 million (EUR 92 million). The average lifetime costs associated with COPD prescription medicine were estimated to be DKK 70 000-75 000 (EUR 9416-10 089) per patient (2010 prices). The costs associated with prescription medicine for COPD in Denmark are significant. © 2012 John Wiley & Sons Ltd.

  1. Association of Torsion With Testicular Cancer: A Retrospective Study.

    Science.gov (United States)

    Uguz, Sami; Yilmaz, Sercan; Guragac, Ali; Topuz, Bahadır; Aydur, Emin

    2016-02-01

    Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported with the association of torsion in surgical specimens, and the published data remain scant on the association of torsion with testicular tumors. By retrospective medical record review, we identified 32 patients who had been diagnosed with testicular torsion, 20 of whom had undergone orchiectomy. Of these 20 patients, 2 were diagnosed with a malignancy. Our study, the largest case series to date, has shown an association between testicular torsion and testicular cancer of 6.4%. Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported in association with torsion in surgical specimens. However, the published data remain scant on the association between torsion and the presence of testicular tumors. The present retrospective study explored the association between torsion and testicular cancer in patients with testicular torsion undergoing orchiectomy during scrotal exploration. A medical record review was performed of patients who had had a diagnosis of testicular torsion from January 2003 to February 2015. The clinicopathologic characteristics of the patients were recorded. A total of 32 patients were identified. Their mean age was 21.1 years (range, 7-39 years). All the patients had unilateral testicular torsion, which affected the left side in 17 and the right side in 15. Manual detorsion was successful in 6 patients, and 26 patients underwent emergency surgery with testicular detorsion (6 fixation surgery and 20 orchiectomy). The type of incision was scrotal in 6, inguinal in 10, and unspecified in 4. Pathologic examination of the orchiectomy specimens showed malignancy in 2 cases (seminoma and malign mixed germ cell tumor). To the best of our knowledge, the present single-center case series is the largest case series to date of

  2. Genome-wide association study of suicide attempts in mood disorder patients.

    Science.gov (United States)

    Perlis, Roy H; Huang, Jie; Purcell, Shaun; Fava, Maurizio; Rush, A John; Sullivan, Patrick F; Hamilton, Steven P; McMahon, Francis J; Schulze, Thomas G; Schulze, Thomas; Potash, James B; Zandi, Peter P; Willour, Virginia L; Penninx, Brenda W; Boomsma, Dorret I; Vogelzangs, Nicole; Middeldorp, Christel M; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Bass, Nick; McQuillin, Andrew; Hamshere, Marian; Craddock, Nick; Sklar, Pamela; Smoller, Jordan W

    2010-12-01

    Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.

  3. 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.

  4. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study

    NARCIS (Netherlands)

    A. Dehghan (Abbas); A. Köttgen (Anna); Q. Yang (Qiong Fang); S.J. Hwang; W.H.L. Kao (Wen); F. Rivadeneira Ramirez (Fernando); E.A. Boerwinkle (Eric); D. Levy (Daniel); A. Hofman (Albert); B.C. Astor (Brad); E.J. Benjamin (Emelia); P. Tikka-Kleemola (Päivi); J.C.M. Witteman (Jacqueline); J. Coresh (Josef); C.S. Fox (Caroline)

    2008-01-01

    textabstractBackground: Hyperuricaemia, a highly heritable trait, is a key risk factor for gout. We aimed to identify novel genes associated with serum uric acid concentration and gout. Methods: Genome-wide association studies were done for serum uric acid in 7699 participants in the Framingham

  5. Genome-wide association study of autistic-like traits in a general population study of young adults

    Directory of Open Access Journals (Sweden)

    Rachel Maree Jones

    2013-10-01

    Full Text Available Research has proposed that autistic-like traits in the general population lie on a continuum, with clinical Autism Spectrum Disorder (ASD representing the extreme end of this distribution. Inherent in this proposal is that biological mechanisms associated with clinical ASD may also underpin variation in autistic-like traits within the general population. A genome-wide association study using 2,462,046 single nucleotide polymorphisms (SNPs was undertaken for ASD in 965 individuals from the Western Australian Pregnancy Cohort (Raine Study. No SNP associations reached genome-wide significance (p < 5.0 x 10-8. However, investigations into nominal observed SNP associations (p < 1.0 x 10-5 add support to two positional candidate genes previously implicated in ASD aetiology, PRKCB1 and CBLN1.The rs198198 SNP (p = 9.587 x 10-6, is located within an intron of the protein kinase C, beta 1 (PRKCB1 gene on chromosome 16p11. The PRKCB1 gene has been previously reported in linkage and association studies for ASD, and its mRNA expression has been shown to be significantly down regulated in ASD cases compared with controls. The rs16946931 SNP (p = 1.78 x 10-6 is located in a region flanking the Cerebellin 1 (CBLN1 gene on chromosome 16q12.1. The CBLN1 gene is involved with synaptogenesis and is part of a gene family previously implicated in ASD. This GWA study is only the second to examine SNPs associated with autistic-like traits in the general population, and provides evidence to support roles for the PRKCB1 and CBLN1 genes in risk of clinical ASD.

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

    Science.gov (United States)

    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/ .

  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.

    Directory of Open Access Journals (Sweden)

    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. 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.

  9. Intent inferencing by an intelligent operator's associate - A validation study

    Science.gov (United States)

    Jones, Patricia M.

    1988-01-01

    In the supervisory control of a complex, dynamic system, one potential form of aiding for the human operator is a computer-based operator's associate. The design philosophy of the operator's associate is that of 'amplifying' rather than automating human skills. In particular, the associate possesses understanding and control properties. Understanding allows it to infer operator intentions and thus form the basis for context-dependent advice and reminders; control properties allow the human operator to dynamically delegate individual tasks or subfunctions to the associate. This paper focuses on the design, implementation, and validation of the intent inferencing function. Two validation studies are described which empirically demonstrate the viability of the proposed approach to intent inferencing.

  10. Genome-wide association studies of obesity and metabolic syndrome.

    Science.gov (United States)

    Fall, Tove; Ingelsson, Erik

    2014-01-25

    Until just a few years ago, the genetic determinants of obesity and metabolic syndrome were largely unknown, with the exception of a few forms of monogenic extreme obesity. Since genome-wide association studies (GWAS) became available, large advances have been made. The first single nucleotide polymorphism robustly associated with increased body mass index (BMI) was in 2007 mapped to a gene with for the time unknown function. This gene, now known as fat mass and obesity associated (FTO) has been repeatedly replicated in several ethnicities and is affecting obesity by regulating appetite. Since the first report from a GWAS of obesity, an increasing number of markers have been shown to be associated with BMI, other measures of obesity or fat distribution and metabolic syndrome. This systematic review of obesity GWAS will summarize genome-wide significant findings for obesity and metabolic syndrome and briefly give a few suggestions of what is to be expected in the next few years. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Genome-Wide Association Study for Nine Plant Architecture Traits in Sorghum

    Directory of Open Access Journals (Sweden)

    Jing Zhao

    2016-07-01

    Full Text Available Sorghum [ (L Moench], an important grain and forage crop, is receiving significant attention as a lignocellulosic feedstock because of its water-use efficiency and high biomass yield potential. Because of the advancement of genotyping and sequencing technologies, genome-wide association study (GWAS has become a routinely used method to investigate the genetic mechanisms underlying natural phenotypic variation. In this study, we performed a GWAS for nine grain and biomass-related plant architecture traits to determine their overall genetic architecture and the specific association of allelic variants in gibberellin (GA biosynthesis and signaling genes with these phenotypes. A total of 101 single-nucleotide polymorphism (SNP representative regions were associated with at least one of the nine traits, and two of the significant markers correspond to GA candidate genes, ( and (, affecting plant height and seed number, respectively. The resolution of a previously reported quantitative trait loci (QTL for leaf angle on chromosome 7 was increased to a 1.67 Mb region containing seven candidate genes with good prospects for further investigation. This study provides new knowledge of the association of GA genes with plant architecture traits and the genomic regions controlling variation in leaf angle, stem circumference, internode number, tiller number, seed number, panicle exsertion, and panicle length. The GA gene affecting seed number variation ( and the genomic region on chromosome 7 associated with variation in leaf angle are also important outcomes of this study and represent the foundation of future validation studies needed to apply this knowledge in breeding programs.

  12. Known glioma risk loci are associated with glioma with a family history of brain tumours -- a case-control gene association study.

    Science.gov (United States)

    Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika; Wang, Zhaoming; Henriksson, Roger; Hallmans, Göran; Bondy, Melissa L; Johansen, Christoffer; Feychting, Maria; Ahlbom, Anders; Kitahara, Cari M; Wang, Sophia S; Ruder, Avima M; Carreón, Tania; Butler, Mary Ann; Inskip, Peter D; Purdue, Mark; Hsing, Ann W; Mechanic, Leah; Gillanders, Elizabeth; Yeager, Meredith; Linet, Martha; Chanock, Stephen J; Hartge, Patricia; Rajaraman, Preetha

    2013-05-15

    Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted ptrend , 1.7 × 10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours. Copyright © 2012 UICC.

  13. An association study of suicide and candidate genes in the serotonergic system

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette N; Flint, Tracey J; Foldager, Leslie

    2013-01-01

    Introduction: Strong evidence demonstrates a genetic susceptibility to suicidal behaviour and a relationship between suicide and mental disorders. The aim of this study was to test for association between suicide and five selected genetic variants, which had shown association with suicide in other...... populations. Method: We performed a nationwide case-control study on all suicide cases sent for autopsy in Denmark between the years 2000 and 2007. The study comprised 572 cases and 1049 controls and is one of the largest genetic studies in completed suicide to date. The analysed markers were located within...... the Serotonin Transporter (SLC6A4), Monoamine Oxidase-A (MAOA) and the Ttyptophan Hydroxylase I and II (TPH1 and TPH2) genes. Results: None of the genetic markers within SLC6A4, MAOA, TPH1 and TPH2 were significantly associated with completed suicide or suicide method in the basic association tests. Exploratory...

  14. Genome-wide association study identifies a novel canine glaucoma locus.

    Directory of Open Access Journals (Sweden)

    Saija J Ahonen

    Full Text Available Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its hereditary forms are classified into primary closed-angle (PCAG, primary open-angle (POAG and primary congenital glaucoma (PCG. Although many loci have been mapped in human, only a few genes have been identified that are associated with the development of glaucoma and the genetic basis of the disease remains poorly understood. Glaucoma has also been described in many dog breeds, including Dandie Dinmont Terriers (DDT in which it is a late-onset (>7 years disease. We designed clinical and genetic studies to better define the clinical features of glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was based on ophthalmic examinations of the affected dogs and 18 additionally investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome wide association study was performed in a cohort of 23 affected and 23 controls, followed by a fine mapping, a replication study and candidate gene sequencing. The clinical study suggested that ocular abnormalities including abnormal iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%, respectively in the breed and the disease resembles human PCAG. The genetic study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb best associated region (p = 1.63 × 10(-10, OR = 32 for homozygosity. Mutation screening in five candidate genes did not reveal any causative variants. This study indicates that although ocular abnormalities are common in DDTs, the genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus shares synteny to a region in human chromosome 14q, which harbors several loci associated with POAG and PCG. Our study reveals a new locus for canine glaucoma and ongoing molecular studies will likely help to understand the genetic etiology of the disease.

  15. Association study between schizophrenia and dopamine D3 receptor gene polymorphism

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Toshihisa; Takahashi, Makoto; Maeda, Masaya [Niigata Univ. (Japan)] [and others

    1996-07-26

    Crocq et al. reported the existence of an association between schizophrenia and homozygosity of a BalI polymorphism in the first exon of the dopamine D3 receptor (DRD3) gene. In response to this report, further studies were conducted; however, these studies yielded conflicting results. In the present study, we examined 100 unrelated Japanese schizophrenics and 100 normal controls to determine any association between this polymorphism and schizophrenia. Results suggest that neither allele nor genotype frequencies of the DRD3 gene in the schizophrenics as a whole are significantly different from those of the controls. Further, we found no association between any allele or genotype and any clinical subtype based on family history of schizophrenia and age-at-onset. A significantly high frequency of homozygosity of a dopamine D3 receptor gene allele was not observed in the schizophrenics as a whole, or in clinical subtypes. Our results suggest that an association between the dopamine D3 receptor gene and schizophrenia is unlikely to exist. 26 refs., 1 tab.

  16. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Directory of Open Access Journals (Sweden)

    Varun Warrier

    Full Text Available Asperger Syndrome (AS is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC, which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448 were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448 lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  17. Challenges in reproducibility of genetic association studies: lessons learned from the obesity field.

    Science.gov (United States)

    Li, A; Meyre, D

    2013-04-01

    A robust replication of initial genetic association findings has proved to be difficult in human complex diseases and more specifically in the obesity field. An obvious cause of non-replication in genetic association studies is the initial report of a false positive result, which can be explained by a non-heritable phenotype, insufficient sample size, improper correction for multiple testing, population stratification, technical biases, insufficient quality control or inappropriate statistical analyses. Replication may, however, be challenging even when the original study describes a true positive association. The reasons include underpowered replication samples, gene × gene, gene × environment interactions, genetic and phenotypic heterogeneity and subjective interpretation of data. In this review, we address classic pitfalls in genetic association studies and provide guidelines for proper discovery and replication genetic association studies with a specific focus on obesity.

  18. Cancer in ANCA-Associated Glomerulonephritis: A Registry-Based Cohort Study

    Directory of Open Access Journals (Sweden)

    Sanjeevan Sriskandarajah

    2017-01-01

    Full Text Available Background. Immunosuppressive therapy for antineutrophil cytoplasmic antibody-associated vasculitis has been associated with increased malignancy risk. Objectives. To quantify the cancer risk associated with contemporary cyclophosphamide-sparing protocols. Methods. Patients from the Norwegian Kidney Biopsy Registry between 1988 and 2012 who had biopsy-verified pauci-immune glomerulonephritis and positive antineutrophil cytoplasmic antibody (ANCA serology were included. Standardised incidence ratios (SIRs were calculated to compare the study cohort with the general population. Results. The study cohort included 419 patients. During 3010 person-years, cancer developed in 41 patients (9.79%; the expected number of cancer cases was 37.5 (8.95%. The cohort had SIRs as follows: 1.09, all cancer types (95% CI, 0.81 to 1.49; 0.96, all types except nonmelanoma skin cancer (95% CI, 0.69 to 1.34; 3.40, nonmelanoma skin cancer (95% CI, 1.62 to 7.14; 3.52, hematologic cancer (95% CI, 1.32 to 9.37; 2.12, posttransplant cancer (95% CI, 1.01 to 4.44; and 1.53, during the 1–5-year follow-up after diagnosis (95% CI, 1.01 to 2.32. Conclusions. Cancer risk did not increase significantly in this cohort with ANCA-associated glomerulonephritis. However, increased risk of nonmelanoma skin cancer, posttransplant cancer, and hematologic cancer indicates an association between immunosuppression and malignancy.

  19. 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.

  20. Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

    Directory of Open Access Journals (Sweden)

    Sandosh Padmanabhan

    2010-10-01

    Full Text Available Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹. The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91], reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027. In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003. In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

  1. Genome-wide association study for milking speed in French Holstein cows

    DEFF Research Database (Denmark)

    Marete, Andrew Gitahi; Sahana, Goutam; Fritz, Sebastian

    2018-01-01

    Using a combination of data from the BovineSNP50 BeadChip SNP array (Illumina, San Diego, CA) and a EuroGenomics (Amsterdam, the Netherlands) custom single nucleotide polymorphism (SNP) chip with SNP pre-selected from whole genome sequence data, we carried out an association study of milking speed...... associated with milking speed. As clinical mastitis and somatic cell score have an unfavorable genetic correlation with milking speed, we tested whether the most significant SNP on these 22 chromosomes associated with milking speed were also associated with clinical mastitis or somatic cell score. Nine...... hundred seventy-one genome-wide significant SNP were associated with milking speed. Of these, 86 were associated with clinical mastitis and 198 with somatic cell score. The most significant association signals for milking speed were observed on chromosomes 7, 8, 10, 14, and 18. The most significant signal...

  2. Genome-Wide Association Study of the Genetic Determinants of Emphysema Distribution.

    Science.gov (United States)

    Boueiz, Adel; Lutz, Sharon M; Cho, Michael H; Hersh, Craig P; Bowler, Russell P; Washko, George R; Halper-Stromberg, Eitan; Bakke, Per; Gulsvik, Amund; Laird, Nan M; Beaty, Terri H; Coxson, Harvey O; Crapo, James D; Silverman, Edwin K; Castaldi, Peter J; DeMeo, Dawn L

    2017-03-15

    Emphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe-predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown. To identify the genetic influences of emphysema distribution in non-alpha-1 antitrypsin-deficient smokers. A total of 11,532 subjects with complete genotype and computed tomography densitometry data in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]; non-Hispanic white and African American), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), and GenKOLS (Genetics of Chronic Obstructive Lung Disease) studies were analyzed. Two computed tomography scan emphysema distribution measures (difference between upper-third and lower-third emphysema; ratio of upper-third to lower-third emphysema) were tested for genetic associations in all study subjects. Separate analyses in each study population were followed by a fixed effect metaanalysis. Single-nucleotide polymorphism-, gene-, and pathway-based approaches were used. In silico functional evaluation was also performed. We identified five loci associated with emphysema distribution at genome-wide significance. These loci included two previously reported associations with COPD susceptibility (4q31 near HHIP and 15q25 near CHRNA5) and three new associations near SOWAHB, TRAPPC9, and KIAA1462. Gene set analysis and in silico functional evaluation revealed pathways and cell types that may potentially contribute to the pathogenesis of emphysema distribution. This multicohort genome-wide association study identified new genomic loci associated with differential emphysematous destruction throughout the lungs. These findings may point to new biologic pathways on which to expand diagnostic and therapeutic

  3. Detecting rare variants in case-parents association studies.

    Directory of Open Access Journals (Sweden)

    Kuang-Fu Cheng

    Full Text Available Despite the success of genome-wide association studies (GWASs in detecting common variants (minor allele frequency ≥0.05 many suggested that rare variants also contribute to the genetic architecture of diseases. Recently, researchers demonstrated that rare variants can show a strong stratification which may not be corrected by using existing methods. In this paper, we focus on a case-parents study and consider methods for testing group-wise association between multiple rare (and common variants in a gene region and a disease. All tests depend on the numbers of transmitted mutant alleles from parents to their diseased children across variants and hence they are robust to the effect of population stratification. We use extensive simulation studies to compare the performance of four competing tests: the largest single-variant transmission disequilibrium test (TDT, multivariable test, combined TDT, and a likelihood ratio test based on a random-effects model. We find that the likelihood ratio test is most powerful in a wide range of settings and there is no negative impact to its power performance when common variants are also included in the analysis. If deleterious and protective variants are simultaneously analyzed, the likelihood ratio test was generally insensitive to the effect directionality, unless the effects are extremely inconsistent in one direction.

  4. [Associated costs with dental studies in a public Mexican university].

    Science.gov (United States)

    Medina-Solís, Carlo Eduardo; Medina-Solís, June Janette; Sánchez-de la Cruz, Alicia; Ascencio-Villagrán, Arturo; de la Rosa-Santillana, Rubén; Mendoza-Rodríguez, Martha; Maupomé, Gerardo

    2014-01-01

    To calculate associated costs with dental studies (ACDS) in a public university. We performed a cross-sectional study using a costing system on a random sample of 376 dental students enrolled at any semester in a public university. To calculate ACDS (Mexican pesos of 2009-1), we used a questionnaire divided into eight sections. Sociodemographic and socioeconomic variables, housing costs, food, transportation, instruments and equipment, as well as remunerations associated with patient care along 16 weeks of classes in each semester were included. We used linear regression. The average of ACDS was of 18,357.54 ± 12,746.81 Mexican pesos. The largest percentage of ACDS (30.2 %) was for clinical instruments (5,537.66 ± 6,260.50). Students also spent funds in paying to patients for their time during care delivered (2,402.11 ± 4,796.50). Associated variables (p 〈 0.001) with the ACDS were having completed at least one clinical course or one theoretical-practical course, living within the state or out of state (compared to students who live in the city where dental studies take place), and being enrolled in the more advanced dental studies. The results indicate that a significant percentage of the cost to students (13.1 %) is related with clinical care delivery.

  5. Impact of associated injuries in the Floating knee: A retrospective study

    Science.gov (United States)

    Rethnam, Ulfin; Yesupalan, Rajam S; Nair, Rajagopalan

    2009-01-01

    Background Floating knee injuries are usually associated with other significant injuries. Do these injuries have implications on the management of the floating knee and the final outcome of patients? Our study aims to assess the implications of associated injuries in the management and final outcome of floating knee. Methods 29 patients with floating knees were assessed in our institution. A retrospective analysis of medical records and radiographs were done and all associated injuries were identified. The impact of associated injuries on delay in initial surgical management, delay in rehabilitation & final outcome of the floating knee were assessed. Results 38 associated injuries were noted. 7 were associated with ipsilateral knee injuries. Lower limb injuries were most commonly associated with the floating knee. Patients with some associated injuries had a delay in surgical management and others a delay in post-operative rehabilitation. Knee ligament and vascular injuries were associated with poor outcome. Conclusion The associated injuries were quite frequent with the floating knee. Some of the associated injuries caused a delay in surgical management and post-operative rehabilitation. In assessment of the final outcome, patients with associated knee and vascular injuries had a poor prognosis. Majority of the patients with associated injuries had a good or excellent outcome. PMID:19144197

  6. The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature

    Directory of Open Access Journals (Sweden)

    Frackelton Edward C

    2010-06-01

    Full Text Available Abstract Background Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies. Methods To examine 51 single nucleotide polymorphisms (SNPs corresponding to the 46 previously reported genomic loci for height in 8,184 European American children with height measurements. We leveraged genotyping data from our ongoing GWA study of height variation in children in order to query the 51 SNPs in this pediatric cohort. Results Sixteen of these SNPs yielded at least nominally significant association to height, representing fifteen different loci including EFEMP1-PNPT1, GPR126, C6orf173, SPAG17, Histone class 1, HLA class III and GDF5-UQCC. Other loci revealed no evidence for association, including HMGA1 and HMGA2. For the 16 associated variants, the genotype score explained 1.64% of the total variation for height z-score. Conclusion Among 46 loci that have been reported to associate with adult height to date, at least 15 also contribute to the determination of height in childhood.

  7. Psychosocial risk factors associated with cyberbullying among adolescents: a population-based study.

    Science.gov (United States)

    Sourander, Andre; Brunstein Klomek, Anat; Ikonen, Maria; Lindroos, Jarna; Luntamo, Terhi; Koskelainen, Merja; Ristkari, Terja; Helenius, Hans

    2010-07-01

    To our knowledge, no population study examining psychosocial and psychiatric risk factors associated with cyberbullying among adolescents exists. To study cross-sectional associations between cyberbullying and psychiatric and psychosomatic problems among adolescents. Population-based cross-sectional study. Finland. The sample consists of 2215 Finnish adolescents aged 13 to 16 years with complete information about cyberbullying and cybervictimization. Self-reports of cyberbullying and cybervictimization during the past 6 months. In the total sample, 4.8% were cybervictims only, 7.4% were cyberbullies only, and 5.4% were cyberbully-victims. Cybervictim-only status was associated with living in a family with other than 2 biological parents, perceived difficulties, emotional and peer problems, headache, recurrent abdominal pain, sleeping difficulties, and not feeling safe at school. Cyberbully-only status was associated with perceived difficulties, hyperactivity, conduct problems, low prosocial behavior, frequent smoking and drunkenness, headache, and not feeling safe at school. Cyberbully-victim status was associated with all of these risk factors. Among cybervictims, being cyberbullied by a same-sex or opposite-sex adult, by an unknown person, and by a group of people were associated with fear for safety, indicating possible trauma. Both cyberbullying and cybervictimization are associated with psychiatric and psychosomatic problems. The most troubled are those who are both cyberbullies and cybervictims. This indicates the need for new strategies for cyberbullying prevention and intervention.

  8. Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting

    NARCIS (Netherlands)

    Slof-Op 't Landt, M. C. T.; Meulenbelt, I.; Bartels, M.; Suchiman, E.; Middeldorp, C. M.; Houwing-Duistermaat, J. J.; van Trier, J.; Onkenhout, E. J.; Vink, J. M.; van Beijsterveldt, C. E. M.; Brandys, M. K.; Sanders, N.; Zipfel, S.; Herzog, W.; Herpertz-Dahlmann, B.; Klampfl, K.; Fleischhaker, C.; Zeeck, A.; de Zwaan, M.; Herpertz, S.; Ehrlich, S.; van Elburg, A. A.; Adan, R. A. H.; Scherag, S.; Hinney, A.; Hebebrand, J.; Boomsma, D. I.; van Furth, E. F.; Slagboom, P. E.

    2011-01-01

    Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of

  9. Association study in eating disorders: TPH2 associates with anorexia nervosa and self induced vomiting

    NARCIS (Netherlands)

    Slof-Op 't Landt, M.C.T.; Meulenbelt, I.; Bartels, M.; Suchiman, E.; Middeldorp, C.M.; Houwing-Duistermaat, J.J.; van Trier, J.; Onkenhout, E.J.; Vink, J.M.; van Beijsterveldt, C.E.M.; Brandys, M.K.; Sanders, N.; Zipfel, S.; Herzog, W.; Herpertz-Dahlmann, B.; Klampfl, K.; Fleischhaker, C.; Zeeck, A.; Zwaan, M.; Herpertz, S.; Ehrlich, S.; van Elburg, A.A.; Adan, R.A.H.; Scherag, S.; Hinney, A.; Hebebrand, J.; Boomsma, D.I.; van Furth, E.F.; Slagboom, P.E.

    2011-01-01

    Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of

  10. Association study in eating disorders : TPH2 associates with anorexia nervosa and self-induced vomiting

    NARCIS (Netherlands)

    't Landt, M. C. T. Slof-Op; Meulenbelt, I.; Bartels, M.; Suchiman, E.; Middeldorp, C. M.; Houwing-Duistermaat, J. J.; van Trier, J.; Onkenhout, E. J.; Vink, J. M.; van Beijsterveldt, C. E. M.; Brandys, M. K.; Sanders, N.; Zipfel, S.; Herpertz-Dahlmann, B.; Klampfl, K.; Fleischhaker, C.; Zeeck, A.; de Zwaan, M.; Herpertz, S.; Ehrlich, S.; van Elburg, A. A.; Adan, R. A. H.; Scherag, S.; Hinney, A.; Hebebrand, J.; Boomsma, D. I.; van Furth, E. F.; Slagboom, P. E.; Herzog, W.

    Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of

  11. Sniffing out significant "Pee values": genome wide association study of asparagus anosmia.

    Science.gov (United States)

    Markt, Sarah C; Nuttall, Elizabeth; Turman, Constance; Sinnott, Jennifer; Rimm, Eric B; Ecsedy, Ethan; Unger, Robert H; Fall, Katja; Finn, Stephen; Jensen, Majken K; Rider, Jennifer R; Kraft, Peter; Mucci, Lorelei A

    2016-12-13

     To determine the inherited factors associated with the ability to smell asparagus metabolites in urine.  Genome wide association study.  Nurses' Health Study and Health Professionals Follow-up Study cohorts.  6909 men and women of European-American descent with available genetic data from genome wide association studies.  Participants were characterized as asparagus smellers if they strongly agreed with the prompt "after eating asparagus, you notice a strong characteristic odor in your urine," and anosmic if otherwise. We calculated per-allele estimates of asparagus anosmia for about nine million single nucleotide polymorphisms using logistic regression. P values asparagus anosmia, all in a region on chromosome 1 (1q44: 248139851-248595299) containing multiple genes in the olfactory receptor 2 (OR2) family. Conditional analyses revealed three independent markers associated with asparagus anosmia: rs13373863, rs71538191, and rs6689553.  A large proportion of people have asparagus anosmia. Genetic variation near multiple olfactory receptor genes is associated with the ability of an individual to smell the metabolites of asparagus in urine. Future replication studies are necessary before considering targeted therapies to help anosmic people discover what they are missing. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Genome wide association study identifies KCNMA1 contributing to human obesity

    DEFF Research Database (Denmark)

    Jiao, Hong; Arner, Peter; Hoffstedt, Johan

    2011-01-01

    Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population....... Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity....

  13. Sources of heterogeneity in studies of the BMI-mortality association.

    Science.gov (United States)

    Peter, Raphael Simon; Nagel, Gabriele

    2017-06-01

    To date, the amount of heterogeneity among studies of the body mass index-mortality association attributable to differences in the age distribution and length of follow-up has not been quantified. Therefore, we wanted to quantify the amount of heterogeneity attributable to age and follow-up in results of studies on the body mass index-mortality relation. We used optima of the body mass index mortality association reported for 30 populations and performed meta-regression to estimate the amount of heterogeneity attributable to sex, ethnicity, mean age at baseline, percentage smokers, and length of follow-up. Ethnicity as single factor accounted for 36% (95% CI, 11-56%) of heterogeneity. Mean age and length of follow-up had an interactive effect and together accounted for 56% (95% CI, 24-74%) of the remaining heterogeneity. Sex did not significantly contribute to the heterogeneity, after controlling for ethnicity, age, and length of follow-up. A considerable amount of heterogeneity in studies of the body mass index-mortality association is attributable to ethnicity, age, and length of follow-up. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  14. 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.

  15. 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.

  16. Genome-Wide Association Study Reveals Novel Genes Associated with Culm Cellulose Content in Bread Wheat (Triticum aestivum, L.

    Directory of Open Access Journals (Sweden)

    Simerjeet Kaur

    2017-11-01

    Full Text Available Plant cell wall formation is a complex, coordinated and developmentally regulated process. Cellulose is the most dominant constituent of plant cell walls. Because of its paracrystalline structure, cellulose is the main determinant of mechanical strength of plant tissues. As the most abundant polysaccharide on earth, it is also the focus of cellulosic biofuel industry. To reduce culm lodging in wheat and for improved ethanol production, delineation of the variation for stem cellulose content could prove useful. We present results on the analysis of the stem cellulose content of 288 diverse wheat accessions and its genome-wide association study (GWAS. Cellulose concentration ranged from 35 to 52% (w/w. Cellulose content was normally distributed in the accessions around a mean and median of 45% (w/w. Genome-wide marker-trait association study using 21,073 SNPs helped identify nine SNPs that were associated (p < 1E-05 with cellulose content. Four strongly associated (p < 8.17E-05 SNP markers were linked to wheat unigenes, which included β-tubulin, Auxin-induced protein 5NG4, and a putative transmembrane protein of unknown function. These genes may be directly or indirectly involved in the formation of cellulose in wheat culms. GWAS results from this study have the potential for genetic manipulation of cellulose content in bread wheat and other small grain cereals to enhance culm strength and improve biofuel production.

  17. Common and Rare Variant Association Study for Plasma Lipids and Coronary Artery Disease.

    Science.gov (United States)

    Tada, Hayato; Kawashiri, Masa-aki; Konno, Tetsuo; Yamagishi, Masakazu; Hayashi, Kenshi

    2016-01-01

    Blood lipid levels are highly heritable and modifiable risk factors for coronary artery disease (CAD), and are the leading cause of death worldwide. These facts have motivated human genetic association studies that have the substantial potential to define the risk factors that are causal and to identify pathways and therapeutic targets for lipids and CAD.The success of the HapMap project that provided an extensive catalog of human genetic variations and the development of microarray based genotyping chips (typically containing variations with allele frequencies > 5%) facilitated common variant association study (CVAS; formerly termed genome-wide association study, GWAS) identifying disease-associated variants in a genome-wide manner. To date, 157 loci associated with blood lipids and 46 loci with CAD have been successfully identified, accounting for approximately 12%-14% of heritability for lipids and 10% of heritability for CAD. However, there is yet a major challenge termed "missing heritability problem," namely the observation that loci detected by CVAS explain only a small fraction of the inferred genetic variations. To explain such missing portions, focuses in genetic association studies have shifted from common to rare variants. However, it is challenging to apply rare variant association study (RVAS) in an unbiased manner because such variants typically lack the sufficient number to be identified statistically.In this review, we provide a current understanding of the genetic architecture mostly derived from CVAS, and several updates on the progress and limitations of RVAS for lipids and CAD.

  18. 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.)

  19. 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.)

  20. Factors associated with voice disorders among teachers: a case-control study.

    Science.gov (United States)

    Giannini, Susana Pimentel Pinto; Latorre, Maria do Rosário Dias de Oliveira; Ferreira, Léslie Piccolotto

    2013-01-01

    We aimed at verifying an association between voice disorders/stress and loss of work ability among female teachers who work in São Paulo's public school system. This is a paired case- control study. The case group was composed offiteachers with alterations in speech and larynges assessments, and the control group was formed by teachers without alterations in these evaluations who work in the same schools. Both groups answered the following questionnaires: Conditions of Vocal Production-Teachers, Job Stress Scale, and Work Ability Index. The analysis was performed using the chi-square association test and logistic regression models with the purpose of estimating the association between independent variables and voice disorders. We found differences between the groups in relation to stress in the workplace under high demand, a situation that poses greater risks of adverse reactions to the workers' physical and mental health. Regarding the ability to work, the categories poor and moderate ability for work are associated with voice disorders, regardless of job stress factors, age, and the unsatisfactory acoustic properties of the classrooms. This study confirmed the association between voice disorders and job stress, as well as between voice disorders and loss of work ability.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  3. Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity.

    Science.gov (United States)

    Gueorguiev, Maria; Lecoeur, Cécile; Meyre, David; Benzinou, Michael; Mein, Charles A; Hinney, Anke; Vatin, Vincent; Weill, Jacques; Heude, Barbara; Hebebrand, Johannes; Grossman, Ashley B; Korbonits, Márta; Froguel, Philippe

    2009-04-01

    Ghrelin exerts a stimulatory effect on appetite and regulates energy homeostasis. Ghrelin gene variants have been shown to be associated with metabolic traits, although there is evidence suggesting linkage and association with obesity and the ghrelin receptor (GHSR). We hypothesized that these genes are good candidates for susceptibility to obesity. Direct sequencing identified 12 ghrelin single-nucleotide polymorphisms (SNPs) and 8 GHSR SNPs. The 10 common SNPs were genotyped in 1,275 obese subjects and in 1,059 subjects from a general population cohort of European origin. In the obesity case-control study, the GHSR SNP rs572169 was found to be associated with obesity (P = 0.007 in additive model, P = 0.001 in dominant model, odds ratio (OR) 1.73, 95% confidence interval (1.23-2.44)). The ghrelin variant, g.A265T (rs4684677), showed an association with obesity (P = 0.009, BMI adjusted for age and sex) in obese families. The ghrelin variant, g.A-604G (rs27647), showed an association with insulin levels at 2-h post-oral glucose tolerance test (OGTT) (P = 0.009) in obese families. We found an association between the eating behavior "overeating" and the GHSR SNP rs2232169 (P = 0.02) in obese subjects. However, none of these associations remained significant when corrected for multiple comparisons. Replication of the nominal associations with obesity could not be confirmed in a German genome-wide association (GWA) study for rs4684677 and rs572169 polymorphisms. Our data suggest that common polymorphisms in ghrelin and its receptor genes are not major contributors to the development of polygenic obesity, although common variants may alter body weight and eating behavior and contribute to insulin resistance, in particular in the context of early-onset obesity.

  4. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study.

    Science.gov (United States)

    Dehghan, Abbas; Köttgen, Anna; Yang, Qiong; Hwang, Shih-Jen; Kao, Wh Linda; Rivadeneira, Fernando; Boerwinkle, Eric; Levy, Daniel; Hofman, Albert; Astor, Brad C; Benjamin, Emelia J; van Duijn, Cornelia M; Witteman, Jacqueline C; Coresh, Josef; Fox, Caroline S

    2008-12-06

    Hyperuricaemia, a highly heritable trait, is a key risk factor for gout. We aimed to identify novel genes associated with serum uric acid concentration and gout. Genome-wide association studies were done for serum uric acid in 7699 participants in the Framingham cohort and in 4148 participants in the Rotterdam cohort. Genome-wide significant single nucleotide polymorphisms (SNPs) were replicated in white (n=11 024) and black (n=3843) individuals who took part in the study of Atherosclerosis Risk in Communities (ARIC). The SNPs that reached genome-wide significant association with uric acid in either the Framingham cohort (pgout. The results obtained in white participants were combined using meta-analysis. Three loci in the Framingham cohort and two in the Rotterdam cohort showed genome-wide association with uric acid. Top SNPs in each locus were: missense rs16890979 in SLC2A9 (p=7.0 x 10(-168) and 2.9 x 10(-18) for white and black participants, respectively); missense rs2231142 in ABCG2 (p=2.5 x 10(-60) and 9.8 x 10(-4)), and rs1165205 in SLC17A3 (p=3.3 x 10(-26) and 0.33). All SNPs were direction-consistent with gout in white participants: rs16890979 (OR 0.59 per T allele, 95% CI 0.52-0.68, p=7.0 x 10(-14)), rs2231142 (1.74, 1.51-1.99, p=3.3 x 10(-15)), and rs1165205 (0.85, 0.77-0.94, p=0.002). In black participants of the ARIC study, rs2231142 was direction-consistent with gout (1.71, 1.06-2.77, p=0.028). An additive genetic risk score of high-risk alleles at the three loci showed graded associations with uric acid (272-351 mumol/L in the Framingham cohort, 269-386 mumol/L in the Rotterdam cohort, and 303-426 mumol/L in white participants of the ARIC study) and gout (frequency 2-13% in the Framingham cohort, 2-8% in the Rotterdam cohort, and 1-18% in white participants in the ARIC study). We identified three genetic loci associated with uric acid concentration and gout. A score based on genes with a putative role in renal urate handling showed a substantial risk

  5. Genome-wide association study of smoking behaviors in COPD patients

    Science.gov (United States)

    Siedlinski, Mateusz; Cho, Michael H.; Bakke, Per; Gulsvik, Amund; Lomas, David A.; Anderson, Wayne; Kong, Xiangyang; Rennard, Stephen I.; Beaty, Terri H.; Hokanson, John E.; Crapo, James D.; Silverman, Edwin K.

    2012-01-01

    Background Cigarette smoking is a major risk factor for COPD and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a Dopamine Beta-Hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in COPD subjects. Methods GWAS were conducted in 4 independent cohorts encompassing 3,441 ever-smoking COPD subjects (GOLD stage II or higher). Untyped SNPs were imputed using HapMap (phase II) panel. Results from all cohorts were meta-analyzed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10−7. No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10−6. Nominally significant associations with candidate SNPs within alpha-nicotinic acetylcholine receptors 3/5 (CHRNA3/CHRNA5; e.g. p=0.00011 for SNP rs1051730) and Cytochrome P450 2A6 (CYP2A6; e.g. p=2.78×10−5 for a nonsynonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in the DBH was significantly (p=0.015) associated with smoking cessation. Conclusion We identified two candidate regions associated with age at smoking initiation in COPD subjects. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviors of COPD patients. PMID:21685187

  6. Association of diabetes mellitus and dementia : The Rotterdam study

    NARCIS (Netherlands)

    Ott, A; Stolk, RP; Hofman, A; vanHarskamp, F; Grobbee, DE; Breteler, MMB

    1996-01-01

    Dementia and non-insulin-dependent diabetes mellitus (NIDDM) are highly prevalent disorders in the elderly. Diabetes has repeatedly been reported to affect cognition, but its relation with dementia is uncertain. We therefore studied the association between diabetes and dementia in the Rotterdam

  7. Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies

    Directory of Open Access Journals (Sweden)

    Qiong Yang

    2012-01-01

    Full Text Available Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical or different types of components (e.g., some are continuous and others are categorical. We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.

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

    Science.gov (United States)

    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

  9. 'Smoking genes': a genetic association study.

    Directory of Open Access Journals (Sweden)

    Zoraida Verde

    Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.

  10. 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

  11. 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

  12. Genome-Wide Association Study in Obsessive-Compulsive Disorder: Results from the OCGAS

    Science.gov (United States)

    Mattheisen, Manuel; Samuels, Jack F.; Wang, Ying; Greenberg, Benjamin D.; Fyer, Abby J.; McCracken, James T.; Geller, Daniel A.; Murphy, Dennis L.; Knowles, James A.; Grados, Marco A.; Riddle, Mark A.; Rasmussen, Steven A.; McLaughlin, Nicole C.; Nurmi, Erica; Askland, Kathleen D.; Qin, Hai-De; Cullen, Bernadette A.; Piacentini, John; Pauls, David L.; Bienvenu, O. Joseph; Stewart, S. Evelyn; Liang, Kung-Yee; Goes, Fernando S.; Maher, Brion; Pulver, Ann E.; Shugart, Yin-Yao; Valle, David; Lange, Cristoph; Nestadt, Gerald

    2014-01-01

    Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients, with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1 065 families (containing 1 406 patients with OCD), combined with population-based samples (resulting in a total sample of 5 061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at SNP- and gene-levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13×10−7). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of GWAS signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2, and PTPRD. Analyses at the gene-level revealed association of IQCK and C16orf88 (both P<1×10−6, experiment-wide significant), as well as OFCC1 (P=6.29×10−5). The suggestive findings in this study await replication in larger samples. PMID:24821223

  13. 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

  14. [Mother-newborn relational risk - Study of prevalence and associated variables].

    Science.gov (United States)

    Muñoz, Maribel; Poo, Ana María; Baeza, Bernardita; Bustos, M Luis

    2015-01-01

    Clinical evidence reveals the importance of mother-newborn bonding experience for health promoting and maintenance of human life. If the newborn lacks care and affection, she/he may develop an attachment disorder. A predictive scale regarding the risk of mothernewborn relationships is available, which makes possible an early intervention to prevent the development of relational disorders. The aim of this study is to apply the Kimelman measurement scale to determine the relational risk in mother-newborn pairs, as well as the prevalence and the associated biopsychosocial variables. A cross-sectional study with a probabilistic sample of 333 mother-infant pairs in postpartum maternity at Temuco hospital. The Kimelman mother-newborn attachment assessment guide was used. Biopsychosocial variables were obtained from the mothers studied. The association of biopsychosocial variables with relational risk was analyzed using OR and confidence intervals of 95%. The prevalence of high relational risk was 43.8%. The associated biopsychosocial variables included, women with no steady partner, single parent, teenage mothers, unwanted and unplanned pregnancy. Almost half of the mothers were in the high risk group. Early identification of relational risk and its related variables could help in the intervention in this vulnerable group. Copyright © 2015. Publicado por Elsevier España, S.L.U.

  15. 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.

  16. Association Between Anemia and Cerebral Venous Thrombosis: Case-Control Study

    NARCIS (Netherlands)

    Coutinho, Jonathan M.; Zuurbier, Susanna M.; Gaartman, Aafke E.; Dikstaal, Arienne A.; Stam, Jan; Middeldorp, Saskia; Cannegieter, Suzanne C.

    2015-01-01

    Anemia is often considered to be a risk factor for cerebral venous thrombosis (CVT), but this assumption is mostly based on case reports. We investigated the association between anemia and CVT in a controlled study. Unmatched case-control study: cases were adult patients with CVT included in a

  17. Characteristics Associated with Hallux Valgus in a Population-Based Study of Older Adults: The Framingham Foot Study

    Science.gov (United States)

    Dufour, Alyssa B.; Casey, Virginia A.; Golightly, Yvonne M.; Hannan, Marian T.

    2015-01-01

    Objective Hallux valgus (HV) is common in older adults, but limited studies of risk factors have reported conflicting results. This cross-sectional analysis examined the association of HV with foot pain and other characteristics in older adults. Methods HV, foot pain, foot structure (planus, rectus, cavus), current and past high heel use, age, and body mass index were assessed in the population-based Framingham Foot Study. Sex-specific logistic and multinomial logistic regression examined the association of HV and HV with pain with study variables. Results Of 1352 men and 1725 women (mean age 66 ± 10.5 years), 22% of men and 44% of women had HV and 3% of men and 11% of women had HV with pain. Foot pain increased odds of HV in both sexes (p 30 kg/m2 decreased odds of HV by 33% in men and 45% in women (p<0.05). In women only, odds of Pain & HV vs. No Pain & No HV were greater with older age and planus foot structure. Conclusions Our work showed different associations in participants who had HV with pain compared to those without foot pain. In both men and women, strong relations were observed between HV and foot pain and inversely with BMI. Older age was associated with HV in women only, as were protective associations with cavus foot structure. PMID:24965070

  18. Associations of Coffee Drinking and Cancer Mortality in the Cancer Prevention Study-II.

    Science.gov (United States)

    Gapstur, Susan M; Anderson, Rebecca L; Campbell, Peter T; Jacobs, Eric J; Hartman, Terryl J; Hildebrand, Janet S; Wang, Ying; McCullough, Marjorie L

    2017-10-01

    Background: Associations of coffee consumption with cancer mortality are inconsistent for many types of cancer, and confounding by smoking is an important concern. Methods: Cox proportional hazards regression was used to estimate multivariable-adjusted HRs for coffee consumption associated with death from all cancers combined and from specific cancer types among 922,896 Cancer Prevention Study-II participants ages 28-94 years who completed a four-page questionnaire and were cancer free at baseline in 1982. Results: During follow-up through 2012, there were 118,738 cancer-related deaths. There was a nonlinear association between coffee consumption and all-cancer death among current smokers and former smokers and no association among never smokers. Among nonsmokers, a 2 cup/day increase in coffee consumption was inversely associated with death from colorectal [HR = 0.97; 95% confidence interval (CI) 0.95-0.99], liver [HR = 0.92; 95% CI, 0.88-0.96], and female breast (HR = 0.97; 95% CI, 0.94-0.99) cancers, and positively associated with esophageal cancer-related death (HR = 1.07; 95% CI, 1.02-1.12). For head and neck cancer, a nonlinear inverse association was observed starting at 2-3 cups per day (HR = 0.72; 95% CI, 0.55-0.95), with similar associations observed at higher levels of consumption. Conclusions: These findings are consistent with many other studies that suggest coffee drinking is associated with a lower risk of colorectal, liver, female breast, and head and neck cancer. The association of coffee consumption with higher risk of esophageal cancer among nonsmokers in our study should be confirmed. Impact: These results underscore the importance of assessing associations between coffee consumption and cancer mortality by smoking status. Cancer Epidemiol Biomarkers Prev; 26(10); 1477-86. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. 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.

  20. [Immigration and factors associated with breastfeeding. CALINA study].

    Science.gov (United States)

    Oves Suárez, B; Escartín Madurga, L; Samper Villagrasa, M P; Cuadrón Andrés, L; Alvarez Sauras, M L; Lasarte Velillas, J J; Moreno Aznar, L A; Rodríguez Martínez, G

    2014-07-01

    To identify socio-cultural, obstetric and perinatal characteristics associated with complete breastfeeding (CBF) during the first 4 months of age, depending on maternal origin. Socio-cultural, obstetric and perinatal aspects associated with breastfeeding depending on maternal origin were evaluated in a longitudinal study in a representative infant population from Aragon (n = 1452). The prevalence of CBF was higher in immigrant mothers than in those from Spain. CBF was maintained in 37.2% of mothers from Spain at 4 months, compared with 43% of immigrants (P=.039) (RR Spanish/immigrants=0.76; 95% CI: 0.58-0.99); at 6 months this occurred in 13.9% vs. 23.8%, respectively (P<.001) (RR Spanish/immigrants=0.52; 95% CI: 0.37-0.72). The factors associated with CBF at 4 months are different between both groups. Mothers born in Spain are older (P=.002), have higher academic level (P=.001), greater parity (P=.003), and a higher probability of vaginal delivery (P=.005); and their children have the highest anthropometric values at birth. However, in immigrant mothers, the maintenance of CBF was associated with a higher maternal body mass index and with working at home. In both groups, CBF remains more frequently in those mothers who do not smoke (P=.001). The prevalence of CBF during the first months of life is higher in immigrant mothers than in those from Spain, and socio-cultural, obstetric and perinatal factors are different, depending on maternal origin. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  1. Evaluation of seven common lipid associated loci in a large Indian sib pair study.

    Science.gov (United States)

    Rafiq, Sajjad; Venkata, Kranthi Kumar M; Gupta, Vipin; Vinay, D G; Spurgeon, Charles J; Parameshwaran, Smitha; Madana, Sandeep N; Kinra, Sanjay; Bowen, Liza; Timpson, Nicholas J; Smith, George Davey; Dudbridge, Frank; Prabhakaran, Dorairaj; Ben-Shlomo, Yoav; Reddy, K Srinath; Ebrahim, Shah; Chandak, Giriraj R

    2012-11-14

    Genome wide association studies (GWAS), mostly in Europeans have identified several common variants as associated with key lipid traits. Replication of these genetic effects in South Asian populations is important since it would suggest wider relevance for these findings. Given the rising prevalence of metabolic disorders and heart disease in the Indian sub-continent, these studies could be of future clinical relevance. We studied seven common variants associated with a variety of lipid traits in previous GWASs. The study sample comprised of 3178 sib-pairs recruited as participants for the Indian Migration Study (IMS). Associations with various lipid parameters and quantitative traits were analyzed using the Fulker genetic association model. We replicated five of the 7 main effect associations with p-values ranging from 0.03 to 1.97x10(-7). We identified particularly strong association signals at rs662799 in APOA5 (beta=0.18 s.d, p=1.97 x 10(-7)), rs10503669 in LPL (beta =-0.18 s.d, p=1.0 x 10(-4)) and rs780094 in GCKR (beta=0.11 s.d, p=0.001) loci in relation to triglycerides. In addition, the GCKR variant was also associated with total cholesterol (beta=0.11 s.d, p=3.9x10(-4)). We also replicated the association of rs562338 in APOB (p=0.03) and rs4775041 in LIPC (p=0.007) with LDL-cholesterol and HDL-cholesterol respectively. We report associations of five loci with various lipid traits with the effect size consistent with the same reported in Europeans. These results indicate an overlap of genetic effects pertaining to lipid traits across the European and Indian populations.

  2. 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.

  3. permGPU: Using graphics processing units in RNA microarray association studies

    Directory of Open Access Journals (Sweden)

    George Stephen L

    2010-06-01

    Full Text Available Abstract Background Many analyses of microarray association studies involve permutation, bootstrap resampling and cross-validation, that are ideally formulated as embarrassingly parallel computing problems. Given that these analyses are computationally intensive, scalable approaches that can take advantage of multi-core processor systems need to be developed. Results We have developed a CUDA based implementation, permGPU, that employs graphics processing units in microarray association studies. We illustrate the performance and applicability of permGPU within the context of permutation resampling for a number of test statistics. An extensive simulation study demonstrates a dramatic increase in performance when using permGPU on an NVIDIA GTX 280 card compared to an optimized C/C++ solution running on a conventional Linux server. Conclusions permGPU is available as an open-source stand-alone application and as an extension package for the R statistical environment. It provides a dramatic increase in performance for permutation resampling analysis in the context of microarray association studies. The current version offers six test statistics for carrying out permutation resampling analyses for binary, quantitative and censored time-to-event traits.

  4. Sniffing out significant “Pee values”: genome wide association study of asparagus anosmia

    Science.gov (United States)

    Markt, Sarah C; Nuttall, Elizabeth; Turman, Constance; Sinnott, Jennifer; Rimm, Eric B; Ecsedy, Ethan; Unger, Robert H; Fall, Katja; Finn, Stephen; Jensen, Majken K; Rider, Jennifer R; Kraft, Peter

    2016-01-01

    Objective To determine the inherited factors associated with the ability to smell asparagus metabolites in urine. Design Genome wide association study. Setting Nurses’ Health Study and Health Professionals Follow-up Study cohorts. Participants 6909 men and women of European-American descent with available genetic data from genome wide association studies. Main outcome measure Participants were characterized as asparagus smellers if they strongly agreed with the prompt “after eating asparagus, you notice a strong characteristic odor in your urine,” and anosmic if otherwise. We calculated per-allele estimates of asparagus anosmia for about nine million single nucleotide polymorphisms using logistic regression. P values asparagus anosmia, all in a region on chromosome 1 (1q44: 248139851-248595299) containing multiple genes in the olfactory receptor 2 (OR2) family. Conditional analyses revealed three independent markers associated with asparagus anosmia: rs13373863, rs71538191, and rs6689553. Conclusion A large proportion of people have asparagus anosmia. Genetic variation near multiple olfactory receptor genes is associated with the ability of an individual to smell the metabolites of asparagus in urine. Future replication studies are necessary before considering targeted therapies to help anosmic people discover what they are missing. PMID:27965198

  5. The association between intelligence and telomere length: a longitudinal population based study.

    Directory of Open Access Journals (Sweden)

    Eva M Kingma

    Full Text Available Low intelligence has been associated with poor health and mortality, but underlying mechanisms remain obscure. We hypothesized that low intelligence is associated with accelerated biological ageing as reflected by telomere length; we suggested potential mediation of this association by unhealthy behaviors and low socioeconomic position. The study was performed in a longitudinal population-based cohort study of 895 participants (46.8% males. Intelligence was measured with the Generalized Aptitude-Test Battery at mean age 52.8 years (33-79 years, SD=11.3. Leukocyte telomere length was measured by PCR. Lifestyle and socioeconomic factors were assessed using written self-report measures. Linear regression analyses, adjusted for age, sex, and telomere length measured at the first assessment wave (T1, showed that low intelligence was associated with shorter leukocyte telomere length at approximately 2 years follow-up (beta= .081, t=2.160, p= .031. Nearly 40% of this association was explained by an unhealthy lifestyle, while low socioeconomic position did not add any significant mediation. Low intelligence may be a risk factor for accelerated biological ageing, thereby providing an explanation for its association with poor health and mortality.

  6. Genome-wide association study of the four-constitution medicine.

    Science.gov (United States)

    Yin, Chang Shik; Park, Hi Joon; Chung, Joo-Ho; Lee, Hye-Jung; Lee, Byung-Cheol

    2009-12-01

    Four-constitution medicine (FCM), also known as Sasang constitutional medicine, and the heritage of the long history of individualized acupuncture medicine tradition, is one of the holistic and traditional systems of constitution to appraise and categorize individual differences into four major types. This study first reports a genome-wide association study on FCM, to explore the genetic basis of FCM and facilitate the integration of FCM with conventional individual differences research. Healthy individuals of the Korean population were classified into the four constitutional types (FCTs). A total of 353,202 single nucleotide polymorphisms (SNPs) were typed using whole genome amplified samples, and six-way comparison of FCM types provided lists of significantly differential SNPs. In one-to-one FCT comparisons, 15,944 SNPs were significantly differential, and 5 SNPs were commonly significant in all of the three comparisons. In one-to-two FCT comparisons, 22,616 SNPs were significantly differential, and 20 SNPs were commonly significant in all of the three comparison groups. This study presents the association between genome-wide SNP profiles and the categorization of the FCM, and it could further provide a starting point of genome-based identification and research of the constitutions of FCM.

  7. Molecular evaluation of genetic diversity and association studies in ...

    Indian Academy of Sciences (India)

    Molecular evaluation of genetic diversity and association studies in rice. (Oryza sativa L.) C. Vanniarajan, K. K. Vinod and Andy Pereira. J. Genet. 91, 9–19. Table 1. Chromosome-wise distribution of SSR alleles and their number (k), polymorphic information content (PIC) and allele discrimination index (Dm). Chromosome.

  8. Association between erectile dysfunction and chronic periodontitis: a clinical study.

    Science.gov (United States)

    Uppal, Ranjit Singh; Bhandari, Rajat; Singh, Karanparkash

    2014-01-01

    In recent years, evidence has come forth supporting the notion that localized infectious diseases such as periodontal disease may indeed influence a number of systemic diseases. Erectile dysfunction (ED) and chronic periodontitis have common risk factors such as diabetes mellitus, cardiac diseases and smoking etc. The aim was to evaluate the periodontal status of the subjects suffering from ED and to find association between vasculogenic ED and chronic periodontitis, if any. A total of 53 subjects suffering from vasculogenic ED were enrolled for the study and were divided into three groups on the basis of severity of ED. The clinical (probing pocket depth) and radiographic parameters (alveolar bone loss) were recorded and periodontal status of three groups was evaluated, compared and an attempt was made to find an association between ED and chronic periodontitis. Karl Pearson's correlation was used to assess an association between the two conditions. One-way ANOVA and Scheffe's test were used to find the significant difference of chronic periodontitis with severity of ED. Karl Pearson's correlation was used to find an association between chronic periodontitis and ED. Statistically significant mean differences of 1.73 mm, 0.56 mm and 1.17 mm were recorded when comparison was made among Group I and III, Group I and II and Group II and III, respectively. Mean differences in bone loss among three groups were also statistically significant. Both the diseases were positively correlated to each other. 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.

  9. Savannah River Site: Canyons and associated facilities utilization study

    International Nuclear Information System (INIS)

    Ellison, D.; Dickenson, J.

    1995-01-01

    The Westinghouse Savannah River Company was asked by the U.S. Department of Energy (DOE) to study options for utilization of Savannah River Site (SRS) Canyons and Associated Facilities to support existing and potential future material stabilization and/or disposition missions. This report is WSRC's response to that request. It includes: (1) A compilation of pending DOE material stabilization and/or disposition decisions involving utilization of SRS canyons and associated facilities, including discussion of quantities and expected availability of materials for which SRS handling and/or processing capability is a reasonable alternative under consideration. (2) A description of SRS canyons and associated facilities affected by pending DOE material stabilization and/or disposition decisions, including discussion of material handling and/or processing capabilities and capacities. (3) A comparative evaluation of three proposed scenarios for SRS canyon utilization with respect to startup and operating schedules; annual and life cycle costs; impacts on completion of commitments in the DOE Implementation Plan (IP) for Defense Nuclear Facilities Safety Board (DNFSB) Recommendation 94-1; SRS ability to support alternatives under consideration in pending DOE materials stabilization and/or disposition decisions; and timing for potential transition to deactivation. (4) The sensitivity of the comparative evaluation of the three canyon utilization scenarios to the effect of the selection of other alternatives for individual stabilization missions or individual new missions. Briefings on the scope of this study have been presented to key representatives of several SRS public stakeholder groups. Briefings on the major conclusions from this study have been presented to WSRC Management, DOE-SR, EM-60, EM-1, and the DNFSB

  10. Anterior cervical spine surgery-associated complications in a retrospective case-control study

    OpenAIRE

    Tasiou, Anastasia; Giannis, Theofanis; Brotis, Alexandros G.; Siasios, Ioannis; Georgiadis, Iordanis; Gatos, Haralampos; Tsianaka, Eleni; Vagkopoulos, Konstantinos; Paterakis, Konstantinos; Fountas, Kostas N.

    2017-01-01

    Anterior cervical spine procedures have been associated with satisfactory outcomes. However, the occurrence of troublesome complications, although uncommon, needs to be taken into consideration. The purpose of our study was to assess the actual incidence of anterior cervical spine procedure-associated complications and identify any predisposing factors. A total of 114 patients undergoing anterior cervical procedures over a 6-year period were included in our retrospective, case-control study. ...

  11. Association between bullous pemphigoid and neurologic diseases: a case-control study.

    Science.gov (United States)

    Casas-de-la-Asunción, E; Ruano-Ruiz, J; Rodríguez-Martín, A M; Vélez García-Nieto, A; Moreno-Giménez, J C

    2014-11-01

    In the past 10 years, bullous pemphigoid has been associated with other comorbidities and neurologic and psychiatric conditions in particular. Case series, small case-control studies, and large population-based studies in different Asian populations, mainland Europe, and the United Kingdom have confirmed this association. However, no data are available for the Spanish population. This was an observational, retrospective, case-control study with 1:2 matching. Fifty-four patients with bullous pemphigoid were selected. We compared the percentage of patients in each group with concurrent neurologic conditions, ischemic heart disease, diabetes, chronic obstructive pulmonary disease, and solid tumors using univariate logistic regression. An association model was constructed with conditional multiple logistic regression. The case group had a significantly higher percentage of patients with cerebrovascular accident and/or transient ischemic attack (odds ratio [OR], 3.06; 95% CI, 1.19-7.87], dementia (OR, 5.52; 95% CI, 2.19-13.93), and Parkinson disease (OR, 5; 95% CI, 1.57-15.94). A significantly higher percentage of cases had neurologic conditions (OR, 6.34; 95% CI, 2.89-13.91). Dementia and Parkinson disease were independently associated with bullous pemphigoid in the multivariate analysis. Patients with bullous pemphigoid have a higher frequency of neurologic conditions. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

  12. 16S rRNA gene-based association study identified microbial taxa associated with pork intramuscular fat content in feces and cecum lumen.

    Science.gov (United States)

    Fang, Shaoming; Xiong, Xingwei; Su, Ying; Huang, Lusheng; Chen, Congying

    2017-07-19

    Intramuscular fat (IMF) that deposits among muscle fibers or within muscle cells is an important meat quality trait in pigs. Previous studies observed the effects of dietary nutrients and additives on improving the pork IMF. Gut microbiome plays an important role in host metabolism and energy harvest. Whether gut microbiota exerts effect on IMF remains unknown. In this study, we investigated the microbial community structure of 500 samples from porcine cecum and feces using high-throughput 16S rRNA gene sequencing. We found that phylogenetic composition and potential function capacity of microbiome varied between two types of samples. Bacteria wide association study identified 119 OTUs significantly associated with IMF in the two types of samples (FDR microbiome associated with IMF might be caused by the IMF-associated microbial taxa. This study firstly evaluated the contribution of gut microbiome to porcine IMF content. The results presented a potential capacity for improving IMF through modulating gut microbiota.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    DEFF Research Database (Denmark)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ...

  15. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Bruggeman, Richard; Nolen, Willem A.; Penninx, Brenda W.

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  16. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; de Haan, Lieuwe; Linszen, Don H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  17. Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study.

    Science.gov (United States)

    Hoffmann, Sarah; Harms, Hendrik; Ulm, Lena; Nabavi, Darius G; Mackert, Bruno-Marcel; Schmehl, Ingo; Jungehulsing, Gerhard J; Montaner, Joan; Bustamante, Alejandro; Hermans, Marcella; Hamilton, Frank; Göhler, Jos; Malzahn, Uwe; Malsch, Carolin; Heuschmann, Peter U; Meisel, Christian; Meisel, Andreas

    2017-12-01

    Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

  18. 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

  19. Sociodemographic Moderators of Environment-Physical Activity Associations: Results From the International Prevalence Study.

    Science.gov (United States)

    Perez, Lilian G; Conway, Terry L; Bauman, Adrian; Kerr, Jacqueline; Elder, John P; Arredondo, Elva M; Sallis, James F

    2018-01-01

    Associations between the built environment and physical activity (PA) may vary by sociodemographic factors. However, such evidence from international studies is limited. This study tested the moderating effects of sociodemographic factors on associations between perceived environment and self-reported total PA among adults from the International Prevalence Study. Between 2002 and 2003, adults from 9 countries (N = 10,258) completed surveys assessing total PA (International Physical Activity Questionnaire-short), perceived environment, and sociodemographics (age, gender, and education). Total PA was dichotomized as meeting/not meeting (a) high PA levels and (b) minimum PA guidelines. Logistic models tested environment by sociodemographic interactions (24 total). Education and gender moderated the association between safety from crime and meeting high PA levels (interaction P environment-PA associations. International efforts to improve built environments are needed to promote health-enhancing PA and maintain environmental sustainability.

  20. Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia.

    Science.gov (United States)

    Mansour, Hader A; Talkowski, Michael E; Wood, Joel; Chowdari, Kodavali V; McClain, Lora; Prasad, Konasale; Montrose, Debra; Fagiolini, Andrea; Friedman, Edward S; Allen, Michael H; Bowden, Charles L; Calabrese, Joseph; El-Mallakh, Rif S; Escamilla, Michael; Faraone, Stephen V; Fossey, Mark D; Gyulai, Laszlo; Loftis, Jennifer M; Hauser, Peter; Ketter, Terence A; Marangell, Lauren B; Miklowitz, David J; Nierenberg, Andrew A; Patel, Jayendra; Sachs, Gary S; Sklar, Pamela; Smoller, Jordan W; Laird, Nan; Keshavan, Matcheri; Thase, Michael E; Axelson, David; Birmaher, Boris; Lewis, David; Monk, Tim; Frank, Ellen; Kupfer, David J; Devlin, Bernie; Nimgaonkar, Vishwajit L

    2009-11-01

    Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.

  1. Infrared study of new star cluster candidates associated to dusty globules

    Science.gov (United States)

    Soto King, P.; Barbá, R.; Roman-Lopes, A.; Jaque, M.; Firpo, V.; Nilo, J. L.; Soto, M.; Minniti, D.

    2014-10-01

    We present results from a study of a sample of small star clusters associated to dusty globules and bright-rimmed clouds that have been observed under ESO/Chile public infrared survey Vista Variables in the Vía Láctea (VVV). In this short communication, we analyse the near-infrared properties of a set of four small clusters candidates associated to dark clouds. This sample of clusters associated to dusty globules are selected from the new VVV stellar cluster candidates developed by members of La Serena VVV Group (Barbá et al. 2014). Firstly, we are producing color-color and color-magnitude diagrams for both, cluster candidates and surrounding areas for comparison through PSF photometry. The cluster positions are determined from the morphology on the images and also from the comparison of the observed luminosity function for the cluster candidates and the surrounding star fields. Now, we are working in the procedures to establish the full sample of clusters to be analyzed and methods for subtraction of the star field contamination. These clusters associated to dusty globules are simple laboratories to study the star formation relatively free of the influence of large star-forming regions and populous clusters, and they will be compared with those clusters associated to bright-rimmed globules, which are influenced by the energetic action of nearby O and B massive stars.

  2. 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.

  3. Heritability and confirmation of genetic association studies for childhood asthma in twins.

    Science.gov (United States)

    Ullemar, V; Magnusson, P K E; Lundholm, C; Zettergren, A; Melén, E; Lichtenstein, P; Almqvist, C

    2016-02-01

    Although the genetics of asthma has been extensively studied using both quantitative and molecular genetic analysis methods, both approaches lack studies specific to the childhood phenotype and including other allergic diseases. This study aimed to give specific estimates for the heritability of childhood asthma and other allergic diseases, to attempt to replicate findings from genomewide association studies (GWAS) for childhood asthma and to test the same variants against other allergic diseases. In a cohort of 25 306 Swedish twins aged 9 or 12 years, data on asthma were available from parental interviews and population-based registers. The interviews also inquired about wheeze, hay fever, eczema, and food allergy. Through structural equation modeling, the heritability of all phenotypes was calculated. A subset of 10 075 twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from previous GWAS; these were first tested for association with asthma and significant findings also against the other allergic diseases. The heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other allergic diseases, the range was approximately 0.60-0.80. Associations for six SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80, 95% CI 0.74-0.86, P = 1.5*10(-8) ; other significant associations all below P = 3.5*10(-4) ). Of these, only rs3771180 in IL1RL1 was associated with any other allergic disease (for hay fever, OR 0.64, 95% CI 0.53-0.77, P = 2.5*10(-6) ). Asthma and allergic diseases of childhood are highly heritable, and these high-risk genetic variants associated specifically with childhood asthma, except for one SNP shared with hay fever. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Temporomandibular disorders are differentially associated with headache diagnoses: a controlled study.

    Science.gov (United States)

    Gonçalves, Daniela A G; Camparis, Cinara M; Speciali, José G; Franco, Ana L; Castanharo, Sabrina M; Bigal, Marcelo E

    2011-09-01

    Temporomandibular disorders (TMDs) are considered to be comorbid with headaches. Earlier population studies have suggested that TMD may also be a risk factor for migraine progression. If that is true, TMD should be associated with specific headache syndromes (eg, migraine and chronic migraine), but not with headaches overall. Accordingly, our aim was to explore the relationship between TMD subtypes and severity with primary headaches in a controlled clinical study. The sample consisted of 300 individuals. TMDs were assessed using the Research Diagnostic Criteria for TMD, and primary headache was classified according to International Classification for Headache Disorders-2. Univariate and multivariate models assessed headache diagnoses and frequency as a function of the parameters of TMD. Relative to those without TMD, individuals with myofascial TMD were significantly more likely to have chronic daily headaches (CDHs) [relative risk (RR)=7.8; 95% confidence interval (CI), 3.1-19.6], migraine (RR=4.4; 95% CI, 1.7-11.7), and episodic tension-type headache (RR=4.4; 95% CI, 1.5-12.6). Grade of TMD pain was associated with increased odds of CDH (Pheadache (Pheadache frequency. In multivariate analyses, TMD was associated with migraine and CDH (P=0.001). Painful TMD (P=0.0034) and grade of TMD pain (Pheadache frequency. TMD, TMD subtypes, and TMD severity are independently associated with specific headache syndromes and with headache frequency. This differential association suggests that the presence of central facilitation of nociceptive inputs may be of importance, as positive association was observed only when muscular TMD pain was involved.

  5. Association of Facebook Use With Compromised Well-Being: A Longitudinal Study.

    Science.gov (United States)

    Shakya, Holly B; Christakis, Nicholas A

    2017-02-01

    Face-to-face social interactions enhance well-being. With the ubiquity of social media, important questions have arisen about the impact of online social interactions. In the present study, we assessed the associations of both online and offline social networks with several subjective measures of well-being. We used 3 waves (2013, 2014, and 2015) of data from 5,208 subjects in the nationally representative Gallup Panel Social Network Study survey, including social network measures, in combination with objective measures of Facebook use. We investigated the associations of Facebook activity and real-world social network activity with self-reported physical health, self-reported mental health, self-reported life satisfaction, and body mass index. Our results showed that overall, the use of Facebook was negatively associated with well-being. For example, a 1-standard-deviation increase in "likes clicked" (clicking "like" on someone else's content), "links clicked" (clicking a link to another site or article), or "status updates" (updating one's own Facebook status) was associated with a decrease of 5%-8% of a standard deviation in self-reported mental health. These associations were robust to multivariate cross-sectional analyses, as well as to 2-wave prospective analyses. The negative associations of Facebook use were comparable to or greater in magnitude than the positive impact of offline interactions, which suggests a possible tradeoff between offline and online relationships. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Science.gov (United States)

    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

  7. Prioritization of arbitrary faces associated to self: An EEG study.

    Directory of Open Access Journals (Sweden)

    Mateusz Woźniak

    Full Text Available Behavioral and neuroimaging studies have demonstrated that people process preferentially self-related information such as an image of their own face. Furthermore, people rapidly incorporate stimuli into their self-representation even if these stimuli do not have an intrinsic relation to self. In the present study, we investigated the time course of the processes involved in preferential processing of self-related information. In two EEG experiments three unfamiliar faces were identified with verbal labels as either the participant, a friend, or a stranger. Afterwards, participants judged whether two stimuli presented in succession (ISI = 1500ms matched. In experiment 1, faces were followed by verbal labels and in experiment 2, labels were followed by faces. Both experiments showed the same pattern of behavioral and electrophysiological results. If the first stimulus (face or label was associated with self, reaction times were faster and the late frontal positivity following the first stimulus was more pronounced. The self-association of the second stimulus (label or face did not affect response times. However, the central-parietal P3 following presentation of the second stimulus was more pronounced when the second stimulus was preceded by self-related first stimulus. These results indicate that even unfamiliar faces that are associated to self can activate a self-representation. Once the self-representation has been activated the processing of ensuing stimuli is facilitated, irrespective of whether they are associated with the self.

  8. Association between bacterial vaginosis and partner concurrency: a longitudinal study.

    Science.gov (United States)

    Kenyon, Chris R; Buyze, Jozefien; Klebanoff, Mark; Brotman, Rebecca M

    2018-02-01

    The study aimed to test if there was an association between prevalent bacterial vaginosis (BV) and women reporting that their partner had other partners at the same time (partner concurrency). This association has not been assessed in a longitudinal cohort. The Longitudinal Study of Vaginal Flora recruited a cohort of 3620 non-pregnant women aged 15-44 years who presented for routine primary healthcare at 12 clinics in Birmingham, Alabama. Behavioural questionnaires and vaginal smears were obtained quarterly for a year and BV was defined by a Nugent score 7 or higher as well as Amsel criteria. Mixed effects logistic regression was used to assess the relationship between prevalent BV and reporting that one's partner had other partners in the preceding 3-6 months time interval. Nugent score prevalent BV was associated with both reporting that one's partner definitely (adjusted OR (aOR) 1.5; 95% CI 1.2 to 1.8) and possibly (aOR 1.5; 95% CI 1.2 to 1.8) engaged in partner concurrency in the preceding 3-6 months time period. Prevalent BV diagnosed by Amsel criteria was similar. A diagnosis of prevalent BV was associated with reporting that one's partner possibly or definitely engaged in partner concurrency. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Associations between faith, distress and mental adjustment--a Danish survivorship study.

    Science.gov (United States)

    Johannessen-Henry, Christine Tind; Deltour, Isabelle; Bidstrup, Pernille Envold; Dalton, Susanne O; Johansen, Christoffer

    2013-02-01

    Several studies have suggested that religion and spirituality are important for overcoming psychological distress and adjusting mentally to cancer, but these studies did not differentiate between spiritual well-being and specific aspects of faith. We examined the extent to which spiritual well-being, the faith dimension of spiritual well-being and aspects of performed faith are associated with distress and mental adjustment among cancer patients. In a cross-sectional design, 1043 survivors of various cancers filled in a questionnaire on spiritual well-being (FACIT-Sp-12), specific aspects of faith ('belief in a god', 'belief in a god with whom I can talk' and 'experiences of god or a higher power'), religious community and church attendance (DUREL), distress (POMS-SF), adjustment to cancer (Mini-MAC) and sociodemographic factors. Linear regression models were used to analyze the associations between exposure (spiritual well-being and specific faith aspects) and outcome (distress and adjustment to cancer) with adjustment for age, gender, cancer diagnosis and physical and social well-being. Higher spiritual well-being was associated with less total distress (β = -0.79, CI -0.92; -0.66) and increased adjustment to cancer (fighting spirit, anxious preoccupation, helplessness-hopelessness). Specific aspects of faith were associated with high confusion-bewilderment and tension-anxiety, but also lower score on vigor-activity, and with higher anxious-preoccupation, both higher and lower cognitive avoidance, but also more fighting spirit. As hypothesized, spiritual well-being were associated with less distress and better mental adjustment. However, specific aspects of faith were both positively and negatively associated with distress and mental adjustment. The results illustrate the complexity of associations between spiritual well-being and specific aspects of faith with psychological function among cancer survivors.

  10. A Retrospective Study on Magnitude and Factors Associated with ...

    African Journals Online (AJOL)

    Background: Anemia in the postnatal period is a common problem, which has been subject of research recently. Though, it is a common problem, it is a less researched topic in India. Hence, this study was undertaken. Aim: The aim was to know the clinic.social factors associated with anemia in the postpartum period.

  11. Genome–wide association study of carcass weight in commercial Hanwoo cattle

    Science.gov (United States)

    Edea, Zewdu; Jeoung, Yeong Ho; Shin, Sung-Sub; Ku, Jaeul; Seo, Sungbo; Kim, Il-Hoi; Kim, Sang-Wook

    2018-01-01

    Objective The objective of the present study was to validate genes and genomic regions associated with carcass weight using a low-density single nucleotide polymorphism (SNP) Chip in Hanwoo cattle breed. Methods Commercial Hanwoo steers (n = 220) were genotyped with 20K GeneSeek genomic profiler BeadChip. After applying the quality control of criteria of a call rate ≥90% and minor allele frequency (MAF) ≥0.01, a total of 15,235 autosomal SNPs were left for genome-wide association (GWA) analysis. The GWA tests were performed using single-locus mixed linear model. Age at slaughter was fitted as fixed effect and sire included as a covariate. The level of genome-wide significance was set at 3.28×10−6 (0.05/15,235), corresponding to Bonferroni correction for 15,235 multiple independent tests. Results By employing EMMAX approach which is based on a mixed linear model and accounts for population stratification and relatedness, we identified 17 and 16 loci significantly (pcarcass weight for the additive and dominant models, respectively. The second most significant (p = 0.000049) SNP (ARS-BFGL-NGS-28234) on bovine chromosome 4 (BTA4) at 21 Mb had an allele substitution effect of 43.45 kg. Some of the identified regions on BTA2, 6, 14, 22, and 24 were previously reported to be associated with quantitative trait loci for carcass weight in several beef cattle breeds. Conclusion This is the first genome-wide association study using SNP chips on commercial Hanwoo steers, and some of the loci newly identified in this study may help to better DNA markers that determine increased beef production in commercial Hanwoo cattle. Further studies using a larger sample size will allow confirmation of the candidates identified in this study. PMID:29103288

  12. Association between phytosterol intake and colorectal cancer risk: a case-control study.

    Science.gov (United States)

    Huang, Jing; Xu, Ming; Fang, Yu-Jing; Lu, Min-Shan; Pan, Zhi-Zhong; Huang, Wu-Qing; Chen, Yu-Ming; Zhang, Cai-Xia

    2017-03-01

    A study in rodent models showed that phytosterols protected against colon carcinogenesis, probably by inhibiting dysregulated cell cycle progression and inducing cellular apoptosis. However, epidemiological studies on the relationship between phytosterols and colorectal cancer risk are quite limited. The aim of this study was to investigate dietary phytosterol intake in relation to colorectal cancer risk in the Chinese population. A case-control study was conducted from July 2010 to June 2016, recruiting 1802 eligible colorectal cancer cases plus 1813 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. A higher total intake of phytosterols was found to be associated with a 50 % reduction in colorectal cancer risk. After adjusting for various confounders, the OR of the highest quartile intake compared with the lowest quartile intake was 0·50 (95 % CI 0·41, 0·61, P trendphytosterols. An inverse association was also found between the consumption of β-sitosterol, campesterol, campestanol and colorectal cancer risk. However, stigmasterol intake was related to an increased risk of colorectal cancer. No statistically significant association was found between β-sitostanol and colorectal cancer risk. Stratified analysis by sex showed that the positive association of stigmasterol intake with colorectal cancer risk was found only in women. These data indicated that the consumption of total phytosterols, β-sitosterol, campesterol and campestanol is inversely associated with colorectal cancer risk in a Chinese population.

  13. Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits.

    Directory of Open Access Journals (Sweden)

    Tamar Sofer

    Full Text Available Admixture mapping can be used to detect genetic association regions in admixed populations, such as Hispanics/Latinos, by estimating associations between local ancestry allele counts and the trait of interest. We performed admixture mapping of the blood pressure traits systolic and diastolic blood pressure (SBP, DBP, mean arterial pressure (MAP, and pulse pressure (PP, in a dataset of 12,116 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL. Hispanics/Latinos have three predominant ancestral populations (European, African, and Amerindian, for each of which we separately tested local ancestry intervals across the genome. We identified four regions that were significantly associated with a blood pressure trait at the genome-wide admixture mapping level. A 6p21.31 Amerindian ancestry association region has multiple known associations, but none explained the admixture mapping signal. We identified variants that completely explained this signal. One of these variants had p-values of 0.02 (MAP and 0.04 (SBP in replication testing in Pima Indians. A 11q13.4 Amerindian ancestry association region spans a variant that was previously reported (p-value = 0.001 in a targeted association study of Blood Pressure (BP traits and variants in the vitamin D pathway. There was no replication evidence supporting an association in the identified 17q25.3 Amerindian ancestry association region. For a region on 6p12.3, associated with African ancestry, we did not identify any candidate variants driving the association. It may be driven by rare variants. Whole genome sequence data may be necessary to fine map these association signals, which may contribute to disparities in BP traits between diverse populations.

  14. 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

  15. Genome-wide association studies in economics and entrepreneurship research: promises and limitations

    NARCIS (Netherlands)

    Ph.D. Koellinger (Philipp); M.J.H.M. van der Loos (Matthijs); P.J.F. Groenen (Patrick); A.R. Thurik (Roy); F. Rivadeneira Ramirez (Fernando); F.J.A. van Rooij (Frank)

    2010-01-01

    textabstractThe recently developed genome-wide association study (GWAS) design enables the identification of genes specifically associated with economic outcomes such as occupational and other choices. This is a promising new approach for economics research which we aim to apply to the choice for

  16. Multiple comparison procedures for neuroimaging genomewide association studies.

    Science.gov (United States)

    Hua, Wen-Yu; Nichols, Thomas E; Ghosh, Debashis

    2015-01-01

    Recent research in neuroimaging has focused on assessing associations between genetic variants that are measured on a genomewide scale and brain imaging phenotypes. A large number of works in the area apply massively univariate analyses on a genomewide basis to find single nucleotide polymorphisms that influence brain structure. In this paper, we propose using various dimensionality reduction methods on both brain structural MRI scans and genomic data, motivated by the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. We also consider a new multiple testing adjustment method and compare it with two existing false discovery rate (FDR) adjustment methods. The simulation results suggest an increase in power for the proposed method. The real-data analysis suggests that the proposed procedure is able to find associations between genetic variants and brain volume differences that offer potentially new biological insights. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Histone Acetylome-wide Association Study of Autism Spectrum Disorder.

    Science.gov (United States)

    Sun, Wenjie; Poschmann, Jeremie; Cruz-Herrera Del Rosario, Ricardo; Parikshak, Neelroop N; Hajan, Hajira Shreen; Kumar, Vibhor; Ramasamy, Ramalakshmi; Belgard, T Grant; Elanggovan, Bavani; Wong, Chloe Chung Yi; Mill, Jonathan; Geschwind, Daniel H; Prabhakar, Shyam

    2016-11-17

    The association of histone modification changes with autism spectrum disorder (ASD) has not been systematically examined. We conducted a histone acetylome-wide association study (HAWAS) by performing H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) on 257 postmortem samples from ASD and matched control brains. Despite etiological heterogeneity, ≥68% of syndromic and idiopathic ASD cases shared a common acetylome signature at >5,000 cis-regulatory elements in prefrontal and temporal cortex. Similarly, multiple genes associated with rare genetic mutations in ASD showed common "epimutations." Acetylome aberrations in ASD were not attributable to genetic differentiation at cis-SNPs and highlighted genes involved in synaptic transmission, ion transport, epilepsy, behavioral abnormality, chemokinesis, histone deacetylation, and immunity. By correlating histone acetylation with genotype, we discovered >2,000 histone acetylation quantitative trait loci (haQTLs) in human brain regions, including four candidate causal variants for psychiatric diseases. Due to the relative stability of histone modifications postmortem, we anticipate that the HAWAS approach will be applicable to multiple diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Studying risk factors associated with Human Leptospirosis

    Directory of Open Access Journals (Sweden)

    Ramachandra Kamath

    2014-01-01

    Full Text Available Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0, presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02 and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73 and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67 were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still

  19. Association of chronic periodontitis with metabolic syndrome: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Naresh Kumar

    2016-01-01

    Full Text Available Background: Prevalence of metabolic syndrome (MeS is high among Asians, including Indians and is rising, particularly with the adoption of modernized lifestyle. Various studies have reported a significant relationship between periodontal status and MeS. The objective of this study is to investigate the association between periodontitis and MeS. Materials and Methods: The study included 259 subjects (130 cases with chronic periodontitis, 129 controls without chronic periodontitis who underwent medical and periodontal checkup. Five components (obesity, high blood pressure, low- and high-density lipoproteins, cholesterol, hypertriglyceridemia, and high plasma glucose of MeS were evaluated, and individuals with ≥3 positive components were defined as having MeS. The periodontal parameter was clinical attachment level (CAL on the basis of which cases were selected with moderate (CAL loss 3–4 mm and severe (CAL loss ≥5 mm generalized chronic periodontitis. The association between chronic periodontitis and MeS components was investigated using odds ratios (ORs and 95% confidence intervals (CIs. Results: The association of MeS and chronic periodontitis was strong and significant with OR: 2.64, 95% CI: 1.36–5.18, and P< 0.003. Comparison of mean values of components of MeS between cases and controls reveals that the mean waist circumference (mean difference: −4.8 [95% CI: 7.75–−1.84], P< 0.002 and mean triglycerides level (mean difference: −25.75 [95% CI: −49.22–−2.28], P< 0.032 were significantly higher in cases than in control groups. Although mean systolic blood pressure, diastolic blood pressure, and fasting blood sugar level were higher in cases (125.77, 82.99 and 86.38, respectively compared with control (122.81, 81.3 and 83.68, respectively, it was statistically insignificant. Conclusion: The results of this study suggest that there is a strong association between chronic periodontitis and MeS. The association was independent

  20. Burning mouth syndrome and associated factors: A case-control retrospective study.

    Science.gov (United States)

    Chimenos-Küstner, Eduardo; de Luca-Monasterios, Fiorella; Schemel-Suárez, Mayra; Rodríguez de Rivera-Campillo, María E; Pérez-Pérez, Alejandro M; López-López, José

    2017-02-23

    Burning mouth syndrome (BMS) can be defined as burning pain or dysesthesia on the tongue and/or other sites of the oral mucosa without a causative identifiable lesion. The discomfort is usually of daily recurrence, with a higher incidence among people aged 50 to 60 years, affecting mostly the female sex and diminishing their quality of life. The aim of this study was to evaluate the association between several pathogenic factors and burning mouth syndrome. 736 medical records of patients diagnosed of burning mouth syndrome and 132 medical records for the control group were studied retrospectively. The study time span was from January 1990 to December 2014. The protocol included: sex, age, type of oral discomfort and location, among other factors. Analysis of the association between pathogenic factors and BMS diagnosis revealed that only 3 factors showed a statistically significant association: triggers (P=.003), parafunctional habits (P=.006), and oral hygiene (P=.012). There were neither statistically significant differences in BMS incidence between sex groups (P=.408) nor association of BMS with the pathogenic factors of substance abuse (P=.915), systemic pathology (P=.685), and dietary habits (P=.904). Parafunctional habits like bruxism and abnormal movements of tongue and lips can explain the BMS main symptomatology. Psychological aspects and systemic factors should be always considered. As a multifactorial disorder, the treatment of BMS should be executed in a holistic way. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  1. Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia

    Science.gov (United States)

    Mansour, Hader A; Talkowski, Michael E; Wood, Joel; Chowdari, Kodavali V; McClain, Lora; Prasad, Konasale; Montrose, Debra; Fagiolini, Andrea; Friedman, Edward S; Allen, Michael H; Bowden, Charles L; Calabrese, Joseph; El-Mallakh, Rif S; Escamilla, Michael; Faraone, Stephen V; Fossey, Mark D; Gyulai, Laszlo; Loftis, Jennifer M; Hauser, Peter; Ketter, Terence A; Marangell, Lauren B; Miklowitz, David J; Nierenberg, Andrew A; Patel, Jayendra; Sachs, Gary S; Sklar, Pamela; Smoller, Jordan W; Laird, Nan; Keshavan, Matcheri; Thase, Michael E; Axelson, David; Birmaher, Boris; Lewis, David; Monk, Tim; Frank, Ellen; Kupfer, David J; Devlin, Bernie; Nimgaonkar, Vishwajit L

    2012-01-01

    Objective Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods We assayed 276 publicly available ‘tag’ single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results. PMID:19839995

  2. 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.

  3. Case-control genome-wide association study of attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Neale, B.M.; Medland, S.; Ripke, S.; Anney, R.J.; Asherson, P.; Buitelaar, J.K.; Franke, B.; Gill, M.; Kent, L.; Holmans, P.; Middleton, F.; Thapar, A.; Lesch, K.P.; Faraone, S.V.; Daly, M.; Nguyen, T.T.; Schafer, H.; Steinhausen, H.C.; Reif, A.; Renner, T.J.; Romanos, M.; Romanos, J.; Warnke, A.; Walitza, S.; Freitag, C.; Meyer, J.; Palmason, H.; Rothenberger, A.; Hawi, Z.; Sergeant, J.A.; Roeyers, H.; Mick, E.; Biederman, J.

    2010-01-01

    OBJECTIVE: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed.

  4. An epidemiological study of environmental factors associated with canine obesity.

    Science.gov (United States)

    Courcier, E A; Thomson, R M; Mellor, D J; Yam, P S

    2010-07-01

    To assess the relationships between socioeconomic and other environmental factors with canine obesity. This was a cross-sectional questionnaire study of dog owners attending five primary veterinary practices in the UK. Owners were asked about dog age, neuter status, feeding habits, dog exercise, household income and owner age. The body condition score of the dogs was also assessed. Factors hypothesised to be associated with obesity were investigated. In total, data from 696 questionnaires were evaluated. Out of those data evaluated, 35.3% of dogs (n=246) were classed as an ideal body shape, 38.9% (n=271) were overweight, 20.4% (n=142) were obese and 5.3% (n=37) were underweight. Identified risk factors associated with obesity included owner age, hours of weekly exercise, frequency of snacks/treats and personal income. Environmental risk factors associated with canine obesity are multifactorial and include personal income, owner age, frequency of snacks/treats and amount of exercise the dog receives. Awareness about health risks associated with obesity in dogs is significantly less in people in lower income brackets. This phenomenon is recognised in human obesity.

  5. 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.

  6. Genome-wide association study for female fertility in Nordic Red cattle

    DEFF Research Database (Denmark)

    Höglund, Johanna; Buitenhuis, Albert Johannes; Guldbrandtsen, Bernt

    2015-01-01

    cattle. The sub-traits of FTI are: number of inseminations per conception (AIS) in cows (C) and heifers (H), the length in days of the interval from calving to first insemination (ICF) in cows, days from first to last insemination (IFL) in cows and heifers, and 56-day non-return rate (NRR) in cows...... and heifers. The aim of this study was first to identify QTL for FTI by conducting a genome scan for variants associated with fertility index using imputed whole genome sequence data based on 4207 Nordic Red sires, and subsequently analyzing which of the sub-traits were affected by each FTI QTL by associating......). Conclusion This study 1) shows that many markers within FTI QTL regions were significantly associated with both AISH and IFLH, and 2) identified candidate genes for FTI located on BTA6 (GPR125), BTA13 (ANKRD60), BTA15 (GRAMD1B), and BTA24 (ZNF521). It is not known how the genes/variants identified...

  7. Genome-wide Association Study Implicates PARD3B-based AIDS Restriction

    Science.gov (United States)

    Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

    2011-01-01

    Background. Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. Methods.  European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model). Results.  Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 × 10−9) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 × 10−8). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025). Conclusions. These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression. PMID:21502085

  8. Association between adolescent suicide and sociodemographic factors in Chile: cross-sectional ecological study.

    Science.gov (United States)

    Cuadrado, Cristóbal; Zitko, Pedro; Covarrubias, Trinidad; Hernandez, Dunia; Sade, Cristina; Klein, Carolina; Gomez, Alejandro

    2015-01-01

    Adolescent suicide rates (ASR) are a matter of concern worldwide. Causes of this trend are not understood and could correspond to socioeconomic factors such as inequality. To investigate sociodemographic variables related to ASR, particularly the potential association with indicators of socioeconomic inequality. Cross-sectional ecological study analyzing data from 29 health districts with univariate and multivariable multilevel Poisson models. ASR were higher in male adolescents and at increasing age. No association was found between ASR and inequality (Gini coefficient and 20/20 ratio). Analysis revealed that living in a single-parent family is associated with ASR. The usual demographic patterns of adolescent suicide apply in Chile. An emerging variable of interest is single-parent family. No cross-sectional association between social inequality and ASR was found based on conflicting evidence. These results should be explored in future prospective population studies to further understand associated social factors.

  9. 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.

  10. Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

    DEFF Research Database (Denmark)

    Fatemifar, Ghazaleh; Hoggart, Clive J; Paternoster, Lavinia

    2013-01-01

    Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of 'age at first tooth' and 'number of teeth......' using 5998 and 6609 individuals, respectively, from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2 446 724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex...

  11. Association Between Screen-Detected Gallstone Disease and Cancer in a Cohort Study

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted; Sørensen, Lars Tue; Jørgensen, Torben

    2017-01-01

    , sigmoid colon, and rectal cancers were not associated with gallstone disease. Breast cancer had a weak association with gallstone disease depending on other factors (10.6% of patients with gallstone disease vs 7.41% without; hazard ratio, 1.44; 95% confidence interval, 0.99-2.11). Pooled...... ratio, 1.50; 95% confidence interval, 1.12-2.01). Right-side colon cancer was also associated with gallstone disease (2.57% of patients with gallstone disease vs 0.96% without; hazard ratio, 2.04; 95% confidence interval, 1.10-3.78). Pancreatic, esophageal, gastric, pooled colorectal, left-side colon...... nongastrointestinal and prostate cancers were not associated with gallstone disease. Conclusions: Screen-detected gallstone disease in the general population is associated with pooled gastrointestinal and right-side colon cancers. These associations are not due to detection bias or cholecystectomy. Further studies...

  12. 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...

  13. Age-specific association of migraine with cryptogenic TIA and stroke: Population-based study.

    Science.gov (United States)

    Li, Linxin; Schulz, Ursula G; Kuker, Wilhelm; Rothwell, Peter M

    2015-10-27

    To determine whether there is an association between previous migraine and cryptogenic TIA or ischemic stroke at older ages. We determined the age-specific associations of history of migraine and Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtype of TIA and ischemic stroke in a population-based cohort study (Oxford Vascular Study; 2002-2012). Among 1,810 eligible patients with TIA or ischemic stroke, 668 (36.9%) had cryptogenic events, of whom 187 (28.0%) had previous migraine. Migraine was more commonly associated with cryptogenic events than with those of known etiology (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.38-2.16, p TIA or stratified by sex or vascular territory of event. In this population-based study of stroke etiology stratified by age, migraine was most strongly associated with cryptogenic TIA and ischemic stroke, particularly at older ages, suggesting a causal role or a shared etiology. © 2015 American Academy of Neurology.

  14. Associations of Bar and Restaurant Smoking Bans With Smoking Behavior in the CARDIA Study: A 25-Year Study.

    Science.gov (United States)

    Mayne, Stephanie L; Auchincloss, Amy H; Tabb, Loni Philip; Stehr, Mark; Shikany, James M; Schreiner, Pamela J; Widome, Rachel; Gordon-Larsen, Penny

    2018-06-01

    Indoor smoking bans have often been associated with reductions in smoking prevalence. However, few studies have evaluated their association with within-person changes in smoking behaviors. We linked longitudinal data from 5,105 adults aged 18-30 years at baseline from the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1985-2011) to state, county, and local policies mandating 100% smoke-free bars and restaurants by census tract. We used fixed-effects models to examine the association of smoking bans with within-person change in current smoking risk, smoking intensity (smoking ≥10 cigarettes/day on average vs. <10 cigarettes/day), and quitting attempts, using both linear and nonlinear adjustment for secular trends. In models assuming a linear secular trend, smoking bans were associated with a decline in current smoking risk and smoking intensity and an increased likelihood of a quitting attempt. The association with current smoking was greatest among participants with a bachelor's degree or higher. In models with a nonlinear secular trend, pooled results were attenuated (confidence intervals included the null), but effect modification results were largely unchanged. Findings suggest that smoking ban associations may be difficult to disentangle from other tobacco control interventions and emphasize the importance of evaluating equity throughout policy implementation.

  15. The Association of Parental/Caregiver Chronic Stress with Youth Obesity: Findings from the Study of Latino Youth and the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.

    Science.gov (United States)

    Isasi, Carmen R; Hua, Simin; Jung, Molly; Carnethon, Mercedes R; Perreira, Krista; Vidot, Denise C; Salazar, Christian R; McCurley, Jessica L; Sotres-Alvarez, Daniela; Van Horn, Linda; Delamater, Alan M; Llabre, Maria M; Gallo, Linda C

    2017-08-01

    Prior studies indicate that chronic stress is associated with obesity in adults. However, whether parental/caregiver stress is associated with obesity in their offspring has not been widely examined in Hispanic/Latino populations. In this study, we evaluated the role of caregiver chronic stress on child obesity and whether home food environment or child lifestyle behaviors explained the association. The study included a sample of Hispanic/Latino youth and their caregivers (n = 473) from the Study of Latinos (SOL) Youth study and the Hispanic Community Health Study/SOL Sociocultural Study, which enrolled children aged 8-16 years from four cities (Bronx, Chicago, Miami, and San Diego), and provided assessments of adult chronic stress. Poisson regression models were used to assess the association between parental/caregiver stress and child obesity, adjusting for potential confounders. Twenty-two percent of caregivers did not report any chronic stressors, 48% reported 1-2, and 29% reported ≥3 stressors. The prevalence of obesity in youth increased with number of caregiver stressors from 23% among those without caregiver stressors to 35% among those with ≥3 stressors (p for trend 0.03). After model adjustment, youths whose caregivers reported ≥3 stressors were more likely to be obese than youths whose caregivers reported no stressors (prevalence ratio = 1.53; 95% confidence interval 1.01-2.32). This association was independent of food home environment, child diet quality, and child physical activity, but it was not independent of caregiver obesity. These findings suggest that parental/caregiver chronic stress is related to obesity in their children. Future research is needed to confirm this association in longitudinal studies and in other population groups.

  16. A Case–control and a family-based association study revealing an association between CYP2E1 polymorphisms and nasopharyngeal carcinoma risk in Cantonese

    Science.gov (United States)

    Jia, Wei-Hua; Pan, Qing-Hua; Qin, Hai-De; Xu, Ya-Fei; Shen, Guo-Ping; Chen, Lina; Chen, Li-Zhen; Feng, Qi-Sheng; Hong, Ming-Huang; Zeng, Yi-Xin; Shugart, Yin Yao

    2009-01-01

    Nasopharyngeal carcinoma (NPC) is rare in most parts of the world but is more prevalent in Southern China, especially in Guangdong. The cytochrome P450 2E1 (CYP2E1) has been recognized as one of the critically important enzymes involved in oxidizing carcinogens and is probably to be associated with NPC carcinogenesis. To systematically investigate the association between genetic variants in CYP2E1 and NPC risk in Cantonese, two independent studies, a family-based association study and a case–control study, were conducted using the haplotype-tagging single-nucleotide polymorphism approach. A total of 2499 individuals from 546 nuclear families were initially genotyped for the family-based association study. Single-nucleotide polymorphisms (SNPs) rs9418990, rs915908, rs8192780, rs1536826, rs3827688 and one haplotype h2 (CGTGTTAA) were revealed to be significantly associated with the NPC phenotype (P = 0.045–0.003 and P = 0.003, respectively). To follow up the initial study, a case–control study including 755 cases and 755 controls was conducted. Similar results were observed in the case–control study in individuals <46 years of age and had a history of cigarette smoking, with odds ratios (ORs) of specific genotypes ranging from 1.88 to 2.99 corresponding to SNP rs9418990, rs3813865, rs915906, rs2249695, rs8192780, rs1536826, rs3827688 and of haplotypes h2 with OR = 1.65 (P = 0.026), h5 (CCCGTTAA) with OR = 2.58 (P = 0.007). The values of false-positive report probability were <0.015 for six SNPs, suggesting that the reported associations are less probably to be false. This study provides robust evidence for associations between genetic variants of CYP2E1 and NPC risk. PMID:19805575

  17. Correction of population stratification in large multi-ethnic association studies.

    Directory of Open Access Journals (Sweden)

    David Serre

    2008-01-01

    Full Text Available The vast majority of genetic risk factors for complex diseases have, taken individually, a small effect on the end phenotype. Population-based association studies therefore need very large sample sizes to detect significant differences between affected and non-affected individuals. Including thousands of affected individuals in a study requires recruitment in numerous centers, possibly from different geographic regions. Unfortunately such a recruitment strategy is likely to complicate the study design and to generate concerns regarding population stratification.We analyzed 9,751 individuals representing three main ethnic groups - Europeans, Arabs and South Asians - that had been enrolled from 154 centers involving 52 countries for a global case/control study of acute myocardial infarction. All individuals were genotyped at 103 candidate genes using 1,536 SNPs selected with a tagging strategy that captures most of the genetic diversity in different populations. We show that relying solely on self-reported ethnicity is not sufficient to exclude population stratification and we present additional methods to identify and correct for stratification.Our results highlight the importance of carefully addressing population stratification and of carefully "cleaning" the sample prior to analyses to obtain stronger signals of association and to avoid spurious results.

  18. Oral contraceptive use is associated with prostate cancer: an ecological study.

    Science.gov (United States)

    Margel, David; Fleshner, Neil E

    2011-01-01

    Background Several recent studies have suggested that oestrogen exposure may increase the risk of prostate cancer (PCa). Objectives To examine associations between PCa incidence and mortality and population-based use of oral contraceptives (OCs). It was hypothesised that OC by-products may cause environmental contamination, leading to an increased low level oestrogen exposure and therefore higher PCa incidence and mortality. Methods The hypothesis was tested in an ecological study. Data from the International Agency for Research on Cancer were used to retrieve age-standardised rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report were used to retrieve data on contraceptive use. A Pearson correlation and multivariable linear regression were used to associate the percentage of women using OCs, intrauterine devices, condoms or vaginal barriers to the age standardised prostate cancer incidence and mortality. These analyses were performed by individual nations and by continents worldwide. Results OC use was significantly associated with prostate cancer incidence and mortality in the individual nations worldwide (r=0.61 and r=0.53, respectively; pnation's wealth. Conclusion A significant association between OCs and PCa has been shown. It is hypothesised that the OC effect may be mediated through environmental oestrogen levels; this novel concept is worth further investigation.

  19. Musculoskeletal Problems Associated with University Students Computer Users: A Cross-Sectional Study

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    Rakhadani PB

    2017-07-01

    Full Text Available While several studies have examined the prevalence and correlates of musculoskeletal problems among university students, scanty information exists in South African context. The objective of this study was to determine the prevalence, causes and consequences of musculoskeletal problems among University of Venda students’ computer users. This cross-sectional study involved 694 university students at the University of Venda. A self-designed questionnaire was used to collect information on the sociodemographic characteristics, problems associated with computer users, and causes of musculoskeletal problems associated with computer users. The majority (84.6% of the participants use computer for internet, wording processing (20.3%, and games (18.7%. The students reported neck pain when using computer (52.3%; shoulder (47.0%, finger (45.0%, lower back (43.1%, general body pain (42.9%, elbow (36.2%, wrist (33.7%, hip and foot (29.1% and knee (26.2%. Reported causes of musculoskeletal pains associated with computer usage were: sitting position, low chair, a lot of time spent on computer, uncomfortable laboratory chairs, and stressfulness. Eye problems (51.9%, muscle cramp (344.0%, headache (45.3%, blurred vision (38.0%, feeling of illness (39.9% and missed lectures (29.1% were consequences of musculoskeletal problems linked to computer use. The majority of students reported having mild pain (43.7%, moderate (24.2%, and severe (8.4% pains. Years of computer use were significantly associated with neck, shoulder and wrist pain. Using computer for internet was significantly associated with neck pain (OR=0.60; 95% CI 0.40-0.93; games: neck (OR=0.60; 95% CI 0.40-0.85 and hip/foot (OR=0.60; CI 95% 0.40-0.92, programming for elbow (OR= 1.78; CI 95% 1.10-2.94 and wrist (OR=2.25; CI 95% 1.36-3.73, while word processing was significantly associated with lower back (OR=1.45; CI 95% 1.03-2.04. Undergraduate study had a significant association with elbow pain (OR=2

  20. A genome-wide association study of serum uric acid in African Americans

    Directory of Open Access Journals (Sweden)

    Gerry Norman P

    2011-02-01

    Full Text Available Abstract Background Uric acid is the primary byproduct of purine metabolism. Hyperuricemia is associated with body mass index (BMI, sex, and multiple complex diseases including gout, hypertension (HTN, renal disease, and type 2 diabetes (T2D. Multiple genome-wide association studies (GWAS in individuals of European ancestry (EA have reported associations between serum uric acid levels (SUAL and specific genomic loci. The purposes of this study were: 1 to replicate major signals reported in EA populations; and 2 to use the weak LD pattern in African ancestry population to better localize (fine-map reported loci and 3 to explore the identification of novel findings cognizant of the moderate sample size. Methods African American (AA participants (n = 1,017 from the Howard University Family Study were included in this study. Genotyping was performed using the Affymetrix® Genome-wide Human SNP Array 6.0. Imputation was performed using MACH and the HapMap reference panels for CEU and YRI. A total of 2,400,542 single nucleotide polymorphisms (SNPs were assessed for association with serum uric acid under the additive genetic model with adjustment for age, sex, BMI, glomerular filtration rate, HTN, T2D, and the top two principal components identified in the assessment of admixture and population stratification. Results Four variants in the gene SLC2A9 achieved genome-wide significance for association with SUAL (p-values ranging from 8.88 × 10-9 to 1.38 × 10-9. Fine-mapping of the SLC2A9 signals identified a 263 kb interval of linkage disequilibrium in the HapMap CEU sample. This interval was reduced to 37 kb in our AA and the HapMap YRI samples. Conclusions The most strongly associated locus for SUAL in EA populations was also the most strongly associated locus in this AA sample. This finding provides evidence for the role of SLC2A9 in uric acid metabolism across human populations. Additionally, our findings demonstrate the utility of following-up EA

  1. 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...

  2. A genome-wide association study of social genetic effects in Landrace pigs.

    Science.gov (United States)

    Hong, Joon Ki; Jeong, Yong Dae; Cho, Eun Seok; Choi, Tae Jeong; Kim, Yong Min; Cho, Kyu Ho; Lee, Jae Bong; Lim, Hyun Tae; Lee, Deuk Hwan

    2018-06-01

    The genetic effects of an individual on the phenotypes of its social partners, such as its pen mates, are known as social genetic effects. This study aims to identify the candidate genes for social (pen-mates') average daily gain (ADG) in pigs by using the genome-wide association approach. Social ADG (sADG) was the average ADG of unrelated pen-mates (strangers). We used the phenotype data (16,802 records) after correcting for batch (week), sex, pen, number of strangers (1 to 7 pigs) in the pen, full-sib rate (0% to 80%) within pen, and age at the end of the test. A total of 1,041 pigs from Landrace breeds were genotyped using the Illumina PorcineSNP60 v2 BeadChip panel, which comprised 61,565 single nucleotide polymorphism (SNP) markers. After quality control, 909 individuals and 39,837 markers remained for sADG in genome-wide association study. We detected five new SNPs, all on chromosome 6, which have not been associated with social ADG or other growth traits to date. One SNP was inside the prostaglandin F2α receptor ( PTGFR ) gene, another SNP was located 22 kb upstream of gene interferon-induced protein 44 ( IFI44 ), and the last three SNPs were between 161 kb and 191 kb upstream of the EGF latrophilin and seven transmembrane domain-containing protein 1 ( ELTD1 ) gene. PTGFR, IFI44, and ELTD1 were never associated with social interaction and social genetic effects in any of the previous studies. The identification of several genomic regions, and candidate genes associated with social genetic effects reported here, could contribute to a better understanding of the genetic basis of interaction traits for ADG. In conclusion, we suggest that the PTGFR, IFI44, and ELTD1 may be used as a molecular marker for sADG, although their functional effect was not defined yet. Thus, it will be of interest to execute association studies in those genes.

  3. Evidence for association between Disrupted-in-schizophrenia 1 (DISC1 gene polymorphisms and autism in Chinese Han population: a family-based association study

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    Ruan Yan

    2011-05-01

    Full Text Available Abstract Background Disrupted-in-Schizophrenia 1 (DISC1 gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism. Methods We genotyped seven tag single nucleotide polymorphisms (SNPs in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT and Haploview software. Results We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02. After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values. Conclusions Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.

  4. Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes

    Science.gov (United States)

    Sharma, Swarkar; Gao, Xiaochong; Londono, Douglas; Devroy, Shonn E.; Mauldin, Kristen N.; Frankel, Jessica T.; Brandon, January M.; Zhang, Dongping; Li, Quan-Zhen; Dobbs, Matthew B.; Gurnett, Christina A.; Grant, Struan F.A.; Hakonarson, Hakon; Dormans, John P.; Herring, John A.; Gordon, Derek; Wise, Carol A.

    2011-01-01

    Adolescent idiopathic scoliosis (AIS) is an unexplained and common spinal deformity seen in otherwise healthy children. Its pathophysiology is poorly understood despite intensive investigation. Although genetic underpinnings are clear, replicated susceptibility loci that could provide insight into etiology have not been forthcoming. To address these issues, we performed genome-wide association studies (GWAS) of ∼327 000 single nucleotide polymorphisms (SNPs) in 419 AIS families. We found strongest evidence of association with chromosome 3p26.3 SNPs in the proximity of the CHL1 gene (P protein related to Robo3. Mutations in the Robo3 protein cause horizontal gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Other top associations in our GWAS were with SNPs in the DSCAM gene encoding an axon guidance protein in the same structural class with Chl1 and Robo3. We additionally found AIS associations with loci in CNTNAP2, supporting a previous study linking this gene with AIS. Cntnap2 is also of functional interest, as it interacts directly with L1 and Robo class proteins and participates in axon pathfinding. Our results suggest the relevance of axon guidance pathways in AIS susceptibility, although these findings require further study, particularly given the apparent genetic heterogeneity in this disease. PMID:21216876

  5. Identification of Promising Mutants Associated with Egg Production Traits Revealed by Genome-Wide Association Study.

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    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.

  6. Genome-wide Association Study for Ovarian Cancer Susceptibility using Pooled DNA

    Science.gov (United States)

    Lu, Yi; Chen, Xiaoqing; Beesley, Jonathan; Johnatty, Sharon E.; deFazio, Anna; Lambrechts, Sandrina; Lambrechts, Diether; Despierre, Evelyn; Vergotes, Ignace; Chang-Claude, Jenny; Hein, Rebecca; Nickels, Stefan; Wang-Gohrke, Shan; Dörk, Thilo; Dürst, Matthias; Antonenkova, Natalia; Bogdanova, Natalia; Goodman, Marc T.; Lurie, Galina; Wilkens, Lynne R.; Carney, Michael E.; Butzow, Ralf; Nevanlinna, Heli; Heikkinen, Tuomas; Leminen, Arto; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; van Altena, Anne M.; Aben, Katja K.; Kjaer, Susanne Krüger; Høgdall, Estrid; Jensen, Allan; Brooks-Wilson, Angela; Le, Nhu; Cook, Linda; Earp, Madalene; Kelemen, Linda; Easton, Douglas; Pharoah, Paul; Song, Honglin; Tyrer, Jonathan; Ramus, Susan; Menon, Usha; Gentry-Maharaj, Alexandra; Gayther, Simon A.; Bandera, Elisa V.; Olson, Sara H.; Orlow, Irene; Rodriguez-Rodriguez, Lorna

    2013-01-01

    Recent genome-wide association studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate or low penetrance variants exist among the subset of SNPs not well tagged by the genotyping arrays used in the previous studies which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high density Illumina 1M-Duo array. We followed up 20 of the most significantly associated SNPs, which are not well tagged by the lower density arrays used by the published GWAS, and genotyping them on individual DNA. Most of the top 20 SNPs were clearly validated by individually genotyping the samples used in the pools. However, none of the 20 SNPs replicated when tested for association in a much larger stage 2 set of 4,651 cases and 6,966 controls from the Ovarian Cancer Association Consortium. Given that most of the top 20 SNPs from pooling were validated in the same samples by individual genotyping, the lack of replication is likely to be due to the relatively small sample size in our stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by the less dense arrays. However our study lacked power to make clear statements on the existence of hitherto untagged small effect variants. PMID:22794196

  7. Associations of low grade inflammation and endothelial dysfunction with depression - The Maastricht Study

    DEFF Research Database (Denmark)

    van Dooren, Fleur E P; Schram, Miranda T; Schalkwijk, Casper G

    2016-01-01

    E-Selectin) were univariately associated with depressive symptoms and depressive disorder. The sum scores of inflammation and endothelial dysfunction were associated with depressive disorder after adjustment for age, sex, type 2 diabetes, kidney function and prior cardiovascular disease (OR 1.54, p=0.001 and 1......BACKGROUND: The pathogenesis of depression may involve low-grade inflammation and endothelial dysfunction. We aimed to evaluate the independent associations of inflammation and endothelial dysfunction with depressive symptoms and depressive disorder, and the role of lifestyle factors...... in this association. METHODS: In The Maastricht Study, a population-based cohort study (n=852, 55% men, m=59.8±8.5years), depressive symptoms were assessed with the Patient Health Questionnaire-9 and (major and minor) depressive disorder with the Mini-International Neuropsychiatric Interview. Plasma biomarkers...

  8. Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

    Science.gov (United States)

    Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán

    2014-01-01

    Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186

  9. 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.

  10. Reporting of Human Genome Epidemiology (HuGE association studies: An empirical assessment

    Directory of Open Access Journals (Sweden)

    Gwinn Marta

    2008-05-01

    Full Text Available Abstract Background Several thousand human genome epidemiology association studies are published every year investigating the relationship between common genetic variants and diverse phenotypes. Transparent reporting of study methods and results allows readers to better assess the validity of study findings. Here, we document reporting practices of human genome epidemiology studies. Methods Articles were randomly selected from a continuously updated database of human genome epidemiology association studies to be representative of genetic epidemiology literature. The main analysis evaluated 315 articles published in 2001–2003. For a comparative update, we evaluated 28 more recent articles published in 2006, focusing on issues that were poorly reported in 2001–2003. Results During both time periods, most studies comprised relatively small study populations and examined one or more genetic variants within a single gene. Articles were inconsistent in reporting the data needed to assess selection bias and the methods used to minimize misclassification (of the genotype, outcome, and environmental exposure or to identify population stratification. Statistical power, the use of unrelated study participants, and the use of replicate samples were reported more often in articles published during 2006 when compared with the earlier sample. Conclusion We conclude that many items needed to assess error and bias in human genome epidemiology association studies are not consistently reported. Although some improvements were seen over time, reporting guidelines and online supplemental material may help enhance the transparency of this literature.

  11. Effectiveness of strategies to increase the validity of findings from association studies: size vs. replication

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    Kallischnigg Gerd

    2010-05-01

    Full Text Available Abstract Background The capacity of multiple comparisons to produce false positive findings in genetic association studies is abundantly clear. To address this issue, the concept of false positive report probability (FPRP measures "the probability of no true association between a genetic variant and disease given a statistically significant finding". This concept involves the notion of prior probability of an association between a genetic variant and a disease, making it difficult to achieve acceptable levels for the FPRP when the prior probability is low. Increasing the sample size is of limited efficiency to improve the situation. Methods To further clarify this problem, the concept of true report probability (TRP is introduced by analogy to the positive predictive value (PPV of diagnostic testing. The approach is extended to consider the effects of replication studies. The formula for the TRP after k replication studies is mathematically derived and shown to be only dependent on prior probability, alpha, power, and number of replication studies. Results Case-control association studies are used to illustrate the TRP concept for replication strategies. Based on power considerations, a relationship is derived between TRP after k replication studies and sample size of each individual study. That relationship enables study designers optimization of study plans. Further, it is demonstrated that replication is efficient in increasing the TRP even in the case of low prior probability of an association and without requiring very large sample sizes for each individual study. Conclusions True report probability is a comprehensive and straightforward concept for assessing the validity of positive statistical testing results in association studies. By its extension to replication strategies it can be demonstrated in a transparent manner that replication is highly effective in distinguishing spurious from true associations. Based on the generalized TRP

  12. Genetic association study of common mitochondrial variants on body fat mass.

    Directory of Open Access Journals (Sweden)

    Tie-Lin Yang

    Full Text Available Mitochondria play a central role in ATP production and energy metabolism. Previous studies suggest that common variants in mtDNA are associated with several common complex diseases, including obesity. To test the hypothesis that common mtDNA variants influence obesity-related phenotypes, including BMI and body fat mass, we genotyped a total of 445 mtSNPs across the whole mitochondrial genome in a large sample of 2,286 unrelated Caucasian subjects. 72 of these 445 mtSNPs passed quality control criteria, and were used for subsequent analyses. We also classified all subjects into nine common European haplogroups. Association analyses were conducted for both BMI and body fat mass with single mtSNPs and mtDNA haplogroups. Two mtSNPs, mt4823 and mt8873 were detected to be significantly associated with body fat mass, with adjusted P values of 4.94 × 10⁻³ and 4.58 × 10⁻², respectively. The minor alleles mt4823 C and mt8873 A were associated with reduced fat mass values and the effect size (β was estimated to be 3.52 and 3.18, respectively. These two mtSNPs also achieved nominally significant levels for association with BMI. For haplogroup analyses, we found that haplogroup X was strongly associated with both BMI (adjusted P = 8.31 × 10⁻³ and body fat mass (adjusted P = 5.67×10⁻⁴ Subjects classified as haplogroup X had lower BMI and fat mass values, with the β estimated to be 2.86 and 6.03, respectively. Our findings suggest that common variants in mitochondria might play a role in variations of body fat mass. Further molecular and functional studies will be needed to clarify the potential mechanism.

  13. 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 ...

  14. A Comprehensive Study of Costs Associated With Recurrent Clostridium difficile Infection.

    Science.gov (United States)

    Rodrigues, Rodrigo; Barber, Grant E; Ananthakrishnan, Ashwin N

    2017-02-01

    BACKGROUND Clostridium difficile infection (CDI) is the most common healthcare-associated infection and is associated with considerable morbidity. Recurrent CDI is a key contributing factor to this morbidity. Despite an estimated 83,000 recurrences annually in the United States, there are few accurate estimates of costs associated with recurrent CDI. OBJECTIVE We performed this study (1) to identify the health consequences of recurrent CDI including need for repeat hospitalization, intensive care unit (ICU) stay, and surgery; (2) to determine costs associated with recurrent CDI and identify determinants of such costs; and (3) to compare the outcomes and costs of recurrent CDI to those who develop reinfection. METHODS We identified all patients with confirmed recurrent CDI between January to December 2013 at a single referral center. Healthcare burden associated with recurrence including diagnostic testing, pharmacologic treatment, and inpatient and outpatient healthcare visits were identified in the 12 months following the first recurrence. Total healthcare costs were calculated, and the predictors of high healthcare utilization were identified. RESULTS Our study population included 98 patients with recurrent CDI. The median interval between the initial infection and recurrence was 37 days. The mean age of the cohort was 67 years, two-thirds were women (62%), and the mean Charlson index was 8.6. During the year following the first recurrence of CDI, each patient underwent a mean of 4.4 stool C. difficile toxin tests and received a mean of 2.5 prescriptions for oral vancomycin (range, 0-6). Most patients (84%) with recurrence had a CDI-related hospitalization, and 6% underwent colectomy. The mean total CDI-associated cost was $34,104 per patient, with hospitalization costs accounting for 68%, surgery 20%, and drug treatment 8% of this cost, respectively. Extrapolating to the United States overall, we estimate an annual cost of $2.8 billion related to recurrent CDI

  15. Antifungal prophylaxis in chemotherapy-associated neutropenia: a retrospective, observational study

    Directory of Open Access Journals (Sweden)

    Martin Thomas

    2007-07-01

    Full Text Available Abstract Background In August 2002, the antifungal prophylaxis algorithm for neutropenic hematology/oncology (NHO patients at the Medical Center was changed from conventional amphotericin (AMB to an azole (AZ based regimen (fluconazole [FLU] in low-risk and voriconazole [VOR] in high-risk patients. The aim of our study was to compare outcomes associated with the two regimens, including breakthrough fungal infection, adverse drug events, and costs. Methods Adult, non-febrile, NHO patients who received prophylactic AMB from 8/01/01-7/30/02 or AZ from 8/01/02-7/30/03 were retrospectively evaluated. Results A total of 370 patients (AMB: n = 181; AZ: n = 216 associated with 580 hospitalizations (AMB: n = 259; AZ: n = 321 were included. The incidence of probable/definite breakthrough Aspergillus infections was similar among regimens (AMB: 1.9% vs AZ: 0.6%; p=0.19. A greater incidence of mild/moderate (24.7% vs. 5.3%; p $9,000 increase in mean total costs/hospitalization, the mean acquisition cost associated with AZ was only $947/hospitalization more than AMB. Conclusion While an AZ-based regimen is associated with increased cost, the reduced rate of nephrotoxicity and availability of oral dosage forms, suggests that azoles be used preferentially over AMB. However, an increased rate of severe hepatic toxicity may be associated with VOR.

  16. 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.

  17. Exploring association between sleep deprivation and chronic periodontitis: A pilot study

    Directory of Open Access Journals (Sweden)

    Vishakha Grover

    2015-01-01

    Full Text Available Background: Sleep deprivation has become a global phenomenon, and epidemiologic data indicate that short sleep duration adversely impacts human physical health. Underlying mechanisms involve modulation of immune-inflammatory mechanisms. These changes might contribute to potentiation of destructive periodontal disease. Therefore, the present study aimed to assess if there is an association of sleep deprivation with chronic periodontal diseases. Materials and Methods: Sixty subjects were categorized into 3 groups (n = 20 each viz. clinically healthy, gingivitis and periodontitis. Periodontal status of subjects was assessed by gingival index and pocket probing depth. All the study subjects were administered Pittsburgh Sleep Quality Index (PSQI questionnaire for the assessment of sleep deprivation. Results: Present investigation revealed that mean PSQI was highest in the periodontitis group as compared to other two groups and the difference among three groups was statistically significant. Conclusion: The present study with preliminary results suggestive of the association of sleep deprivation with severity of periodontal disease, definitely calls on for future studies with larger samples.

  18. Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study.

    Science.gov (United States)

    Kasperaviciūte, Dalia; Catarino, Claudia B; Heinzen, Erin L; Depondt, Chantal; Cavalleri, Gianpiero L; Caboclo, Luis O; Tate, Sarah K; Jamnadas-Khoda, Jenny; Chinthapalli, Krishna; Clayton, Lisa M S; Shianna, Kevin V; Radtke, Rodney A; Mikati, Mohamad A; Gallentine, William B; Husain, Aatif M; Alhusaini, Saud; Leppert, David; Middleton, Lefkos T; Gibson, Rachel A; Johnson, Michael R; Matthews, Paul M; Hosford, David; Heuser, Kjell; Amos, Leslie; Ortega, Marcos; Zumsteg, Dominik; Wieser, Heinz-Gregor; Steinhoff, Bernhard J; Krämer, Günter; Hansen, Jörg; Dorn, Thomas; Kantanen, Anne-Mari; Gjerstad, Leif; Peuralinna, Terhi; Hernandez, Dena G; Eriksson, Kai J; Kälviäinen, Reetta K; Doherty, Colin P; Wood, Nicholas W; Pandolfo, Massimo; Duncan, John S; Sander, Josemir W; Delanty, Norman; Goldstein, David B; Sisodiya, Sanjay M

    2010-07-01

    Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio<1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies.

  19. 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...

  20. 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

  1. Heritability studies of yield and yield associated traits in bread wheat

    International Nuclear Information System (INIS)

    Laghari, K.A.; Sial, M.A.; Arain, M.A.; Mirbahar, A.A.; Pirzada, A.; Mancrio, S.M.; Dahot, M.U.

    2010-01-01

    Heritability studies provide valid information about the traits that are transmitted from parents to offspring and also to the successive generations. Such studies help plant breeders to predict a successful cross with high heritability transmission to the progeny and thus are useful in the incorporation of characters into the offspring. Heritability study was conducted in F5 segregating generation of a cross between HT5 (female) and HT 37 (male) of bread wheat. The genetic parameters calculated were genetic variance (Vg,), environmental variance (Ve) and heritability percentage in broad sense (h2%), genetic advance (GA) and heritability coefficient (H). The highest heritability was observed for spike length (79.3%), number of grains per spike (54.5%) and main spike yield (69.5%) associated with high genetic advance (2.8, 22.8 and 1.5 respectively). Moderate to high heritability were recorded for peduncle length (48.75%) and number of grains per spikelet (47.2%) which associated with high genetic advance (2.3 and 0.68 respectively). However awn length and plant height had shown acceptable heritability values. The present finding suggests that most of the yield associated traits have been successfully transmitted. The information generated will be helpful for better understanding and selection of suitable, desirable material especially in advance generations. (author)

  2. Associated Variables of Myositis in Systemic Lupus Erythematosus: A Cross-Sectional Study.

    Science.gov (United States)

    Liang, Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

    2017-05-26

    BACKGROUND This study aimed to estimate the point prevalence of myositis and identify associated variables of myositis in systemic lupus erythematosus (SLE). MATERIAL AND METHODS Clinical date of patients hospitalized with lupus at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital were collected. Patients were defined as having myositis if they reported the presence of persistent invalidating muscular weakness combined with increased levels of creatine phosphokinase (CPK) and abnormal electromyography (EMG). RESULTS The study sample comprised 1701 lupus patients, of which 44 had myositis. Patients with SLE-associated myositis are more likely to have skin rash, alopecia, pericarditis, vasculitis, anti-Sm, anti-RNP, anti-dsDNA, thrombocytopenia, leukopenia, low C3, low C4, high erythrocyte sedimentation rate (ESR), high D-dimer, and active disease. Multivariate logistic regression found positive associations between leukopenia, alopecia, and active disease with myositis. Negative associations between myositis with the use of corticosteroids or immunosuppressive drugs were revealed in univariate and multivariate analysis. CONCLUSIONS The point prevalence of myositis was 2.6% in SLE patients. The significant association of alopecia, leukopenia, and active disease with myositis suggests that organ damage, hematological abnormality, and high disease activity promote the progression of myositis in lupus patients.

  3. Incident Trichomonas vaginalis Is Associated With Partnership Concurrency: A Longitudinal Cohort Study.

    Science.gov (United States)

    Kenyon, Chris R; Buyze, Jozefien; Klebanoff, Mark; Brotman, Rebecca M

    2017-11-01

    Sexual partner concurrency (PC) has been shown to be a risk factor for a number of sexually transmitted infections but it is unknown if it is a risk factor for Trichomonas vaginalis (TV). We assess if there is an association between PC and incident TV infection. We used mixed effects logistic regression to assess the association between PC and incident TV in the Longitudinal Study of Vaginal Flora, a cohort study of 3620 women followed quarterly for 5 visits. Trichomonas vaginalis was more common in those reporting definite/possible/unknown PC (15.6%/15.0%/18.3%) than those reporting no PC (5.2%; P < 0.001 for all 3 comparisons). After controlling for a range of confounders, incident TV remained associated with reporting that one's partner definitely (adjusted odds ratio, 5.4; 95% confidence interval, 3.7-8.0) and possibly (adjusted odds ratio, 3.4; 95% confidence interval, 2.2-5.1) engaged in PC in the preceding period. Partner concurrency was associated with incident TV infection.

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  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 cohort...

  9. 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...

  10. An evolutionary framework for association testing in resequencing studies.

    Directory of Open Access Journals (Sweden)

    C Ryan King

    2010-11-01

    Full Text Available Sequencing technologies are becoming cheap enough to apply to large numbers of study participants and promise to provide new insights into human phenotypes by bringing to light rare and previously unknown genetic variants. We develop a new framework for the analysis of sequence data that incorporates all of the major features of previously proposed approaches, including those focused on allele counts and allele burden, but is both more general and more powerful. We harness population genetic theory to provide prior information on effect sizes and to create a pooling strategy for information from rare variants. Our method, EMMPAT (Evolutionary Mixed Model for Pooled Association Testing, generates a single test per gene (substantially reducing multiple testing concerns, facilitates graphical summaries, and improves the interpretation of results by allowing calculation of attributable variance. Simulations show that, relative to previously used approaches, our method increases the power to detect genes that affect phenotype when natural selection has kept alleles with large effect sizes rare. We demonstrate our approach on a population-based re-sequencing study of association between serum triglycerides and variation in ANGPTL4.

  11. Associations Between Adiposity and Metabolic Syndrome Over Time: The Healthy Twin Study.

    Science.gov (United States)

    Song, Yun-Mi; Sung, Joohon; Lee, Kayoung

    2017-04-01

    We evaluated the association between changes in adiposity traits including anthropometric and fat mass indicators and changes in metabolic syndrome traits including metabolic syndrome clustering and individual components over time. We also assessed the shared genetic and environmental correlations between the two traits. Participants were 284 South Korean twin individuals and 279 nontwin family members had complete data for changes in adiposity traits and metabolic syndrome traits of the Healthy Twin study. Mixed linear model and bivariate variance-component analysis were applied. Over a period of 3.1 ± 0.6 years of study, changes in adiposity traits [body mass index (BMI), waist circumference, total fat mass, and fat mass to lean mass ratio] had significant associations with changes in metabolic syndrome clustering [high blood pressure, high serum glucose, high triglycerides (TG), and low high-density lipoprotein cholesterol] after adjusting for intra-familial and sibling correlations, age, sex, baseline metabolic syndrome clustering, and socioeconomic factors and health behaviors at follow-up. Change in BMI associated significantly with changes in individual metabolic syndrome components compared to other adiposity traits. Change in metabolic syndrome component TG was a better predictor of changes in adiposity traits compared to changes in other metabolic components. These associations were explained by significant environmental correlations but not by genetic correlations. Changes in anthropometric and fat mass indicators were positively associated with changes in metabolic syndrome clustering and those associations appeared to be regulated by environmental influences.

  12. Inverse association between atopy and melanoma: A case-control study

    NARCIS (Netherlands)

    Marasigan, V. (Vivien); M.-A. Morren (Marie-Anne); J. Lambert; Medaer, K. (Karen); Fieuws, S. (Steffen); T.E.C. Nijsten (Tamar); Garmyn, M. (Marjan)

    2017-01-01

    textabstractHeightened cutaneous immune surveillance in atopic patients may inhibit development of melanoma. The aim of this study was to analyse the association between atopy and melanoma (development and outcome). A total of 188 cases of melanoma and 596 healthy controls were interviewed by

  13. Genomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders

    NARCIS (Netherlands)

    Cichon, S.; Craddock, N.; Daly, M.J.; Faraone, S.V.; Gejman, P.V.; Kelsoe, J.; Lehner, T.; Levinson, D.F.; Moran, A.P.; Sklar, P.; Sullivan, P.F.; Boomsma, D.I.; de Geus, E.J.C.; Posthuma, D.; Willemsen, G.

    2009-01-01

    Objective: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. Method: A literature review was carried out, power and other issues

  14. Genomewide association studies: history, rationale, and prospects for psychiatric disorders.

    NARCIS (Netherlands)

    Franke, B.; Buitelaar, J.K.; Cichon, S.; Craddock, N.; Daly, M.; Faraone, S.V.; Gejman, P.V.; Kelsoe, J.; Lehner, T.; Levinson, D.F.; Moran, A.; Sklar, P.; Sullivan, P.F.

    2009-01-01

    OBJECTIVE: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. METHOD: A literature review was carried out, power and other issues

  15. 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...

  16. Association between periodontal disease and gestational diabetes mellitus (GDM) - a prospective cohort study.

    Science.gov (United States)

    Kumar, Ashok; Sharma, Deepika S; Verma, Mahesh; Lamba, Arundeep Kaur; Gupta, Madhavi M; Sharma, Shashi; Perumal, Vanamail

    2018-04-03

    The present study aims to determine the association between periodontal disease and gestational diabetes mellitus (GDM) and the effect of this association on pregnancy outcome in North Indian population. A total of 584 primigravidae were recruited at 12-14 weeks of gestation. Their periodontal examination was done along with 75g oral glucose load test at the time of recruitment. GDM was diagnosed as per the DIPSI (The Diabetes in Pregnancy Study group India) guidelines (≥140mg/dL). Women with normal plasma glucose values underwent a repeat 75g oral glucose load test at 24-28 weeks of gestation. All patients were followed up for pregnancy outcomes. Out of 584 primigravida, 184 (31.5%) had gingivitis and 148 (25.3%) had periodontitis. Overall, 332 (56.8%) pregnant women had periodontal disease. It was associated with GDM with adjusted hazard ratio (aHR) of 2.85 (95%CI=1.47-5.53). The occurrence of preeclampsia was associated with periodontal disease with aHR of 2.20 (95%CI=0.86-5.60). If primigravidae had periodontal disease along with GDM, the risk of preeclampsia had shown increased aHR of 18.79 (95% CI= 7.45 - 47.40). The study shows a significant association of periodontal disease with GDM and an increased risk of developing preeclampsia due to this association. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Born to Lead? A Twin Design and Genetic Association Study of Leadership Role Occupancy*

    Science.gov (United States)

    De Neve, Jan-Emmanuel; Mikhaylov, Slava; Dawes, Christopher T.; Christakis, Nicholas A.; Fowler, James H.

    2013-01-01

    We address leadership emergence and the possibility that there is a partially innate predisposition to occupy a leadership role. Employing twin design methods on data from the National Longitudinal Study of Adolescent Health, we estimate the heritability of leadership role occupancy at 24%. Twin studies do not point to specific genes or neurological processes that might be involved. We therefore also conduct association analysis on the available genetic markers. The results show that leadership role occupancy is associated with rs4950, a single nucleotide polymorphism (SNP) residing on a neuronal acetylcholine receptor gene (CHRNB3). We replicate this family-based genetic association result on an independent sample in the Framingham Heart Study. This is the first study to identify a specific genotype associated with the tendency to occupy a leadership position. The results suggest that what determines whether an individual occupies a leadership position is the complex product of genetic and environmental influences; with a particular role for rs4950. PMID:23459689

  18. Quantifying the underestimation of relative risks from genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Chris Spencer

    2011-03-01

    Full Text Available Genome-wide association studies (GWAS have identified hundreds of associated loci across many common diseases. Most risk variants identified by GWAS will merely be tags for as-yet-unknown causal variants. It is therefore possible that identification of the causal variant, by fine mapping, will identify alleles with larger effects on genetic risk than those currently estimated from GWAS replication studies. We show that under plausible assumptions, whilst the majority of the per-allele relative risks (RR estimated from GWAS data will be close to the true risk at the causal variant, some could be considerable underestimates. For example, for an estimated RR in the range 1.2-1.3, there is approximately a 38% chance that it exceeds 1.4 and a 10% chance that it is over 2. We show how these probabilities can vary depending on the true effects associated with low-frequency variants and on the minor allele frequency (MAF of the most associated SNP. We investigate the consequences of the underestimation of effect sizes for predictions of an individual's disease risk and interpret our results for the design of fine mapping experiments. Although these effects mean that the amount of heritability explained by known GWAS loci is expected to be larger than current projections, this increase is likely to explain a relatively small amount of the so-called "missing" heritability.

  19. Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC.

    Directory of Open Access Journals (Sweden)

    Rebecca Hein

    Full Text Available The 6q25.1 locus was first identified via a genome-wide association study (GWAS in Chinese women and marked by single nucleotide polymorphism (SNP rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR and 95% confidence intervals (CI. Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+ versus negative (ER- tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G = 1.36 (95% CI 1.26-1.48, p = 7.6 × 10(-14 in Asians and 1.09 (95% CI 1.07-1.11, p = 6.8 × 10(-18 in Europeans. rs12662670: OR (G/T = 1.29 (95% CI 1.19-1.41, p = 1.2 × 10(-9 in Asians and 1.12 (95% CI 1.08-1.17, p = 3.8 × 10(-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER- = 1.20 (95% CI 1.15-1.25, p = 1.8 × 10(-17 versus OR (ER+ = 1.07 (95% CI 1.04-1.1, p = 1.3 × 10(-7, p(heterogeneity = 5.1 × 10(-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater

  20. Actigraphic sleep fragmentation, efficiency and duration associate with dietary intake in the Rotterdam study

    Science.gov (United States)

    Short self-reported sleep duration is associated with dietary intake and this association may partly mediate the link between short sleep and metabolic abnormalities. Subjective sleep measures, however, may be inaccurate and biased. The objective of this study was to evaluate the associations betwee...

  1. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    NARCIS (Netherlands)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.; Acha, Moshe Ray; Newton-Cheh, Christopher; Pfeufer, Arne; Lyneh, Stacey N.; Olesen, Soren-Peter; Brunak, Soren; Ellinor, Patrick T.; Jukema, J. Wouter; Trompet, Stella; Ford, Ian; Macfarlane, Peter W.; Krijthe, Bouwe P.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.; Nathoe, Hendrik M.; Spiering, Wilko; Daly, Mark J.; Asselbergs, Ikea W.; van der Harst, Pim; Milan, David J.; de Bakker, Paul I. W.; Lage, Kasper; Olsen, Jesper V.

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes

  2. Fasting proinsulin levels are significantly associated with 20 year cancer mortality rates. The Hoorn Study

    NARCIS (Netherlands)

    Walraven, I.; van 't Riet, E.; Stehouwer, C.D.A.; Polak, B.C.P.; Moll, A.C.; Dekker, J.M.; Nijpels, G.

    2013-01-01

    Aims/hypothesis: Proinsulin is possibly associated with cancer through activation of insulin receptor isoform A. We sought to investigate the associations between proinsulin and 20 year cancer mortality rates. Methods: The study was performed within the Hoorn Study, a population-based study of

  3. Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study

    OpenAIRE

    Perera, Minoli A; Cavallari, Larisa H; Limdi, Nita A; Gamazon, Eric R; Konkashbaev, Anuar; Daneshjou, Roxana; Pluzhnikov, Anna; Crawford, Dana C; Wang, Jelai; Liu, Nianjun; Tatonetti, Nicholas; Bourgeois, Stephane; Takahashi, Harumi; Bradford, Yukiko; Burkley, Benjamin M

    2013-01-01

    Summary BackgroundVKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. MethodsWe did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged ≥18 years) who were taking a stable maintenance dose of warfar...

  4. 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...

  5. Association between obesity and selected morbidities: a study of BRICS countries.

    Directory of Open Access Journals (Sweden)

    Ankita Shukla

    Full Text Available OBJECTIVE: Over the past few decades, obesity has reached epidemic proportions, and is a major contributor to the global burden of chronic diseases and disability. There is little evidence on obesity related co-morbidities in BRICS countries. The first objective is to examine the factors associated with overweight and obesity in four of the five BRICS countries (China, India, Russia and South Africa. The second is to examine the linkage of obesity with selected morbidities. METHODS: We used data from the Study on Global Ageing and Adult Health (SAGE survey conducted by the World Health Organization (WHO in China, India, Russia and South Africa during 2007-10. The morbidities included in the analysis are Hypertension, Diabetes, Angina, Stroke, Arthritis and Depression. FINDINGS: The prevalence of obesity was highest in South Africa (35% followed by Russia (22%, China (5% and India (3%. The prevalence of obesity was significantly higher in females as compared to males in all the countries. While the wealth quintile was associated with overweight in India and China, engaging in work requiring physical activity was associated with obesity in China and South Africa. Overweight/obesity was positively associated with Hypertension and Diabetes in all the four countries. Obesity was also positively associated with Arthritis and Angina in China, Russia and South Africa. In comparison, overweight/obesity was not associated with Stroke and Depression in any of the four countries. CONCLUSION: Obesity was statistically associated with Hypertension, Angina, Diabetes and Arthritis in China, Russia and South Africa. In India, obesity was associated only with Hypertension and Diabetes.

  6. Association between obesity and selected morbidities: a study of BRICS countries.

    Science.gov (United States)

    Shukla, Ankita; Kumar, Kaushalendra; Singh, Abhishek

    2014-01-01

    Over the past few decades, obesity has reached epidemic proportions, and is a major contributor to the global burden of chronic diseases and disability. There is little evidence on obesity related co-morbidities in BRICS countries. The first objective is to examine the factors associated with overweight and obesity in four of the five BRICS countries (China, India, Russia and South Africa). The second is to examine the linkage of obesity with selected morbidities. We used data from the Study on Global Ageing and Adult Health (SAGE) survey conducted by the World Health Organization (WHO) in China, India, Russia and South Africa during 2007-10. The morbidities included in the analysis are Hypertension, Diabetes, Angina, Stroke, Arthritis and Depression. The prevalence of obesity was highest in South Africa (35%) followed by Russia (22%), China (5%) and India (3%). The prevalence of obesity was significantly higher in females as compared to males in all the countries. While the wealth quintile was associated with overweight in India and China, engaging in work requiring physical activity was associated with obesity in China and South Africa. Overweight/obesity was positively associated with Hypertension and Diabetes in all the four countries. Obesity was also positively associated with Arthritis and Angina in China, Russia and South Africa. In comparison, overweight/obesity was not associated with Stroke and Depression in any of the four countries. Obesity was statistically associated with Hypertension, Angina, Diabetes and Arthritis in China, Russia and South Africa. In India, obesity was associated only with Hypertension and Diabetes.

  7. Is problem-based learning associated with students’ motivation? A quantitative and qualitative study

    NARCIS (Netherlands)

    M. Wijnen (Marit); S.M.M. Loyens (Sofie); L. Wijnia (Lisette); G. Smeets (Guus); M.J. Kroeze (Maarten); H.T. van der Molen (Henk)

    2017-01-01

    textabstractIn this study, a mixed-method design was employed to investigate the association between a student-centred, problem-based learning (PBL) method and law students’ motivation. Self-determination theory (SDT) states that autonomous motivation, which is associated with higher academic

  8. 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

  9. Associated factors with attention deficit hyperactivity disorder (ADHD): a case-control study.

    Science.gov (United States)

    Malek, Ayyoub; Amiri, Shahrokh; Sadegfard, Majid; Abdi, Salman; Amini, Saeedeh

    2012-09-01

    The current study attempted to investigate factors associated with attention deficit hyperactivity disorder (ADHD) in children without co-morbidities. In this case-control study, 164 ADHD children who attended the Child and Adolescent Psychiatric Clinics of Tabriz University of Medical Sciences, Iran were compared with 166 normal children selected in a random-cluster method from primary and secondary schools. Clinical interviews based on DSM-IV-TR using K-SADS were used to diagnose ADHD cases and to select the control group. Participants were matched for age. We used chi-square and binary logistic regression for data analysis. Among the associated factors with ADHD were gender and maternal employment. Boys (OR 0.54; 95% confidence interval: 0.34 - 0.86) and those children with working mothers (OR 0.16: 95% confidence interval: 0.06 - 0.86) suffered more from ADHD. The birth season, family size, birth order, and parental kinship were not among risk factors for ADHD. The results of the study show that maternal employment and male gender are among the associated risk factors for ADHD.

  10. Use of genome-wide association studies for cancer research and drug repositioning.

    Directory of Open Access Journals (Sweden)

    Jizhun Zhang

    Full Text Available Although genome-wide association studies have identified many risk loci associated with colorectal cancer, the molecular basis of these associations are still unclear. We aimed to infer biological insights and highlight candidate genes of interest within GWAS risk loci. We used an in silico pipeline based on functional annotation, quantitative trait loci mapping of cis-acting gene, PubMed text-mining, protein-protein interaction studies, genetic overlaps with cancer somatic mutations and knockout mouse phenotypes, and functional enrichment analysis to prioritize the candidate genes at the colorectal cancer risk loci. Based on these analyses, we observed that these genes were the targets of approved therapies for colorectal cancer, and suggested that drugs approved for other indications may be repurposed for the treatment of colorectal cancer. This study highlights the use of publicly available data as a cost effective solution to derive biological insights, and provides an empirical evidence that the molecular basis of colorectal cancer can provide important leads for the discovery of new drugs.

  11. Genome-wide association study for ovarian cancer susceptibility using pooled DNA

    DEFF Research Database (Denmark)

    Lu, Yi; Chen, Xiaoqing; Beesley, Jonathan

    2012-01-01

    stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by less dense arrays. However, our study lacked power to make clear statements on the existence of hitherto untagged small......Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used...... in the previous studies, which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high-density Illumina 1M-Duo array. We followed up 20 of the most significantly associated...

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

    Science.gov (United States)

    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. Association between diabetes and causes of dementia: Evidence from a clinicopathological study

    Directory of Open Access Journals (Sweden)

    Maria Niures Pimentel dos Santos Matioli

    Full Text Available ABSTRACT. Background: Diabetes mellitus is a risk factor for dementia, especially for vascular dementia (VaD, but there is no consensus on diabetes as a risk factor for Alzheimer's disease (AD and other causes of dementia. Objective: To explore the association between diabetes and the neuropathological etiology of dementia in a large autopsy study. Methods: Data were collected from the participants of the Brain Bank of the Brazilian Aging Brain Study Group between 2004 and 2015. Diagnosis of diabetes was reported by the deceased's next-of-kin. Clinical dementia was established when CDR ≥ 1 and IQCODE > 3.41. Dementia etiology was determined by neuropathological examination using immunohistochemistry. The association of diabetes with odds of dementia was investigated using multivariate logistic regression. Results: We included 1,037 subjects and diabetes was present in 279 participants (27%. The prevalence of dementia diagnosis was similar in diabetics (29% and non-diabetics (27%. We found no association between diabetes and dementia (OR = 1.22; 95%CI = 0.81-1.82; p = 0.34 on the multivariate analysis. AD was the main cause of dementia in both groups, while VaD was the second-most-frequent cause in diabetics. Other mixed dementia was the second-most-common cause of dementia and more frequent among non-diabetics (p = 0.03. Conclusion: Diabetes was not associated with dementia in this large clinicopathological study.

  14. Association of Aging-Related Endophenotypes With Mortality in 2 Cohort Studies

    DEFF Research Database (Denmark)

    Singh, Jatinder; Schupf, Nicole; Boudreau, Robert

    2015-01-01

    with mortality. The most dominant endophenotype primarily reflected the physical activity and pulmonary domains, was heritable, was significantly associated with mortality, and attenuated the association of age with mortality by 24.1%. Using data (1997-1998) on 1,794 Health, Aging and Body Composition Study...... participants from Memphis, Tennessee, and Pittsburgh, Pennsylvania, we obtained strikingly similar endophenotypes and relationships to mortality. We also reproduced the endophenotype constructs, especially the dominant physical activity and pulmonary endophenotype, within demographic subpopulations of these 2...... data (2006-2009) on 28 traits representing 5 domains (cognitive, cardiovascular, metabolic, physical, and pulmonary) from 4,472 US and Danish individuals in 574 pedigrees from the Long Life Family Study (United States and Denmark), we constructed endophenotypes and assessed their relationship...

  15. 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...

  16. Mortality from respiratory diseases associated with opium use: a population-based cohort study.

    Science.gov (United States)

    Rahmati, Atieh; Shakeri, Ramin; Khademi, Hooman; Poutschi, Hossein; Pourshams, Akram; Etemadi, Arash; Khoshnia, Masoud; Sohrabpour, Amir Ali; Aliasgari, Ali; Jafari, Elham; Islami, Farhad; Semnani, Shahryar; Gharravi, Abdolsamad; Abnet, Christian C; Pharoah, Paul D P; Brennan, Paul; Boffetta, Paolo; Dawsey, Sanford M; Malekzadeh, Reza; Kamangar, Farin

    2017-11-01

    Recent studies have suggested that opium use may increase mortality from cancer and cardiovascular diseases. However, no comprehensive study of opium use and mortality from respiratory diseases has been published. We aimed to study the association between opium use and mortality from respiratory disease using prospectively collected data. We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50 045 adults were enrolled from 2004 to 2008, and followed annually until June 2015, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest. During the follow-up period, 331 deaths from respiratory disease were reported (85 due to respiratory malignancies and 246 due to non-malignant aetiologies). Opium use was associated with an increased risk of death from any respiratory disease (adjusted HR 95% CI 3.13 (2.42 to 4.04)). The association was dose-dependent with a HR of 3.84 (2.61 to 5.67) for the highest quintile of cumulative opium use versus never use (P trend respiratory mortality were 1.96 (1.18 to 3.25) and 3.71 (2.76 to 4.96), respectively. Long-term opium use is associated with increased mortality from both malignant and non-malignant respiratory diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. [Enlightenment from genome-wide association study to genetics of psoriasis].

    Science.gov (United States)

    ZHANG, Xue-jun

    2009-07-01

    Psoriasis is a common autoimmune and hyper proliferative skin disease, characterized by thick, silvery scale patches. Numerous family studies have provided compelling evidence of a genetic predisposition to psoriasis, although the inheritance pattern is unclear. However, few of these studies have achieved consistent results, except for the MHC locus, a problem frequently encountered in the investigation of complex disease. Using high-throughput techniques to genotype hundreds of thousands of single nucleotide polymorphisms explore their relationship with phenotypes, genome-wide association studies (GWAS) are now proven to be a powerful approach for screening the susceptibility genes (loci) of complex disease. Recently, three GWAS on psoriasis published in Nature Genetics have provided us with many novel clues concerning disease pathogenesis, in both immune and non-immune pathways. The MHC locus (HLA-Cw6 and other MHC variance), the major locus involved in the immune reactions of human immune disease, has consistently been shown to be associated with psoriasis, both in previous linkage and present GWAS. IL-12B and IL23R, which are the two non-MHC genes with highly associated evidence with psoriasis in multiple studies performed so far and potent cytokines with complex biological activities, should be of great importance in the pathogenesis of psoriasis. Recent clinical trials, in which anti-IL-12p40 antibodies were used for the treatment of psoriasis, have provided further evidence of the role of IL-12/23 in the pathophysiology of psoriasis,and highlighted a new road of treatment for psoriasis. In 2008,we performed the first large GWAS in the Chinese population and identified a novel susceptibility locus within the late cornified envelope (LCE) gene cluster: LCE3A and LCE3D on chromosome 1q21, with conclusive evidence (rs4085613, p(combined)=6.69*10(-30); odds ratio=0.76). Meanwhile, another group also identified a deletion comprising and LCE gene cluster of LCE3B

  18. Association of UV radiation with Parkinson disease incidence: A nationwide French ecologic study

    International Nuclear Information System (INIS)

    Kravietz, Adam; Kab, Sofiane; Wald, Lucien; Dugravot, Aline; Singh-Manoux, Archana; Moisan, Frédéric; Elbaz, Alexis

    2017-01-01

    Background: Vitamin D is thought to contribute to brain health, but it is unclear whether low vitamin D levels are associated with increased incidence of Parkinson's disease (PD). Using ultraviolet B (UV-B) as a surrogate for vitamin D levels, we conducted a nationwide ecologic study in France in order to examine the association of UV-B with PD incidence. Methods: We used French national drug claims databases to identify PD cases using a validated algorithm. UV-B data from the solar radiation database were derived from satellite images. We estimated PD incidence (2010–2012) at the canton level (small administrative French unit) and used multilevel Poisson regression to examine its association with UV-B (2005 annual average), after adjustment for age, sex, deprivation index, density of neurologists, smoking, proportion of agricultural land, and vitamin D supplementation. Results: Analyses are based on 69,010 incident PD patients. The association between UV-B and PD incidence was quadratic (P<0.001) and modified by age (P<0.001). Below 70y, incidence was higher in the bottom quintile (relative risk, RR Q1:45-49y =1.18, 95% CI=1.08–1.29) compared with the middle UV-B quintile, and lower in the top quintile (RR Q5:45-49y =0.85 [0.77–0.94]). An opposite pattern was observed in older subjects (RR Q1:85-89y =0.92 [0.89–0.96]; RR Q5:85-89y =1.06 [1.02–1.11]). Analysis based on continuous UV-B yielded similar conclusions. Conclusions: In this nationwide study, there was an age-dependent quadratic association between UV-B and PD incidence. This study suggests that reasonable UV-B exposure is associated with lower PD risk in younger persons and that future studies should examine dose-response relations and take age into account. - Highlights: • There is an age-dependent quadratic association between UV-B and PD incidence. • Reasonable UV-B exposure is beneficial in younger persons for the risk of PD. • Our findings are consistent with a role of vitamin D

  19. Study Finds Association between Biological Marker and Susceptibility to the Common Cold

    Science.gov (United States)

    ... W X Y Z Study Finds Association Between Biological Marker and Susceptibility to the Common Cold Share: © ... a cold caused by a particular rhinovirus. The biological marker identified in the study was the length ...

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

    Directory of Open Access Journals (Sweden)

    Ayşe Demirkan

    Full Text Available Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, 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 phosphatidylcholines (PC, 20 lysophosphatidylcholines (LPC, 27 phosphatidylethanolamines (PE, and 16 PE-based plasmalogens (PLPE, as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204 and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57. After a correction for multiple comparisons (P-value<2.2×10(-9, we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1 and two with sphingolipids (PLD2 and APOE explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3 suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2 to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our

  1. Study of the factors associated with substance use in adolescence using Association Rules.

    Science.gov (United States)

    García, Elena Gervilla; Blasco, Berta Cajal; López, Rafael Jiménez; Pol, Alfonso Palmer

    2010-01-01

    The aim of this study is to analyse the factors related to the use of addictive substances in adolescence using association rules, descriptive tools included in Data Mining. Thus, we have a database referring to the consumption of addictive substances in adolescence, and use the free distribution program in the R arules package (version 2.10.0). The sample was made up of 9,300 students between the ages of 14 and 18 (47.1% boys and 52.9% girls) with an average age of 15.6 (SE=1.2). The adolescents answered an anonymous questionnaire on personal, family and environmental risk factors related to substance use. The best rules obtained with regard to substance use relate the consumption of alcohol to perceived parenting style and peer consumption (confidence = 0.8528), the use of tobacco (smoking), cannabis and cocaine to perceived parental action and illegal behaviour (confidence = 0.8032, 0.8718 and 1.0000, respectively), and the use of ecstasy to peer consumption (confidence = 1.0000). In general, the association rules show in a simple manner the relationship between certain patterns of perceived parental action, behaviours that deviate from social behavioural norms, peer consumption and the use of different legal and illegal drugs of abuse in adolescence. The implications of the results obtained are described, together with the usefulness of this new methodology of analysis.

  2. Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women.

    Directory of Open Access Journals (Sweden)

    Guillaume Paré

    2008-07-01

    Full Text Available While circulating levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1 have been associated with diverse conditions including myocardial infarction, stroke, malaria, and diabetes, comprehensive analysis of the common genetic determinants of sICAM-1 is not available. In a genome-wide association study conducted among 6,578 participants in the Women's Genome Health Study, we find that three SNPs at the ICAM1 (19p13.2 locus (rs1799969, rs5498 and rs281437 are non-redundantly associated with plasma sICAM-1 concentrations at a genome-wide significance level (P<5x10(-8, thus extending prior results from linkage and candidate gene studies. We also find that a single SNP (rs507666, P = 5.1x10(-29 at the ABO (9q34.2 locus is highly correlated with sICAM-1 concentrations. The novel association at the ABO locus provides evidence for a previously unknown regulatory role of histo-blood group antigens in inflammatory adhesion processes.

  3. Porcine NAMPT gene: search for polymorphism, mapping and association studies

    Czech Academy of Sciences Publication Activity Database

    Čepica, Stanislav; Bartenschlager, H.; Óvilo, C.; Zrůstová, J.; Masopust, Martin; Fernández, A.; López, A.; Knoll, Aleš; Rohrer, G. A.; Snelling, W. M.; Geldermann, H.

    2010-01-01

    Roč. 41, č. 6 (2010), s. 646-651 ISSN 0268-9146 R&D Projects: GA ČR GA523/07/0353 Institutional research plan: CEZ:AV0Z50450515 Keywords : association study * carcass compositio * genetic mapping Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.203, year: 2010

  4. Perinatal mortality and associated risk factors: a case control study ...

    African Journals Online (AJOL)

    BACKGROUND: Perinatal mortality is reported to be five times higher in developing than in developed nations. Little is known about the commonly associated risk factors for perinatal mortality in Southern Nations National Regional State of Ethiopia. METHODS: A case control study for perinatal mortality was conducted in ...

  5. Genome-wide association study identifies new prostate cancer susceptibility loci

    DEFF Research Database (Denmark)

    Schumacher, Fredrick R.; Berndt, Sonja I.; Siddiq, Afshan

    2011-01-01

    Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have iden...

  6. 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

  7. Genome-wide association study of periweaning failure-to-thrive syndrome (PFTS) in pigs.

    Science.gov (United States)

    Zanella, R; Morés, N; Morés, M A Z; Peixoto, J O; Zanella, E L; Ciacci-Zanella, J R; Ibelli, A M G; Gava, D; Cantão, M E; Ledur, M C

    2016-06-25

    Porcine periweaning-failure-to-thrive syndrome (PFTS) is a condition that affects newly weaned piglets. It is characterised by a progressive debilitation leading to death, in the absence of infectious, nutritional, management or environmental factors. In this study, we present the first report of PFTS in South America and the results of a genome-wide association study to identify the genetic markers associated with the appearance of this condition in a crossbred swine population. Four chromosomal regions were associated with PFTS predisposition, one located on SSCX, one on SSC8, and the two other regions on SSC14. Regions on SSC8 and SSC14 harbour important functional candidate genes involved in human depression and might have an important role in PFTS. Our findings contribute to the increasing knowledge about this syndrome, which has been investigated since 2007, and to the identification of the aetiology of this disease. British Veterinary Association.

  8. VCA-DVC VMware certified associate on vSphere study guide VCAD-510

    CERN Document Server

    Schmidt, Robert

    2015-01-01

    Use this expert guide to prepare for the VCA-DCV exam VCA-DCV VMware Certified Associate on vSphere Study Guide: VCAD-510 is a comprehensive study guide for the VMware Certified Associate - Data Center Virtualization exam. Hands-on examples, real-world scenarios, and expert review questions cover the full exam blueprint, and the companion website offers a suite of tools to help you prepare for the exam including practice exams, electronic flashcards, and a glossary of key terms. In addition, the website includes videos that demonstrate how to complete the more challenging tasks. Focused on p

  9. Cortical Structures Associated With Sports Participation in Children: A Population-Based Study.

    Science.gov (United States)

    López-Vicente, Mónica; Tiemeier, Henning; Wildeboer, Andrea; Muetzel, Ryan L; Verhulst, Frank C; Jaddoe, Vincent W V; Sunyer, Jordi; White, Tonya

    2017-01-01

    We studied cortical morphology in relation to sports participation and type of sport using a large sample of healthy children (n = 911). Sports participation data was collected through a parent-reported questionnaire. Magnetic resonance scans were acquired, and different morphological brain features were quantified. Global volumetric measures were not associated with sports participation. We observed thicker cortex in motor and premotor areas associated with sports participation. In boys, team sports participation, relative to individual sports, was related to thinner cortex in prefrontal brain areas involved in the regulation of behaviors. This study showed a relationship between sports participation and brain maturation.

  10. A Genome-Wide Association Study Reveals Genes Associated with Fusarium Ear Rot Resistance in a Maize Core Diversity Panel

    Science.gov (United States)

    Zila, Charles T.; Samayoa, L. Fernando; Santiago, Rogelio; Butrón, Ana; Holland, James B.

    2013-01-01

    Fusarium ear rot is a common disease of maize that affects food and feed quality globally. Resistance to the disease is highly quantitative, and maize breeders have difficulty incorporating polygenic resistance alleles from unadapted donor sources into elite breeding populations without having a negative impact on agronomic performance. Identification of specific allele variants contributing to improved resistance may be useful to breeders by allowing selection of resistance alleles in coupling phase linkage with favorable agronomic characteristics. We report the results of a genome-wide association study to detect allele variants associated with increased resistance to Fusarium ear rot in a maize core diversity panel of 267 inbred lines evaluated in two sets of environments. We performed association tests with 47,445 single-nucleotide polymorphisms (SNPs) while controlling for background genomic relationships with a mixed model and identified three marker loci significantly associated with disease resistance in at least one subset of environments. Each associated SNP locus had relatively small additive effects on disease resistance (±1.1% on a 0–100% scale), but nevertheless were associated with 3 to 12% of the genotypic variation within or across environment subsets. Two of three identified SNPs colocalized with genes that have been implicated with programmed cell death. An analysis of associated allele frequencies within the major maize subpopulations revealed enrichment for resistance alleles in the tropical/subtropical and popcorn subpopulations compared with other temperate breeding pools. PMID:24048647

  11. 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.

  12. Associations among binge eating behavior patterns and gastrointestinal symptoms: a population-based study

    Science.gov (United States)

    Cremonini, F; Camilleri, M; Clark, MM; Beebe, TJ; Locke, GR; Zinsmeister, AR; Herrick, LM; Talley, NJ

    2009-01-01

    Background The psychological symptoms associated with binge eating disorder (BED) have been well documented. However, the physical symptoms associated with BED have not been explored. Gastrointestinal (GI) symptoms such as heartburn and diarrhea are more prevalent in obese adults, but the associations remain unexplained. Patients with bulimia have increased gastric capacity. The objective of the study was to examine if the severity of binge eating episodes would be associated with upper and lower GI symptoms. Methods Population-based survey of community residents through a mailed questionnaire measuring GI symptoms, frequency of binge eating episodes and physical activity level. The association of GI symptoms with frequency of binge eating episodes was assessed using logistic regression models adjusting for age, gender, body mass index (BMI) and physical activity level. Results In 4096 subjects, BED was present in 6.1%. After adjusting for BMI, age, gender, race, diabetes mellitus, socioeconomic status and physical activity level, BED was independently associated with the following upper GI symptoms: acid regurgitation (P symptoms: diarrhea (P symptoms in the general population, independent of the level of obesity. The relationship between increased GI symptoms and physiological responses to increased volume and calorie loads, nutritional selections and rapidity of food ingestion in individuals with BED deserves further study. PMID:19139750

  13. Association of childhood trauma with cognitive function in healthy adults: a pilot study

    Directory of Open Access Journals (Sweden)

    Lin Jin-Mann S

    2010-07-01

    Full Text Available Abstract Background Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults. Methods In this pilot study, we investigated the relationship between childhood trauma exposure and cognitive function in 47 healthy adults, who were identified as part of a larger study from the general population in Wichita, KS. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB and the Wide-Range-Achievement-Test (WRAT-3 to examine cognitive function and individual achievement. Type and severity of childhood trauma was assessed by the Childhood Trauma Questionnaire (CTQ. Data were analyzed using multiple linear regression on CANTAB measures with primary predictors (CTQ scales and potential confounders (age, sex, education, income. Results Specific CTQ scales were significantly associated with measures of cognitive function. Emotional abuse was associated with impaired spatial working memory performance. Physical neglect correlated with impaired spatial working memory and pattern recognition memory. Sexual abuse and physical neglect were negatively associated with WRAT-3 scores. However, the association did not reach the significance level of p Conclusions Our results suggest that physical neglect and emotional abuse might be associated with memory deficits in adulthood, which in turn might pose a risk factor for the development of psychopathology.

  14. Age at onset in Huntington's disease: replication study on the association of HAP1.

    Science.gov (United States)

    Karadima, Georgia; Dimovasili, Christina; Koutsis, Georgios; Vassilopoulos, Demetris; Panas, Marios

    2012-11-01

    In recent years two association studies investigating the HAP1 T441M (rs4523977) polymorphism as a potential modifying factor of the age at onset (AAO) of Huntington's disease (HD), have been reported. Initially evidence for association was found between the M441 risk allele and the AAO. Subsequently, a second study, although failing to replicate these findings, found evidence for association between the same risk allele and AAO of motor symptoms (mAAO). In the present study, the role of the HAP1 T441M polymorphism as a modifier of the AAO in HD was investigated in a cohort of 298 Greek HD patients. In this cohort the CAG repeat number accounted for 55% of the variance in AAO. No association was found between the HAP1 T441M polymorphism and the AAO of HD. © 2012 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Unique associations among emotion dysregulation dimensions and aggressive tendencies : A multi-site study

    NARCIS (Netherlands)

    Velotti, Patrizia; Casselman, Robert B.; Garofalo, C.; McKenzie, Melissa D.

    2017-01-01

    While problems with emotion regulation (ER) have long been associated with internalizing symptoms, only recently has an ER framework been applied to the study of aggression. Therefore, little is known about the unique and independent associations between specific domains of the ER construct and

  17. Software engineering the mixed model for genome-wide association studies on large samples

    Science.gov (United States)

    Mixed models improve the ability to detect phenotype-genotype associations in the presence of population stratification and multiple levels of relatedness in genome-wide association studies (GWAS), but for large data sets the resource consumption becomes impractical. At the same time, the sample siz...

  18. Poor replication validity of biomedical association studies reported by newspapers.

    Science.gov (United States)

    Dumas-Mallet, Estelle; Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    To investigate the replication validity of biomedical association studies covered by newspapers. We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Journalists preferentially cover initial findings

  19. Poor replication validity of biomedical association studies reported by newspapers.

    Directory of Open Access Journals (Sweden)

    Estelle Dumas-Mallet

    Full Text Available To investigate the replication validity of biomedical association studies covered by newspapers.We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking and a non-lifestyle category (e.g. genetic risk. Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses.Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8% and subsequent (58/600 9.7% lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1% than subsequent ones (45/3718 1.2%. Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48 than subsequent ones (29/45 and than lifestyle studies (31/63. Psychiatric studies covered by newspapers were less often confirmed (10/38 than the neurological (26/41 or somatic (40/77 ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim.Journalists preferentially cover initial findings

  20. Poor replication validity of biomedical association studies reported by newspapers

    Science.gov (United States)

    Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists

  1. Association Study between BDNF Gene Polymorphisms and Autism by Three-Dimensional Gel-Based Microarray

    Directory of Open Access Journals (Sweden)

    Zuhong Lu

    2009-06-01

    Full Text Available Single nucleotide polymorphisms (SNPs are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four SNPs, only C270T polymorphism showed significant differences in the frequency of the allele (χ2 = 7.809, p = 0.005 and genotype (χ2 = 7.800, p = 0.020. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (χ2 = 28.19,p = 3.44e-005. We suggest that BDNF has a possible role in the pathogenesis of autism. The study also show that the polyacrylamide gel-based microarray combined with dual-color hybridization is a rapid, simple and high-throughput method for SNPs genotyping, and can be used for association study of susceptible gene with disorders in large samples.

  2. Genome-Wide Association Study of Psychosis Proneness in the Finnish Population.

    Science.gov (United States)

    Ortega-Alonso, Alfredo; Ekelund, Jesper; Sarin, Antti-Pekka; Miettunen, Jouko; Veijola, Juha; Järvelin, Marjo-Riitta; Hennah, William

    2017-10-21

    The current study examined quantitative measures of psychosis proneness in a nonpsychotic population, in order to elucidate their underlying genetic architecture and to observe if there is any commonality to that already detected in the studies of individuals with overt psychotic conditions, such as schizophrenia and bipolar disorder. Heritability, univariate and multivariate genome-wide association (GWAs) tests, including a series of comprehensive gene-based association analyses, were developed in 4269 nonpsychotic persons participating in the Northern Finland Birth Cohort 1966 study with information on the following psychometric measures: Hypomanic Personality, Perceptual Aberration, Physical and Social Anhedonia (also known as Chapman's Schizotypia scales), and Schizoidia scale. Genome-wide genetic data was available for ~9.84 million SNPs. Heritability estimates ranged from 16% to 27%. Phenotypic, genetic and environmental correlations ranged from 0.04-0.43, 0.25-0.73, and 0.12-0.43, respectively. Univariate GWAs tests revealed an intronic SNP (rs12449097) at the TMC7 gene (16p12.3) that significantly associated (P = 3.485 × 10-8) with the hypomanic scale. Bivariate GWAs tests including the hypomanic and physical anhedonia scales suggested a further borderline significant SNP (rs188320715; P-value = 5.261 × 10-8, ~572 kb downstream the ARID1B gene at 6q25.3). Gene-based tests highlighted 20 additional genes of which 5 had previously been associated to schizophrenia and/or bipolar disorder: CSMD1, CCDC141, SLC1A2, CACNA1C, and SNAP25. Altogether the findings explained from 3.7% to 14.1% of the corresponding trait heritability. In conclusion, this study provides preliminary genomic evidence suggesting that qualitatively similar biological factors may underlie different psychosis proneness measures, some of which could further predispose to schizophrenia and bipolar disorder. © The Author 2017. Published by Oxford University Press on behalf of the Maryland

  3. Associations of salivary cortisol with cognitive function in the Baltimore memory study.

    Science.gov (United States)

    Lee, Brian K; Glass, Thomas A; McAtee, Matthew J; Wand, Gary S; Bandeen-Roche, Karen; Bolla, Karen I; Schwartz, Brian S

    2007-07-01

    The stress responses of the hypothalamic-pituitary-adrenal axis can produce adverse effects on the brain. Previous studies have concluded that an elevated level of cortisol is a risk factor for cognitive dysfunction and decline in aging but have been limited by sex exclusion, restricted cognitive batteries, and small sample sizes. To examine associations among salivary cortisol metrics and cognitive domain scores in an urban adult population. A cross-sectional analysis was conducted using data from a longitudinal study involving 1140 Baltimore, Maryland, residents aged 50 to 70 years. Four salivary cortisol samples were obtained from 967 participants across 1 study visit (before, during, and after cognitive testing as well as at the end of the visit) from which 7 cortisol metrics were created. We examined associations of cortisol metrics with cognitive performance using multiple linear regression. Performance on 20 standard cognitive tests was measured and combined to form summary measures in 7 domains (language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction). Higher levels of pretest and mean cortisol as well as the area under the curve of cortisol over the study visit were associated with worse performance (P executive functioning, verbal memory and learning, and visual memory). For instance, an interquartile range increase in the area under the curve was equivalent to a decrease in the language score expected from an increase in 5.6 (95% confidence interval, 4.2-7.1) years of age. Elevated cortisol was associated with poorer cognitive function across a range of domains in this large population-based study. We believe the findings are consistent with the hypothesis that hypothalamic-pituitary-adrenal axis dysregulation may be a risk factor for poorer cognitive performance in older persons.

  4. The Parahippocampal Cortex Mediates Contextual Associative Memory: Evidence from an fMRI Study

    OpenAIRE

    Li, Mi; Lu, Shengfu; Zhong, Ning

    2016-01-01

    The parahippocampal cortex (PHC) plays a key role in episodic memory, spatial processing, and the encoding of novel stimuli. Recent studies proposed that the PHC is largely involved in contextual associative processing. Consequently, the function of this region has been a hot debate in cognitive neuroscience. To test this assumption, we used two types of experimental materials to form the contextual associative memory: visual objects in reality and meaningless visual shapes. New associations ...

  5. Genome-Wide Association Study of Blood Pressure Traits by Hispanic/Latino Background: the Hispanic Community Health Study/Study of Latinos

    OpenAIRE

    Sofer, Tamar; Wong, Quenna; Hartwig, Fernando P.; Taylor, Kent; Warren, Helen R.; Evangelou, Evangelos; Cabrera, Claudia P.; Levy, Daniel; Kramer, Holly; Lange, Leslie A.; Horta, Bernardo L.; Liang, Jingjing; Le, Thu H.; Edwards, Digna R. Velez; Tayo, Bamidele O.

    2017-01-01

    Hypertension prevalence varies between ethnic groups, possibly due to differences in genetic, environmental, and cultural determinants. Hispanic/Latino Americans are a diverse and understudied population. We performed a genome-wide association study (GWAS) of blood pressure (BP) traits in 12,278 participants from the Hispanics Community Health Study/Study of Latinos (HCHS/SOL). In the discovery phase we identified eight previously unreported BP loci. In the replication stage, we tested these ...

  6. Associations between outdoor temperature and markers of inflammation: a cohort study

    Directory of Open Access Journals (Sweden)

    Zanobetti Antonella

    2010-07-01

    Full Text Available Abstract Background Associations between ambient temperature and cardiovascular mortality are well established. This study investigated whether inflammation could be part of the mechanism leading to temperature-related cardiovascular deaths. Methods The study population consisted of a cohort of 673 men with mean age of 74.6 years, living in the greater Boston area. They were seen for examination roughly every 4 years, and blood samples for inflammation marker analyses were drawn in 2000-2008 (total of 1254 visits. We used a mixed effects model to estimate the associations between ambient temperature and a variety of inflammation markers (C-reactive protein, white blood cell count, soluble Vascular Cell Adhesion Molecule-1, soluble Intercellular Adhesion Molecule-1, tumor necrosis factor alpha, and interleukins -1β, -6 and -8. Random intercept for each subject and several possible confounders, including combustion-related air pollution and ozone, were used in the models. Results We found a 0 to 1 day lagged and up to 4 weeks cumulative responses in C-reactive protein in association with temperature. We observed a 24.9% increase [95% Confidence interval (CI: 7.36, 45.2] in C-reactive protein for a 5°C decrease in the 4 weeks' moving average of temperature. We observed similar associations also between temperature and soluble Intercellular Adhesion Molecule-1 (4.52%, 95% CI: 1.05, 8.10, over 4 weeks' moving average, and between temperature and soluble Vascular Cell Adhesion Molecule-1 (6.60%, 95% CI: 1.31, 12.2 over 4 weeks' moving average. Penalized spline models showed no deviation from linearity. There were no associations between temperature and other inflammation markers. Conclusions Cumulative exposure to decreased temperature is associated with an increase in inflammation marker levels among elderly men. This suggests that inflammation markers are part of intermediate processes, which may lead to cold-, but not heat-, related

  7. 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

  8. Chocolate intake is associated with better cognitive function: The Maine-Syracuse Longitudinal Study.

    Science.gov (United States)

    Crichton, Georgina E; Elias, Merrill F; Alkerwi, Ala'a

    2016-05-01

    Chocolate and cocoa flavanols have been associated with improvements in a range of health complaints dating from ancient times, and has established cardiovascular benefits. Less is known about the effects of chocolate on neurocognition and behaviour. The aim of this study was to investigate whether chocolate intake was associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors. Cross-sectional analyses were undertaken on 968 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intake was related to cognitive performance, measured with an extensive battery of neuropsychological tests. More frequent chocolate consumption was significantly associated with better performance on the Global Composite score, Visual-Spatial Memory and Organization, Working Memory, Scanning and Tracking, Abstract Reasoning, and the Mini-Mental State Examination. With the exception of Working Memory, these relations were not attenuated with statistical control for cardiovascular, lifestyle and dietary factors. Prospective analyses revealed no association between cognitive function and chocolate intake measured up to 18 years later. Further intervention trials and longitudinal studies are needed to explore relations between chocolate, cocoa flavanols and cognition, and the underlying causal mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. American Studies Association — Crossroads of Cultures, Atlanta, Ga., Nov. 11-14, 2004

    OpenAIRE

    Pothier, Jacques

    2006-01-01

    Dans le cadre de son congrès annuel et à l’initiative de sa présidente en exercice, Shelley Fisher Fishkin, l’American Studies Association avait lancé une International Initiative : inviter les représentants de toutes les associations d’études américaines du monde. Parallèlement, American Quarterly, la revue de l’Association, invitait les directeurs des rédactions des revues américanistes.Je représentais donc l’AFEA, la RFEA et Transatlantica.Qu’est-ce que l’American Studies Association ?Le C...

  10. Bipolar disorder and the pseudoautosomal region: An association study

    Energy Technology Data Exchange (ETDEWEB)

    Parsian, A.; Todd, R.D. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1994-03-15

    From family, adoption, and twin studies it is clear that genetic factors play an important role in the etiology of bipolar disorder (McGuffin and Katz: The Biology of Depression, Gaskell, London, 1986). Recently Yoneda et al. reported an association between an allele (A4) of a VNTR marker (DXYS20) for the pseudoautosomal region and bipolar disorder in a Japanese population. In order to test for this association in a Caucasian population, we have typed a sample of 52 subjects with bipolar disorder and 61 normal controls. The bipolar subjects are probands of multiple incidence families. The normal controls are an epidemiologically ascertained sample of middle-aged, unrelated individuals. The two groups were matched for sex and ethnic background. There were no significant differences in the allele or genotype frequencies of DXYS20 between the two groups. In particular, there was no significant difference in the frequency of the A4 allele in normal controls and bipolar patients (0.377 vs. 0.317, respectively). The prevalence of the A4 allele in bipolar patients and normal controls was 0.567 and 0.622, respectively. We were not able to replicate the results of the 1992 Yoneda et al. study. 15 refs., 2 tabs.

  11. Frontotemporal dementia and its subtypes: a genome-wide association study

    Science.gov (United States)

    Ferrari, Raffaele; Hernandez, Dena G; Nalls, Michael A; Rohrer, Jonathan D; Ramasamy, Adaikalavan; Kwok, John B J; Dobson-Stone, Carol; Brooks, William S; Schofield, Peter R; Halliday, Glenda M; Hodges, John R; Piguet, Olivier; Bartley, Lauren; Thompson, Elizabeth; Haan, Eric; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Borroni, Barbara; Padovani, Alessandro; Cruchaga, Carlos; Cairns, Nigel J; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Forloni, Gianluigi; Galimberti, Daniela; Fenoglio, Chiara; Serpente, Maria; Scarpini, Elio; Clarimón, Jordi; Lleó, Alberto; Blesa, Rafael; Waldö, Maria Landqvist; Nilsson, Karin; Nilsson, Christer; Mackenzie, Ian R A; Hsiung, Ging-Yuek R; Mann, David M A; Grafman, Jordan; Morris, Christopher M; Attems, Johannes; Griffiths, Timothy D; McKeith, Ian G; Thomas, Alan J; Pietrini, P; Huey, Edward D; Wassermann, Eric M; Baborie, Atik; Jaros, Evelyn; Tierney, Michael C; Pastor, Pau; Razquin, Cristina; Ortega-Cubero, Sara; Alonso, Elena; Perneczky, Robert; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Kurz, Alexander; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Rogaeva, Ekaterina; George-Hyslop, Peter St; Rossi, Giacomina; Tagliavini, Fabrizio; Giaccone, Giorgio; Rowe, James B; Schlachetzki, J C M; Uphill, James; Collinge, John; Mead, S; Danek, Adrian; Van Deerlin, Vivianna M; Grossman, Murray; Trojanowsk, John Q; van der Zee, Julie; Deschamps, William; Van Langenhove, Tim; Cruts, Marc; Van Broeckhoven, Christine; Cappa, Stefano F; Le Ber, Isabelle; Hannequin, Didier; Golfier, Véronique; Vercelletto, Martine; Brice, Alexis; Nacmias, Benedetta; Sorbi, Sandro; Bagnoli, Silvia; Piaceri, Irene; Nielsen, Jørgen E; Hjermind, Lena E; Riemenschneider, Matthias; Mayhaus, Manuel; Ibach, Bernd; Gasparoni, Gilles; Pichler, Sabrina; Gu, Wei; Rossor, Martin N; Fox, Nick C; Warren, Jason D; Spillantini, Maria Grazia; Morris, Huw R; Rizzu, Patrizia; Heutink, Peter; Snowden, Julie S; Rollinson, Sara; Richardson, Anna; Gerhard, Alexander; Bruni, Amalia C; Maletta, Raffaele; Frangipane, Francesca; Cupidi, Chiara; Bernardi, Livia; Anfossi, Maria; Gallo, Maura; Conidi, Maria Elena; Smirne, Nicoletta; Rademakers, Rosa; Baker, Matt; Dickson, Dennis W; Graff-Radford, Neill R; Petersen, Ronald C; Knopman, David; Josephs, Keith A; Boeve, Bradley F; Parisi, Joseph E; Seeley, William W; Miller, Bruce L; Karydas, Anna M; Rosen, Howard; van Swieten, John C; Dopper, Elise G P; Seelaar, Harro; Pijnenburg, Yolande AL; Scheltens, Philip; Logroscino, Giancarlo; Capozzo, Rosa; Novelli, Valeria; Puca, Annibale A; Franceschi, M; Postiglione, Alfredo; Milan, Graziella; Sorrentino, Paolo; Kristiansen, Mark; Chiang, Huei-Hsin; Graff, Caroline; Pasquier, Florence; Rollin, Adeline; Deramecourt, Vincent; Lebert, Florence; Kapogiannis, Dimitrios; Ferrucci, Luigi; Pickering-Brown, Stuart; Singleton, Andrew B; Hardy, John; Momeni, Parastoo

    2014-01-01

    Summary Background Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. All participants had European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) and suggestive single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8) that encompassed the HLA locus at 6p21.3 in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC, for the behavioural FTD subtype. Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation incis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and possibly to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of

  12. 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.

  13. Testing for direct genetic effects using a screening step in family-based association studies

    Directory of Open Access Journals (Sweden)

    Sharon M Lutz

    2013-11-01

    Full Text Available In genome wide association studies (GWAS, families based studies tend to have less power to detect genetic associations than population based studies, such as case-control studies. This can be an issue when testing if genes in a family based GWAS have a direct effect on the phenotype of interest or if the genes act indirectly through a secondary phenotype. When multiple SNPs are tested for a direct effect in the family based study, a screening step can be used to minimize the burden of multiple comparisons in the causal analysis. We propose a 2-stage screening step that can be incorporated into the family based association test (FBAT approach similar to the conditional mean model approach in the VanSteen-algorithm [1]. Simulations demonstrate that the type 1 error is preserved and this method is advantageous when multiple markers are tested. This method is illustrated by an application to the Framingham Heart Study.

  14. Pseudoexfoliation: normative data and associations. The Central India Eye and Medical Study.

    Directory of Open Access Journals (Sweden)

    Jost B Jonas

    Full Text Available PURPOSE: To assess the prevalence of pseudoexfoliation (PEX and its associations in a population-based setting. DESIGN: Population-based, cross-sectional study. METHODS: The Central India Eye and Medical Study included 4711 individuals. All study participants underwent a detailed ophthalmological examination. After medical pupil dilation, PEX was assessed by an experienced ophthalmologist using slit-lamp based biomicroscopy. RESULTS: Slit lamp examination results were available for 4646 (98.6% study participants with a mean age of 49.3 ± 13.3 years (range: 30-100 years. PEX was detected in 87 eyes (prevalence: 0.95 ± 0.10% (95%CI: 0.75, 1.15 of 69 subjects (prevalence: 1.49 ± 0.18% (95%CI: 1.14, 1.83. PEX prevalence increased significantly (P<0.001 from 0% in the age group of 30-39 years, to 2.85 ± 0.56% in the age group of 60-69 years, to 6.60 ± 1.21% in the age group of 70-79 years, and to 12.3 ± 4.11% in the age group of 80+ years. In multivariate analysis, PEX prevalence was associated with higher age (P<0.001; regression coefficient B:0.11; odds ratio (OR: 1.11 (95%CI: 1.09, 1.13, lower body mass index (P = 0.001; B: -0.12; OR: 0.88 (95CI: 0.82, 0.95 and higher diastolic blood pressure (P = 0.002; B: 0.02; OR: 1.03 (95%CI: 1.01, 1.04. In the multivariate analysis, PEX was not associated with retinal nerve fiber layer cross section area (P = 0.76 and presence of open-angle glaucoma (P = 0.15. CONCLUSIONS: In a rural Central Indian population aged 30+ years, PEX prevalence (mean: 1.49 ± 0.18% was significantly associated with older age, lower body mass index and higher diastolic blood pressure. It was not significantly associated with optic nerve head measurements, refractive error, any ocular biometric parameter, nuclear cataract, early age-related macular degeneration and retinal vein occlusion, diabetes mellitus, smoking, and dyslipidemia.

  15. 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...

  16. Epigenome-wide association studies without the need for cell-type composition.

    Science.gov (United States)

    Zou, James; Lippert, Christoph; Heckerman, David; Aryee, Martin; Listgarten, Jennifer

    2014-03-01

    In epigenome-wide association studies, cell-type composition often differs between cases and controls, yielding associations that simply tag cell type rather than reveal fundamental biology. Current solutions require actual or estimated cell-type composition--information not easily obtainable for many samples of interest. We propose a method, FaST-LMM-EWASher, that automatically corrects for cell-type composition without the need for explicit knowledge of it, and then validate our method by comparison with the state-of-the-art approach. Corresponding software is available from http://www.microsoft.com/science/.

  17. Non-steroidal anti-inflammatory drugs use is associated with reduced risk of inflammation-associated cancers: NIH-AARP study.

    Directory of Open Access Journals (Sweden)

    Fatma M Shebl

    Full Text Available Chronic inflammation has been linked to cancers, and use of non-steroidal anti-inflammatory drugs (NSAIDs has been associated with reduced risk of several cancers. To further refine the magnitude of NSAID-related associations, in particular for cancers related to inflammation, such as alcohol-, infection-, obesity-, and smoking-related cancers, as well as for less common cancers, we evaluated the use of NSAIDs and cancer risk in a very large cohort. We used propensity scores to account for potential selection bias and hypothesized that NSAID use is associated with decreased cancer incidence.We conducted a prospective study among 314,522 participants in the NIH-AARP Diet and Health Study. Individuals who completed the lifestyle questionnaire, which included NSAID use, in 1996-1997 were followed through 2006. Information on cancer incidence was ascertained by linking to cancer registries and vital status databases.During 2,715,994 person-years of follow-up (median 10.1 person-years, there were 51,894 incident cancers. Compared with non-users of NSAIDs, individuals who reported use in the 12 months prior to interview had a significantly lower risk of all inflammation-related cancer, alcohol-related, infection-related, obesity-related, and smoking-related cancers [hazard ratio (HR (95% CI 0.90 (0.87-0.93, 0.80 (0.74-0.85, 0.82 (0.78-0.87, 0.88 (0.84-0.92, and 0.88 (0.85-0.92 respectively].After accounting for potential selection bias, our data showed an inverse association between NSAID use and alcohol-related, infection-related, obesity-related, and smoking-related cancers and support the hypothesis that inflammation is related to an increased risk of certain cancers.

  18. Trick or treat: The effect of placebo on the power of pharmacogenetic association studies

    Directory of Open Access Journals (Sweden)

    Singer Clara

    2005-03-01

    Full Text Available Abstract The genetic mapping of drug-response traits is often characterised by a poor signal-to-noise ratio that is placebo related and which distinguishes pharmacogenetic association studies from classical case-control studies for disease susceptibility. The goal of this study was to evaluate the statistical power of candidate gene association studies under different pharmacogenetic scenarios, with special emphasis on the placebo effect. Genotype/phenotype data were simulated, mimicking samples from clinical trials, and response to the drug was modelled as a binary trait. Association was evaluated by a logistic regression model. Statistical power was estimated as a function of the number of single nucleotide polymorphisms (SNPs genotyped, the frequency of the placebo 'response', the genotype relative risk (GRR of the response polymorphism, the strategy for selecting SNPs for genotyping, the number of individuals in the trial and the ratio of placebo-treated to drugtreated patients. We show that: (i the placebo 'response' strongly affects the statistical power of association studies -- even a highly penetrant drug-response allele requires at least a 500-patient trial in order to reach 80 per cent power, several-fold more than the value estimated by standard tools that are not calibrated to pharmacogenetics; (ii the power of a pharmacogenetic association study depends primarily on the penetrance of the response genotype and, when this penetrance is fixed, power decreases for larger placebo effects; (iii power is dramatically increased when adding markers; (iv an optimal study design includes a similar number of placebo- and drugtreated patients; and (v in this setting, straightforward haplotype analysis does not seem to have an advantage over single marker analysis.

  19. Mortality from Respiratory Diseases Associated with Opium Use – A Population Based Cohort Study

    Science.gov (United States)

    Rahmati, Atieh; Shakeri, Ramin; Khademi, Hooman; Poustchi, Hossein; Pourshams, Akram; Etemadi, Arash; Khoshnia, Masoud; Sohrabpour, Amir Ali; Aliasgari, Ali; Jafari, Elham; Islami, Farhad; Semnani, Shahryar; Gharavi, Samad; Abnet, Christian C.; Pharoah, Paul DP; Brennan, Paul; Boffetta, Paolo; Dawsey, Sanford M.; Malekzadeh, Reza; Kamangar, Farin

    2018-01-01

    Background Recent studies have suggested that opium use may increase mortality from cancer and cardiovascular diseases. However, no comprehensive study of opium use and mortality from respiratory diseases has been published. We aimed to study the association between opium use and mortality from respiratory disease using prospectively collected data. Methods We used data from the Golestan Cohort Study (GCS), a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50,045 adults were enrolled from 2004 to 2008, and followed annually until June 2015, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest. Results During the follow-up period 331 deaths from respiratory disease were reported (85 due to respiratory malignancies and 246 due to nonmalignant etiologies). Opium use was associated with an increased risk of death from any respiratory disease (adjusted hazard ratio (HR) 95% CI; 3.13 (2.42-4.04)). The association was dose-dependent with a HR of 3.84 (2.61-5.67) for the highest quintile of cumulative opium use vs. never use (Ptrendopium use and malignant and nonmalignant causes of respiratory mortality were 1.96 (1.18-3.25) and 3.71 (2.76-4.96), respectively. Conclusion Long-term opium use is associated with increased mortality from both malignant and nonmalignant respiratory diseases. PMID:27885167

  20. Bruxism Is Associated With Nicotine Dependence: A Nationwide Finnish Twin Cohort Study

    Science.gov (United States)

    Ahlberg, J.; Hublin, C.; Broms, U.; Madden, P. A. F.; Könönen, M.; Koskenvuo, M.; Lobbezoo, F.; Kaprio, J.

    2010-01-01

    Objectives: To investigate the association of smoking with bruxism while controlling for genetic and environmental factors using a co-twin-control design. Especially, the role of nicotine dependence was studied in this context. Methods: The material derives from the Finnish Twin Cohort consisting of 12,502 twin individuals who responded to a questionnaire in 1990 (response rate of 77%). All were born in 1930–1957, the mean age being 44 years. The questionnaire covered 103 multiple choice questions, 7 dealing with tobacco use and 22 with sleep and vigilance matters, including perceived bruxism. In addition, a subsample derived from the Nicotine Addiction Genetics Finland Study containing 445 twin individuals was studied. Results: In age- and gender-controlled multinomial logistic regression, both monthly and rarely reported bruxism associated with both current cigarette smoking (odds ratio [OR] = 1.74 and 1.64) and former cigarette smoking (OR = 1.64 and 1.47). Weekly bruxism associated with current smoking (OR = 2.85). Current smokers smoking 20 or more cigarettes a day reported weekly bruxism more likely (OR = 1.61–1.97) than those smoking less. Among twin pairs (N = 142) in which one twin was a weekly bruxer and the cotwin a never bruxer, there were 13 monozygotic pairs in which one twin was a current smoker and the other twin was not. In all cases, the bruxer was the smoker (p = .0003). Nicotine dependence associated significantly with bruxism. Conclusions: Our twin study provides novel evidence for a possible causal link between tobacco use and bruxism among middle-aged adults. Nicotine dependence may be a significant predisposing factor for bruxism. PMID:21041838

  1. Weighting sequence variants based on their annotation increases power of whole-genome association studies

    DEFF Research Database (Denmark)

    Sveinbjornsson, Gardar; Albrechtsen, Anders; Zink, Florian

    2016-01-01

    The consensus approach to genome-wide association studies (GWAS) has been to assign equal prior probability of association to all sequence variants tested. However, some sequence variants, such as loss-of-function and missense variants, are more likely than others to affect protein function...... for the family-wise error rate (FWER), using as weights the enrichment of sequence annotations among association signals. We show that this weighted adjustment increases the power to detect association over the standard Bonferroni correction. We use the enrichment of associations by sequence annotation we have...

  2. Motivational profiles of medical students: association with study effort, academic performance and exhaustion.

    Science.gov (United States)

    Kusurkar, Rashmi A; Croiset, Gerda; Galindo-Garré, Francisca; Ten Cate, Olle

    2013-06-19

    Students enter the medical study with internally generated motives like genuine interest (intrinsic motivation) and/or externally generated motives like parental pressure or desire for status or prestige (controlled motivation). According to Self-determination theory (SDT), students could differ in their study effort, academic performance and adjustment to the study depending on the endorsement of intrinsic motivation versus controlled motivation. The objectives of this study were to generate motivational profiles of medical students using combinations of high or low intrinsic and controlled motivation and test whether different motivational profiles are associated with different study outcomes. Participating students (N = 844) from University Medical Center Utrecht, the Netherlands, were classified to different subgroups through K-means cluster analysis using intrinsic and controlled motivation scores. Cluster membership was used as an independent variable to assess differences in study strategies, self-study hours, academic performance and exhaustion from study. Four clusters were obtained: High Intrinsic High Controlled (HIHC), Low Intrinsic High Controlled (LIHC), High Intrinsic Low Controlled (HILC), and Low Intrinsic Low Controlled (LILC). HIHC profile, including the students who are interest + status motivated, constituted 25.2% of the population (N = 213). HILC profile, including interest-motivated students, constituted 26.1% of the population (N = 220). LIHC profile, including status-motivated students, constituted 31.8% of the population (N = 268). LILC profile, including students who have a low-motivation and are neither interest nor status motivated, constituted 16.9% of the population (N = 143). Interest-motivated students (HILC) had significantly more deep study strategy (p motivated (LIHC) and low-motivation (LILC) students. The interest-motivated profile of medical students (HILC) is associated with good study hours, deep

  3. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  4. Association of Genetic Risk for Schizophrenia With Nonparticipation Over Time in a Population-Based Cohort Study.

    Science.gov (United States)

    Martin, Joanna; Tilling, Kate; Hubbard, Leon; Stergiakouli, Evie; Thapar, Anita; Davey Smith, George; O'Donovan, Michael C; Zammit, Stanley

    2016-06-15

    Progress has recently been made in understanding the genetic basis of schizophrenia and other psychiatric disorders. Longitudinal studies are complicated by participant dropout, which could be related to the presence of psychiatric problems and associated genetic risk. We tested whether common genetic variants implicated in schizophrenia were associated with study nonparticipation among 7,867 children and 7,850 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC; 1991-2007), a longitudinal population cohort study. Higher polygenic risk scores for schizophrenia were consistently associated with noncompletion of questionnaires by study mothers and children and nonattendance at data collection throughout childhood and adolescence (ages 1-15 years). These associations persisted after adjustment for other potential correlates of nonparticipation. Results suggest that persons at higher genetic risk for schizophrenia are likely to be underrepresented in cohort studies, which will underestimate risk of this and related psychiatric, cognitive, and behavioral phenotypes in the population. Statistical power to detect associations with these phenotypes will be reduced, while analyses of schizophrenia-related phenotypes as outcomes may be biased by the nonrandom missingness of these phenotypes, even if multiple imputation is used. Similarly, in complete-case analyses, collider bias may affect associations between genetic risk and other factors associated with missingness. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

  5. Service Journalism in the Association Magazine: A Case Study of the "Angus Journal."

    Science.gov (United States)

    Jeffers, Dennis W.

    Examining the role of service journalism in association magazines (magazines focusing on technical and educational information relating to specific practices of association members), a case study of the "Angus Journal" (a monthly magazine devoted to the beef breeding industry) investigated the problem of determining the amount of service…

  6. 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…

  7. A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Chiò, Adriano; Schymick, Jennifer C; Restagno, Gabriella; Scholz, Sonja W; Lombardo, Federica; Lai, Shiao-Lin; Mora, Gabriele; Fung, Hon-Chung; Britton, Angela; Arepalli, Sampath; Gibbs, J Raphael; Nalls, Michael; Berger, Stephen; Kwee, Lydia Coulter; Oddone, Eugene Z; Ding, Jinhui; Crews, Cynthia; Rafferty, Ian; Washecka, Nicole; Hernandez, Dena; Ferrucci, Luigi; Bandinelli, Stefania; Guralnik, Jack; Macciardi, Fabio; Torri, Federica; Lupoli, Sara; Chanock, Stephen J; Thomas, Gilles; Hunter, David J; Gieger, Christian; Wichmann, H Erich; Calvo, Andrea; Mutani, Roberto; Battistini, Stefania; Giannini, Fabio; Caponnetto, Claudia; Mancardi, Giovanni Luigi; La Bella, Vincenzo; Valentino, Francesca; Monsurrò, Maria Rosaria; Tedeschi, Gioacchino; Marinou, Kalliopi; Sabatelli, Mario; Conte, Amelia; Mandrioli, Jessica; Sola, Patrizia; Salvi, Fabrizio; Bartolomei, Ilaria; Siciliano, Gabriele; Carlesi, Cecilia; Orrell, Richard W; Talbot, Kevin; Simmons, Zachary; Connor, James; Pioro, Erik P; Dunkley, Travis; Stephan, Dietrich A; Kasperaviciute, Dalia; Fisher, Elizabeth M; Jabonka, Sibylle; Sendtner, Michael; Beck, Marcus; Bruijn, Lucie; Rothstein, Jeffrey; Schmidt, Silke; Singleton, Andrew; Hardy, John; Traynor, Bryan J

    2009-04-15

    The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors.

  8. Occupational lifting is associated with hip osteoarthritis: a Japanese case-control study.

    Science.gov (United States)

    Yoshimura, N; Sasaki, S; Iwasaki, K; Danjoh, S; Kinoshita, H; Yasuda, T; Tamaki, T; Hashimoto, T; Kellingray, S; Croft, P; Coggon, D; Cooper, C

    2000-02-01

    Hip osteoarthritis (OA) is a frequent cause of pain and disability in Western countries, but the disorder is less common in Japan. A case-control study in Britain found obesity, hip injury, and occupational lifting to be associated with hip OA among men and women. However, there are few epidemiological studies concerning factors associated with hip OA in Japan. We performed a comparable case-control study of the disorder in Japan, and contrasted the findings with those from Britain. The study was carried out in 2 health districts in Wakayama Prefecture, Japan. Cases were men and women aged > or = 45 years listed for total hip arthroplasty due to OA over one year, and who did not have an established cause of secondary OA (e.g., rheumatoid arthritis, ankylosing spondylitis). For each case, a control was selected randomly from the general population and was individually matched to the case for age, sex, and district of residence. Cases and controls were interviewed with a structured questionnaire about medical history, physical activity, socioeconomic factors, and occupation. Measurements were made of height and weight. One hundred fourteen cases (103 women, 11 men) were compared with 114 controls. We found no relationship between obesity and hip OA (OR = 1.0, 95% CI 0.5-1.9; highest vs lowest thirds of distribution of body mass index). There was, however, a statistically significant association between occupational lifting and hip OA, such that regular lifting of 25 kg in the individual's first job (OR = 3.6, 95% CI 1.3-9.7) or of 50 kg in their main job (OR = 4.0, 95% CI 1.1-14.2) was associated with increased risk of hip OA. These associations remained after adjustment for potential confounding variables. In contrast, those subjects who spent > 2 h each day sitting during their first job were significantly less likely to have the disorder (crude OR = 0.5, 95% CI 0.3-0.9). This association also remained statistically significant after adjustment for potential risk

  9. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population.

    Science.gov (United States)

    Palomba, Grazia; Loi, Angela; Porcu, Eleonora; Cossu, Antonio; Zara, Ilenia; Budroni, Mario; Dei, Mariano; Lai, Sandra; Mulas, Antonella; Olmeo, Nina; Ionta, Maria Teresa; Atzori, Francesco; Cuccuru, Gianmauro; Pitzalis, Maristella; Zoledziewska, Magdalena; Olla, Nazario; Lovicu, Mario; Pisano, Marina; Abecasis, Gonçalo R; Uda, Manuela; Tanda, Francesco; Michailidou, Kyriaki; Easton, Douglas F; Chanock, Stephen J; Hoover, Robert N; Hunter, David J; Schlessinger, David; Sanna, Serena; Crisponi, Laura; Palmieri, Giuseppe

    2015-05-10

    Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p <  0(-6) level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16 x 10(-5)), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population.

  10. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population

    International Nuclear Information System (INIS)

    Palomba, Grazia; Loi, Angela; Porcu, Eleonora; Cossu, Antonio; Zara, Ilenia

    2015-01-01

    Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 10 −6 level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10 −5 , we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16x10 −5 ), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population. The online version of this article (doi:10.1186/s12885-015-1392-9) contains supplementary material, which is available to authorized users

  11. Ischemic stroke is associated with the ABO locus: the EuroCLOT study.

    OpenAIRE

    Williams, F.M.; Carter, A.M.; Hysi, P.G.; Surdulescu, G.; Hodgkiss, D.; Soranzo, N.; Traylor, M.; Bevan, S.; Dichgans, M.; Rothwell, P.M.; Sudlow, C.; Farrall, M.; Silander, K.; Kaunisto, M.; Wagner, P.

    2013-01-01

    OBJECTIVE: End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy volunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype.METHODS: Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stag...

  12. 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

  13. 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.

  14. Chelsea, Pimlico and Belgravia District Nursing Association 1930-1939: A case study.

    Science.gov (United States)

    Bliss, Julie

    2017-07-02

    The case study explores how the expansion of the health services during the interwar period impacted upon the status of district nursing and examines how being a voluntary service shaped district nursing associations. A range of primary sources were used; the Association Annual Reports, the Medical Officer for Health Annual Reports for the Borough of Chelsea, the Ministry of Health records, the archives of the Queen's Nursing Institute (QNI) and the Borough of Chelsea Council Minutes. The Medical Officer for Health Reports and the Council minutes identify efforts to improve environmental factors that impacted upon health. These primary sources briefly note the contribution of the Association suggesting that it was integral to the health care provision but considered a constant. The impact of changes to the 1932 Sunday Entertainments Act provide an interesting juxtaposition between the acknowledged value of district nursing and the constant struggle to fundraise in order to provide home nursing. Throughout the 1930s the Association experienced staff shortages and challenges regarding recruitment. The complexities of payment for municipal health services following the 1929 Local Government Act contributed to the staffing challenges. The move to a block grant in 1938 provided increased stability with regards to income. The case study identifies a contradiction regarding the esteem and value placed upon district nursing associations providing home nursing and the constant challenge of resources. District nursing services face similar challenges and this is the 130 th anniversary of the Queen's Nursing Institute.

  15. A genome-wide association study identifies candidate loci associated to syringomyelia secondary to Chiari-like malformation in Cavalier King Charles Spaniels.

    Science.gov (United States)

    Ancot, Frédéric; Lemay, Philippe; Knowler, Susan P; Kennedy, Karen; Griffiths, Sandra; Cherubini, Giunio Bruto; Sykes, Jane; Mandigers, Paul J J; Rouleau, Guy A; Rusbridge, Clare; Kibar, Zoha

    2018-03-22

    Syringomyelia (SM) is a common condition affecting brachycephalic toy breed dogs and is characterized by the development of fluid-filled cavities within the spinal cord. It is often concurrent with a complex developmental malformation of the skull and craniocervical vertebrae called Chiari-like malformation (CM) characterized by a conformational change and overcrowding of the brain and cervical spinal cord particularly at the craniocervical junction. CM and SM have a polygenic mode of inheritance with variable penetrance. We identified six cranial T1-weighted sagittal MRI measurements that were associated to maximum transverse diameter of the syrinx cavity. Increased syrinx transverse diameter has been correlated previously with increased likelihood of behavioral signs of pain. We next conducted a whole genome association study of these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32 with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be significantly associated to two traits associated with a reduced volume and altered orientation of the caudal cranial fossa. Their reconstructed haplotypes defined two associated regions that harbor only two genes: PCDH17 on CFA22 and ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically in the brain and spinal cord. ZWINT plays a role in chromosome segregation and its expression is increased with the onset of neuropathic pain. Targeted genomic sequencing of these regions identified respectively 37 and 339 SNPs with significantly associated P values. Genotyping of tagSNPs selected from these 2 candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM affected) identified 2 SNPs on CFA22 that were significantly associated to SM strengthening the candidacy of this locus in SM development. We identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and ZWINT, significantly associated to two traits associated with syrinx transverse

  16. Associations Between Antiretroviral Treatment and Avascular Bone Necrosis: The Swiss HIV Cohort Study

    Science.gov (United States)

    Bayard, Cornelia; Ledergerber, Bruno; Flepp, Markus; Lecompte, Thanh; Moulin, Estelle; Hoffmann, Matthias; Weber, Rainer; Staehelin, Cornelia; Di Benedetto, Caroline; Fux, Christoph A; Tarr, Philip E; Aubert, V; Battegay, M; Bernasconi, E; Böni, J; Braun, DL; Bucher, HC; Calmy, A; Cavassini, M; Ciuffi, A; Dollenmaier, G; Egger, M; Elzi, L; Fehr, J; Fellay, J; Furrer, H; Fux, CA; Günthard, HF; Haerry, D; Hasse, B; Hirsch, HH; Hoffmann, M; Hösli, I; Kahlert, C; Kaiser, L; Keiser, O; Klimkait, T; Kouyos, RD; Kovari, H; Ledergerber, B; Martinetti, G; Martinez de Tejada, B; Marzolini, C; Metzner, KJ; Müller, N; Nicca, D; Pantaleo, G; Paioni, P; Rauch, A; Rudin, C; Scherrer, AU; Schmid, P; Speck, R; Stöckle, M; Tarr, P; Trkola, A; Vernazza, P; Wandeler, G; Weber, R; Yerly, S

    2017-01-01

    Abstract Background HIV-infected individuals have an increased risk of avascular bone necrosis (AVN). Antiretroviral therapy (ART) and particularly protease inhibitors (PI) have been implicated as a risk factor. We aimed to study the associations of ART with the occurrence of AVN among Swiss HIV Cohort Study participants (SHCS). Methods We used incidence density sampling to perform a case control study within the Swiss HIV Cohort Study (SHCS) comparing prospectively collected AVN cases and controls by conditional logistic regression analysis. To evaluate the effect of ART, multivariable models were adjusted for HIV transmission risk group, age, alcohol consumption, use of corticosteroids, CD4 nadir, maximum viral load, and pancreatitis. Results We compared 74 AVN cases and 145 controls. Associations with AVN were shown for heterosexual HIV acquisition (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1–10), alcohol consumption (OR, 2.7; 95% CI, 1.3–5.7), and hyperlipidemia (OR, 3.6; 95% CI, 1.4–9.6). After adding ART substances to the multivariable base model, there was evidence of an association for treatment with tenofovir (TDF) >1 year (OR, 4.4; 95% CI, 1.4–14) with AVN. Neither exposure to specific frequently prescribed ART combinations or ART drug classes nor cumulative ART exposure showed any associations with AVN. Conclusions In the HIV-infected population, a combination of risk factors such as heterosexual HIV acquisition, moderate to severe alcohol intake, and hyperlipidemia seem to contribute to AVN. ART does not seem to be a relevant risk factor for AVN. The association of prolonged TDF exposure with AVN needs to be confirmed. PMID:29026869

  17. Association of UV radiation with Parkinson disease incidence: A nationwide French ecologic study

    Energy Technology Data Exchange (ETDEWEB)

    Kravietz, Adam [University of Miami Miller School of Medicine, Miami, Florida (United States); Kab, Sofiane [Santé publique France, Direction santé travail, F-94415 Saint-Maurice (France); CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805 Villejuif (France); Wald, Lucien [MINES ParisTech, PSL Research University, Sophia Antipolis (France); Dugravot, Aline [CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805 Villejuif (France); Singh-Manoux, Archana [CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805 Villejuif (France); Department of Epidemiology and Public Health, University College London, London (United Kingdom); Moisan, Frédéric [Santé publique France, Direction santé travail, F-94415 Saint-Maurice (France); Elbaz, Alexis, E-mail: alexis.elbaz@inserm.fr [Santé publique France, Direction santé travail, F-94415 Saint-Maurice (France); CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805 Villejuif (France)

    2017-04-15

    Background: Vitamin D is thought to contribute to brain health, but it is unclear whether low vitamin D levels are associated with increased incidence of Parkinson's disease (PD). Using ultraviolet B (UV-B) as a surrogate for vitamin D levels, we conducted a nationwide ecologic study in France in order to examine the association of UV-B with PD incidence. Methods: We used French national drug claims databases to identify PD cases using a validated algorithm. UV-B data from the solar radiation database were derived from satellite images. We estimated PD incidence (2010–2012) at the canton level (small administrative French unit) and used multilevel Poisson regression to examine its association with UV-B (2005 annual average), after adjustment for age, sex, deprivation index, density of neurologists, smoking, proportion of agricultural land, and vitamin D supplementation. Results: Analyses are based on 69,010 incident PD patients. The association between UV-B and PD incidence was quadratic (P<0.001) and modified by age (P<0.001). Below 70y, incidence was higher in the bottom quintile (relative risk, RR{sub Q1:45-49y}=1.18, 95% CI=1.08–1.29) compared with the middle UV-B quintile, and lower in the top quintile (RR{sub Q5:45-49y}=0.85 [0.77–0.94]). An opposite pattern was observed in older subjects (RR{sub Q1:85-89y}=0.92 [0.89–0.96]; RR{sub Q5:85-89y}=1.06 [1.02–1.11]). Analysis based on continuous UV-B yielded similar conclusions. Conclusions: In this nationwide study, there was an age-dependent quadratic association between UV-B and PD incidence. This study suggests that reasonable UV-B exposure is associated with lower PD risk in younger persons and that future studies should examine dose-response relations and take age into account. - Highlights: • There is an age-dependent quadratic association between UV-B and PD incidence. • Reasonable UV-B exposure is beneficial in younger persons for the risk of PD. • Our findings are consistent with a

  18. 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

  19. New Sequence Variants in HLA Class II/III Region Associated with Susceptibility to Knee Osteoarthritis Identified by Genome-Wide Association Study

    Science.gov (United States)

    Nakajima, Masahiro; Takahashi, Atsushi; Kou, Ikuyo; Rodriguez-Fontenla, Cristina; Gomez-Reino, Juan J.; Furuichi, Tatsuya; Dai, Jin; Sudo, Akihiro; Uchida, Atsumasa; Fukui, Naoshi; Kubo, Michiaki; Kamatani, Naoyuki; Tsunoda, Tatsuhiko; Malizos, Konstantinos N.; Tsezou, Aspasia; Gonzalez, Antonio; Nakamura, Yusuke; Ikegawa, Shiro

    2010-01-01

    Osteoarthritis (OA) is a common disease that has a definite genetic component. Only a few OA susceptibility genes that have definite functional evidence and replication of association have been reported, however. Through a genome-wide association study and a replication using a total of ∼4,800 Japanese subjects, we identified two single nucleotide polymorphisms (SNPs) (rs7775228 and rs10947262) associated with susceptibility to knee OA. The two SNPs were in a region containing HLA class II/III genes and their association reached genome-wide significance (combined P = 2.43×10−8 for rs7775228 and 6.73×10−8 for rs10947262). Our results suggest that immunologic mechanism is implicated in the etiology of OA. PMID:20305777

  20. 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

  1. Mortality Associated with Severe Sepsis Among Age-Similar Women with and without Pregnancy-Associated Hospitalization in Texas: A Population-Based Study.

    Science.gov (United States)

    Oud, Lavi

    2016-06-10

    BACKGROUND The reported mortality among women with pregnancy-associated severe sepsis (PASS) has been considerably lower than among severely septic patients in the general population, with the difference being attributed to the younger age and lack of chronic illness among the women with PASS. However, no comparative studies were reported to date between patients with PASS and age-similar women with severe sepsis not associated with pregnancy (NPSS). MATERIAL AND METHODS We used the Texas Inpatient Public Use Data File to compare the crude and adjusted hospital mortality between women with severe sepsis, aged 20-34 years, with and without pregnancy-associated hospitalizations during 2001-2010, following exclusion of those with reported chronic comorbidities, as well as alcohol and drug abuse. RESULTS Crude hospital mortality among PASS vs. NPSS hospitalizations was lower for the whole cohort (6.7% vs. 14.1% [p<0.0001]) and those with ≥3 organ failures (17.6% vs. 33.2% [p=0.0100]). Adjusted PASS mortality (odds ratio [95% CI]) was 0.57 (0.38-0.86) [p=0.0070]. CONCLUSIONS Hospital mortality was unexpectedly markedly and consistently lower among women with severe sepsis associated with pregnancy, as compared with contemporaneous, age-similar women with severe sepsis not associated with pregnancy, without reported chronic comorbidities. Further studies are warranted to examine the sources of the observed differences and to corroborate our findings.

  2. Post-genome wide association studies and functional analyses identify association of MPP7 gene variants with site-specific bone mineral density.

    Science.gov (United States)

    Xiao, Su-Mei; Kung, Annie Wai Chee; Gao, Yi; Lau, Kam-Shing; Ma, Alvin; Zhang, Zhen-Lin; Liu, Jian-Min; Xia, Wiebo; He, Jin-Wei; Zhao, Lin; Nie, Min; Fu, Wei-Zhen; Zhang, Min-Jia; Sun, Jing; Kwan, Johnny S H; Tso, Gloria Hoi Wan; Dai, Zhi-Jie; Cheung, Ching-Lung; Bow, Cora H; Leung, Anskar Yu Hung; Tan, Kathryn Choon Beng; Sham, Pak Chung

    2012-04-01

    Our previous genome-wide association study (GWAS) in a Hong Kong Southern Chinese population with extreme bone mineral density (BMD) scores revealed suggestive association with MPP7, which ranked second after JAG1 as a candidate gene for BMD. To follow-up this suggestive signal, we replicated the top single-nucleotide polymorphism rs4317882 of MPP7 in three additional independent Asian-descent samples (n= 2684). The association of rs4317882 reached the genome-wide significance in the meta-analysis of all available subjects (P(meta)= 4.58 × 10(-8), n= 4204). Site heterogeneity was observed, with a larger effect on spine than hip BMD. Further functional studies in a zebrafish model revealed that vertebral bone mass was lower in an mpp7 knock-down model compared with the wide-type (P= 9.64 × 10(-4), n= 21). In addition, MPP7 was found to have constitutive expression in human bone-derived cells during osteogenesis. Immunostaining of murine MC3T3-E1 cells revealed that the Mpp7 protein is localized in the plasma membrane and intracytoplasmic compartment of osteoblasts. In an assessment of the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of transcriptional factor GATA2 to the risk allele 'A' but not the 'G' allele of rs4317882. An mRNA expression study in human peripheral blood mononuclear cells confirmed that the low BMD-related allele 'A' of rs4317882 was associated with lower MPP7 expression (P= 9.07 × 10(-3), n= 135). Our data suggest a genetic and functional association of MPP7 with BMD variation.

  3. Feasibility study on utilization of associated gas as CNG

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-03-01

    The Back Ho oilfield is the largest oilfield in Vietnam and at the same time is producing the largest amount of natural gas (associated gas) in Vietnam. Although the majority of the associated gas has been used in the power generation plant, a large amount of surplus gas is not effectively used because of shortage of fund and technologies. Accordingly, a feasibility study has been executed for a project to compress 20% of the associated gas into CNG, and use it effectively as automobile and factory fuel. As a result of the site survey, it was found that, although Vietnam consumes less amount of energy and emits less amount of CO2, the nation has a strong interest and a large amount of knowledge about global warming and CDM because the country is subjected to large effect of warming. Furthermore, it has been reconfirmed that introducing CNG into this territory is highly effective. Discussions have been made on places of installing the facilities, effective surplus gas utilization systems, facility specifications, utilities, and number of workers. Calculations were made on approximate cost of the facilities and the running cost. As a result of the surveys and discussions, it was determined that technological support from Japan and the Yen loan for environment with low interest rate are necessary. (NEDO)

  4. Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study

    Directory of Open Access Journals (Sweden)

    Paccaud Fred

    2011-09-01

    Full Text Available Abstract Background Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR and albuminuria independently of each other. We also investigated the association of MTHFR polymorphisms related to homocysteine with albuminuria to get further insight into causality. Methods This was a cross-sectional population-based study in Caucasians (n = 5913. Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g. Results Uric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, P P for trend P P = 0.004 were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. MTHFR alleles related to higher homocysteine were associated with increased risk of albuminuria. Conclusions In the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.

  5. The association between obesity and back pain in nine countries: a cross-sectional study.

    Science.gov (United States)

    Koyanagi, Ai; Stickley, Andrew; Garin, Noe; Miret, Marta; Ayuso-Mateos, Jose Luis; Leonardi, Matilde; Koskinen, Seppo; Galas, Aleksander; Haro, Josep Maria

    2015-02-11

    The association between obesity and back pain has mainly been studied in high-income settings with inconclusive results, and data from older populations and developing countries are scarce. The aim of this study was to assess this association in nine countries in Asia, Africa, Europe, and Latin America among older adults using nationally-representative data. Data on 42116 individuals ≥50 years who participated in the Collaborative Research on Ageing in Europe (COURAGE) study conducted in Finland, Poland, and Spain in 2011-2012, and the World Health Organization's Study on Global Ageing and Adult Health (SAGE) conducted in China, Ghana, India, Mexico, Russia, and South Africa in 2007-2010 were analysed. Information on measured height and weight available in the two datasets was used to calculate Body Mass Index (BMI). Self-reported back pain occurring in the past 30 days was the outcome. Multivariable logistic regression analysis was used to assess the association between BMI and back pain. The prevalence of back pain ranged from 21.5% (China) to 57.5% (Poland). In the multivariable analysis, compared to BMI 18.5-24.9 kg/m(2), significantly higher odds for back pain were observed for BMI ≥35 kg/m(2) in Finland (OR 3.33), Russia (OR 2.20), Poland (OR 2.03), Spain (OR 1.56), and South Africa (OR 1.48); BMI 30.0-34.0 kg/m(2) in Russia (OR 2.76), South Africa (OR 1.51), and Poland (OR 1.47); and BMI 25.0-29.9 kg/m(2) in Russia (OR 1.51) and Poland (OR 1.40). No significant associations were found in the other countries. The strength of the association between obesity and back pain may vary by country. Future studies are needed to determine the factors contributing to differences in the associations observed.

  6. Trajectories of neighborhood poverty and associations with subclinical atherosclerosis and associated risk factors: the multi-ethnic study of atherosclerosis.

    Science.gov (United States)

    Murray, Emily T; Diez Roux, Ana V; Carnethon, Mercedes; Lutsey, Pamela L; Ni, Hanyu; O'Meara, Ellen S

    2010-05-15

    The authors used data from the Multi-Ethnic Study of Atherosclerosis and latent trajectory class modeling to determine patterns of neighborhood poverty over 20 years (1980-2000 residential history questionnaires were geocoded and linked to US Census data). Using these patterns, the authors examined 1) whether trajectories of neighborhood poverty were associated with differences in the amount of subclinical atherosclerosis (common carotid intimal-media thickness) and 2) associated risk factors (body mass index, hypertension, diabetes, current smoking) at baseline (January 2000-August 2002). The authors found evidence of 5 stable trajectory groups with differing levels of neighborhood poverty ( approximately 6%, 12%, 20%, 30%, and 45%) and 1 group with 29% poverty in 1980 and approximately 11% in 2000. Mostly for women, higher cumulative neighborhood poverty was generally significantly associated with worse cardiovascular outcomes. Trends generally persisted after adjustment for adulthood socioeconomic position and race/ethnicity, although they were no longer statistically significant. Among women who had moved during the 20 years, the long-term measure had stronger associations with outcomes (except smoking) than a single, contemporaneous measure. Results indicate that cumulative 20-year exposure to neighborhood poverty is associated with greater cardiovascular risk for women. In residentially mobile populations, single-point-in-time measures underestimate long-term effects.

  7. Autism and genetics: Clinical approach and association study with two markers of HRAS gene

    Energy Technology Data Exchange (ETDEWEB)

    Herault, J.; Petit, E.; Cherpi, C. [Laboratoire de Biochimie Medicale, Tours (France)] [and others

    1995-08-14

    Twin studies and familial aggregation studies indicate that genetic factors could play a role in infantile autism. In an earlier study, we identified a possible positive association between autism and a c-Harvey-ras (HRAS) oncogene marker at the 3{prime} end of the coding region. In an attempt to confirm this finding, we studied a larger population, well-characterized clinically and genetically. We report a positive association between autism and two HRAS markers, the 3{prime} marker used in the initial study and an additional marker in exon 1. 46 refs., 1 fig., 2 tabs.

  8. 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.

  9. A Genome-wide Association Study of Myasthenia Gravis

    Science.gov (United States)

    Renton, Alan E.; Pliner, Hannah A.; Provenzano, Carlo; Evoli, Amelia; Ricciardi, Roberta; Nalls, Michael A.; Marangi, Giuseppe; Abramzon, Yevgeniya; Arepalli, Sampath; Chong, Sean; Hernandez, Dena G.; Johnson, Janel O.; Bartoccioni, Emanuela; Scuderi, Flavia; Maestri, Michelangelo; Raphael Gibbs, J.; Errichiello, Edoardo; Chiò, Adriano; Restagno, Gabriella; Sabatelli, Mario; Macek, Mark; Scholz, Sonja W.; Corse, Andrea; Chaudhry, Vinay; Benatar, Michael; Barohn, Richard J.; McVey, April; Pasnoor, Mamatha; Dimachkie, Mazen M.; Rowin, Julie; Kissel, John; Freimer, Miriam; Kaminski, Henry J.; Sanders, Donald B.; Lipscomb, Bernadette; Massey, Janice M.; Chopra, Manisha; Howard, James F.; Koopman, Wilma J.; Nicolle, Michael W.; Pascuzzi, Robert M.; Pestronk, Alan; Wulf, Charlie; Florence, Julaine; Blackmore, Derrick; Soloway, Aimee; Siddiqi, Zaeem; Muppidi, Srikanth; Wolfe, Gil; Richman, David; Mezei, Michelle M.; Jiwa, Theresa; Oger, Joel; Drachman, Daniel B.; Traynor, Bryan J.

    2016-01-01

    IMPORTANCE Myasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood. OBJECTIVE To identify genetic variants that alter susceptibility to myasthenia gravis, we performed a genome-wide association study. DESIGN, SETTING, AND PARTICIPANTS DNA was obtained from 1032 white individuals from North America diagnosed as having acetylcholine receptor antibody–positive myasthenia gravis and 1998 race/ethnicity-matched control individuals from January 2010 to January 2011. These samples were genotyped on Illumina OmniExpress single-nucleotide polymorphism arrays. An independent cohort of 423 Italian cases and 467 Italian control individuals were used for replication. MAIN OUTCOMES AND MEASURES We calculated P values for association between 8114394 genotyped and imputed variants across the genome and risk for developing myasthenia gravis using logistic regression modeling. A threshold P value of 5.0 × 10−8 was set for genome-wide significance after Bonferroni correction for multiple testing. RESULTS In the over all case-control cohort, we identified association signals at CTLA4 (rs231770; P = 3.98 × 10−8; odds ratio, 1.37; 95% CI, 1.25–1.49), HLA-DQA1 (rs9271871; P = 1.08 × 10−8; odds ratio, 2.31; 95% CI, 2.02 – 2.60), and TNFRSF11A (rs4263037; P = 1.60 × 10−9; odds ratio, 1.41; 95% CI, 1.29–1.53). These findings replicated for CTLA4 and HLA-DQA1 in an independent cohort of Italian cases and control individuals. Further analysis revealed distinct, but overlapping, disease-associated loci for early- and late-onset forms of myasthenia gravis. In the late-onset cases, we identified 2 association peaks: one was located in TNFRSF11A (rs4263037; P = 1.32 × 10−12; odds ratio, 1.56; 95% CI, 1.44–1.68) and the other was detected

  10. Associations between male infertility and ancestry in South Americans: a case control study.

    Science.gov (United States)

    Skowronek, Maria Fernanda; Velazquez, Tatiana; Mut, Patricia; Figueiro, Gonzalo; Sans, Monica; Bertoni, Bernardo; Sapiro, Rossana

    2017-07-26

    Infertility affects 15% of human couples, with men being responsible in approximately 50% of cases. Moreover, the aetiology of male factor infertility is poorly understood. The majority of male factor infertility remains idiopathic and potentially genetic in origin. The association of the Y chromosome and mitochondrial haplogroups with male infertility has been previously reported. This association differs between studied populations and their geographical distributions. These effects have been only rarely analysed in mixed populations, such as South Americans. In this study, we analysed the contributions of the Y chromosome and mitochondrial haplogroups to male infertility in a mixed population. A case control study was conducted. Regular PCR and high-resolutionmelting- real-time PCR were performed to type haplogroups from fertile and infertile men. The sperm parameters from infertile men were compared in each haplogroup by logistic regression analysis and ANOVA. The genotyping confirmed the known admixture characteristic of the Uruguayan population. The European paternal contribution was higher than the maternal contribution in both fertile and infertile men. Neither maternal nor paternal ancestry presented differences between the cases and controls. Men belonging to the Y chromosome haplogroup F(xK) more frequently presented with an abnormal sperm morphology than men from other haplogroups. The sperm parameters were not associated with the mitochondrial haplogroups. The data presented in this study showed an association between male infertility and ancestry in the Uruguayan population. Specifically, abnormal sperm morphology was associated with the Y chromosome haplogroup F(xK). Since the Y chromosome lacks recombination, these data suggest that some genes that determine sperm morphology might be inherited in blocks with the region that determines specific haplogroups. However, the possible association between the Y chromosome haplogroup F(xK) and sperm

  11. Integration of least angle regression with empirical Bayes for multi-locus genome-wide association studies

    Science.gov (United States)

    Multi-locus genome-wide association studies has become the state-of-the-art procedure to identify quantitative trait loci (QTL) associated with traits simultaneously. However, implementation of multi-locus model is still difficult. In this study, we integrated least angle regression with empirical B...

  12. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    L.V. Wain (Louise); G.C. Verwoert (Germaine); P.F. O'Reilly (Paul); G. Shi (Gang); T. Johnson (Toby); M. Bochud (Murielle); K. Rice (Kenneth); P. Henneman (Peter); A.V. Smith (Albert Vernon); G.B. Ehret (Georg); N. Amin (Najaf); M.G. Larson (Martin); V. Mooser (Vincent); D. Hadley (David); M. Dörr (Marcus); J.C. Bis (Joshua); T. Aspelund (Thor); T. Esko (Tõnu); A.C.J.W. Janssens (Cécile); J.H. Zhao (Jing Hua); S.C. Heath (Simon); M. Laan (Maris); J. Fu (Jingyuan); G. Pistis (Giorgio); J. Luan; G. Lucas (Gavin); N. Pirastu (Nicola); I. Pichler (Irene); A.U. Jackson (Anne); R.J. Webster (Rebecca J.); F.F. Zhang; J. Peden (John); R. Schmidt (Reinhold); T. Tanaka (Toshiko); H. Campbell (Harry); W. Igl (Wilmar); Y. Milaneschi (Yuri); J.J. Hottenga (Jouke Jan); V. Vitart (Veronique); D.I. Chasman (Daniel); S. Trompet (Stella); J.L. Bragg-Gresham (Jennifer L.); B.Z. Alizadeh (Behrooz); J.C. Chambers (John); X. Guo (Xiuqing); T. Lehtimäki (Terho); B. Kuhnel (Brigitte); L.M. Lopez; O. Polasek (Ozren); M. Boban (Mladen); C.P. Nelson (Christopher P.); A.C. Morrison (Alanna); V. Pihur (Vasyl); S.K. Ganesh (Santhi); A. Hofman (Albert); S. Kundu (Suman); F.U.S. Mattace Raso (Francesco); F. Rivadeneira Ramirez (Fernando); E.J.G. Sijbrands (Eric); A.G. Uitterlinden (André); S.J. Hwang; R.S. Vasan (Ramachandran Srini); Y.A. Wang (Ying); S.M. Bergmann (Sven); P. Vollenweider (Peter); G. Waeber (Gérard); J. Laitinen (Jaana); A. Pouta (Anneli); P. Zitting (Paavo); W.L. McArdle (Wendy); H.K. Kroemer (Heyo); U. Völker (Uwe); H. Völzke (Henry); N.L. Glazer (Nicole); K.D. Taylor (Kent); T.B. Harris (Tamara); H. Alavere (Helene); T. Haller (Toomas); A. Keis (Aime); M.L. Tammesoo; Y.S. Aulchenko (Yurii); K-T. Khaw (Kay-Tee); P. Galan (Pilar); S. Hercberg (Serge); G.M. Lathrop (Mark); S. Eyheramendy (Susana); E. Org (Elin); S. Sõber (Siim); X. Lu (Xiaowen); I.M. Nolte (Ilja); B.W.J.H. Penninx (Brenda); T. Corre (Tanguy); C. Masciullo (Corrado); C. Sala (Cinzia); L. Groop (Leif); B.F. Voight (Benjamin); O. Melander (Olle); C.J. O'Donnell (Christopher); V. Salomaa (Veikko); P. d' Adamo (Pio); A. Fabretto (Antonella); F. Faletra (Flavio); S. Ulivi (Shelia); F. Del Greco M (Fabiola); M.F. Facheris (Maurizio); F.S. Collins (Francis); R.N. Bergman (Richard); J.P. Beilby (John); J. Hung (Judy); A.W. Musk (Arthur); M. Mangino (Massimo); S.Y. Shin (So Youn); N. Soranzo (Nicole); H. Watkins (Hugh); A. Goel (Anuj); A. Hamsten (Anders); P. Gider (Pierre); M. Loitfelder (Marisa); M. Zeginigg (Marion); D.G. Hernandez (Dena); S.S. Najjar (Samer); P. Navarro (Pau); S.H. Wild (Sarah); A.M. Corsi (Anna Maria); A. Singleton (Andrew); E.J.C. de Geus (Eco); G.A.H.M. Willemsen (Gonneke); A.N. Parker (Alex); L.M. Rose (Lynda); B.M. Buckley (Brendan M.); D.J. Stott (David. J.); M. Orrù (Marco); M. Uda (Manuela); M.M. van der Klauw (Melanie); X. Li (Xiaohui); J. Scott (James); Y.D.I. Chen (Yii-Der Ida); G.L. Burke (Greg); M. Kähönen (Mika); J. Viikari (Jorma); A. Döring (Angela); T. Meitinger (Thomas); G.S. Davis; J.M. Starr (John); V. Emilsson (Valur); A.S. Plump (Andrew); J.H. Lindeman (Jan H.); P.A.C. 't Hoen (Peter); I.R. König (Inke); J.F. Felix (Janine); R. Clarke; J. Hopewell; H. Ongen (Halit); M.M.B. Breteler (Monique); S. Debette (Stéphanie); A.L. DeStefano (Anita); M. Fornage (Myriam); G.F. Mitchell (Gary); H. Holm (Hilma); K. Stefansson (Kari); G. Thorleifsson (Gudmar); U. Thorsteinsdottir (Unnur); N.J. Samani (Nilesh); M. Preuss (Michael); I. Rudan (Igor); C. Hayward (Caroline); I.J. Deary (Ian); H.E. Wichmann (Heinz Erich); O. Raitakari (Olli); W. Palmas (Walter); J.S. Kooner (Jaspal); R.P. Stolk (Ronald); J.W. Jukema (Jan Wouter); A.F. Wright (Alan); D.I. Boomsma (Dorret); S. Bandinelli (Stefania); U. Gyllensten (Ulf); J.F. Wilson (James); L. Ferrucci (Luigi); M. Farrall (Martin); T.D. Spector (Timothy); L.J. Palmer; J. Tuomilehto (Jaakko); A. Pfeufer (Arne); P. Gasparini (Paolo); D.S. Siscovick (David); D. Altshuler (David); R.J.F. Loos (Ruth); D. Toniolo (Daniela); H. Snieder (Harold); C. Gieger (Christian); P. Meneton (Pierre); N.J. Wareham (Nick); B.A. Oostra (Ben); A. Metspalu (Andres); L.J. Launer (Lenore); R. Rettig (Rainer); D.P. Strachan (David); J.S. Beckmann (Jacques); J.C.M. Witteman (Jacqueline); J.A.P. Willems van Dijk (Ko); E.A. Boerwinkle (Eric); M. Boehnke (Michael); P.M. Ridker (Paul); M.R. Järvelin; A. Chakravarti (Aravinda); J. Erdmann (Jeanette); V. Gudnason (Vilmundur); C. Newton-Cheh (Christopher); D. Levy (Daniel); P. Arora (Pankaj); P. Munroe (Patricia); B.M. Psaty (Bruce); M. Caulfield (Mark); D.C. Rao (Dabeeru C.); P. Elliott (Paul); P. Tikka-Kleemola (Päivi); G.R. Abecasis (Gonçalo); I.E. Barroso (Inês)

    2011-01-01

    textabstractNumerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N =

  13. Epigenome-Wide Association Study of Tic Disorders.

    Science.gov (United States)

    Zilhão, Nuno R; Padmanabhuni, Shanmukha S; Pagliaroli, Luca; Barta, Csaba; Smit, Dirk J A; Cath, Danielle; Nivard, Michel G; Baselmans, Bart M L; van Dongen, Jenny; Paschou, Peristera; Boomsma, Dorret I

    2015-12-01

    Tic disorders are moderately heritable common psychiatric disorders that can be highly troubling, both in childhood and in adulthood. In this study, we report results obtained in the first epigenome-wide association study (EWAS) of tic disorders. The subjects are participants in surveys at the Netherlands Twin Register (NTR) and the NTR biobank project. Tic disorders were measured with a self-report version of the Yale Global Tic Severity Scale Abbreviated version (YGTSS-ABBR), included in the 8th wave NTR data collection (2008). DNA methylation data consisted of 411,169 autosomal methylation sites assessed by the Illumina Infinium HumanMethylation450 BeadChip Kit (HM450k array). Phenotype and DNA methylation data were available in 1,678 subjects (mean age = 41.5). No probes reached genome-wide significance (p tic disorders. The top significantly enriched gene ontology (GO) terms among higher ranking methylation sites included anatomical structure morphogenesis (GO:0009653, p = 4.6 × 10-(15)) developmental process (GO:0032502, p = 2.96 × 10(-12)), and cellular developmental process (GO:0048869, p = 1.96 × 10(-12)). Overall, these results provide a first insight into the epigenetic mechanisms of tic disorders. This first study assesses the role of DNA methylation in tic disorders, and it lays the foundations for future work aiming to unravel the biological mechanisms underlying the architecture of this disorder.

  14. The multistep road to ventilator-associated lung abscess: A retrospective study of S.aureus ventilator-associated pneumonia.

    Science.gov (United States)

    Mounier, Roman; Lobo, David; Voulgaropoulos, Julia; Martin, Mathieu; Aït-Mamar, Bouziane; Bitot, Valérie; Jost, Paul-Henri; Birnbaum, Ron; Nebbad, Biba; Cook, Fabrice; Dhonneur, Gilles

    2017-01-01

    We observed some cases of lung abscess (LA) in ICU patients suffering S.aureus ventilator-associated pneumonia (S.aureus-VAP). We aimed to assess which of the host and/or bacteria-related features are associated with LA. We conducted a retrospective study from January 2009 to July 2013 in a trauma surgical ICU within a teaching hospital. All adult patients presenting with S.aureus-VAP were included. We compared two groups of patients according to the formation or not of LA concomitantly to S.aureus-VAP. Seventy-nine S.aureus-VAP patients, predominantly males (85%) of rather young age (mean [SD]: 35yr [21-64]) with severe trauma (initial Simplified Acute Score II = 42 [32-52]) related-ICU admission, were included. Among them, 10 (14%) developed LA. Patient's characteristics significantly associated with LA development were: a younger age (p = 0.003), road traffic accidents admission (p = 0.017), head injury (p = 0.002), lower Glasgow Coma Scale (p = 0.009), blunt chest trauma (p = 0.01) pneumothorax (p = 0.01) and lung contusions (p = 0.002). No microbiological factors were significantly associated with LA formation. Abscesses were mostly bilateral, ≥5 cm of diameter and with a posterior location. Our results do not favor a specific virulence of S.aureus, but rather highlight the role of multiple insults to the lung, promoting LA formation. Despite a similar severity score, patients with LA had more serious trauma, combining severe both chest and head insults.

  15. 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

  16. Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population.

    Directory of Open Access Journals (Sweden)

    Po-Hsiu Kuo

    Full Text Available Autism spectrum disorder (ASD is a neurodevelopmental disorder with strong genetic components. Several recent genome-wide association (GWA studies in Caucasian samples have reported a number of gene regions and loci correlated with the risk of ASD--albeit with very little consensus across studies.A two-stage GWA study was employed to identify common genetic variants for ASD in the Taiwanese Han population. The discovery stage included 315 patients with ASD and 1,115 healthy controls, using the Affymetrix SNP array 6.0 platform for genotyping. Several gene regions were then selected for fine-mapping and top markers were examined in extended samples. Single marker, haplotype, gene-based, and pathway analyses were conducted for associations.Seven SNPs had p-values ranging from 3.4~9.9*10-6, but none reached the genome-wide significant level. Five of them were mapped to three known genes (OR2M4, STYK1, and MNT with significant empirical gene-based p-values in OR2M4 (p = 3.4*10(-5 and MNT (p = 0.0008. Results of the fine-mapping study showed single-marker associations in the GLIS1 (rs12082358 and rs12080993 and NAALADL2 (rs3914502 and rs2222447 genes, and gene-based associations for the OR2M3-OR2T5 (olfactory receptor genes, p = 0.02, and GLIPR1/KRR1 gene regions (p = 0.015. Pathway analyses revealed important pathways for ASD, such as olfactory and G protein-coupled receptors signaling pathways.We reported Taiwanese Han specific susceptibility genes and variants for ASD. However, further replication in other Asian populations is warranted to validate our findings. Investigation in the biological functions of our reported genetic variants might also allow for better understanding on the underlying pathogenesis of autism.

  17. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.

    2008-01-01

    allele OR, 0.95; 95% CI, 0.91-0.99; P(trend) = 0.028). This association was somewhat stronger for estrogen receptor-positive tumors (OR, 0.92; 95% CI, 0.87-0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer......Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...

  18. 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.

  19. Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.

    Directory of Open Access Journals (Sweden)

    Hsin-Chou Yang

    Full Text Available Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP quality, four SNPs from two SNP triplets with strong association signals (-log(10(p>7 and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (-log(10(p>8 were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population.

  20. Periodontitis is associated with endothelial dysfunction in a general population: a cross-sectional study.

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    Birte Holtfreter

    Full Text Available A large body of evidence underlines an association between periodontal disease and cardiovascular disease. In contrast, data on its relation with endothelial dysfunction as a marker of early subclinical atherosclerosis is inconclusive and limited to patient-cohort studies. We therefore investigated the association between periodontal disease and flow-mediated dilation of the brachial artery (FMD as a measure of endothelial dysfunction in a general population, and also addressed a possible mediation via inflammation. The study population comprised 1,234 subjects (50.5% men aged 25-85 years from the 5-year follow-up of the Study of Health in Pomerania, a population-based cohort study. Clinical attachment loss (CAL and pocket probing depth (PPD as measures of periodontal disease were assessed half-mouth at four sites per tooth. Subjects were classified according to the periodontitis case definition proposed by Tonetti and Claffey (2005. Measurements of FMD and nitroglycerin-mediated dilation (NMD were performed using standardized ultrasound techniques. High-sensitive C-reactive protein, fibrinogen and leukocyte count were measured. Fully adjusted multivariate linear regression analyses revealed significant associations of the percentage of sites with PPD ≥ 6 mm with FMD (p(trend=0.048, with subjects within the highest category having a 0.74% higher FMD compared to subjects within the lowest category (p<0.05. Consistently, FMD values increased significantly across categories of the percentage of sites with CAL ≥ 6 mm (p(trend=0.01 and the periodontitis case definition (p(trend=0.006. Restrictions to subjects without antihypertensive or statin medication or current non-smokers confirmed previous results. Systemic inflammation did not seem to mediate the relation. Both PPD and CAL were not consistently associated with NMD. In contrast to previous studies, high levels of periodontal disease were significantly associated with high FMD values. This

  1. Disease-Concordant Twins Empower Genetic Association Studies

    DEFF Research Database (Denmark)

    Tan, Qihua; Li, Weilong; Vandin, Fabio

    2017-01-01

    and ordinary healthy samples as controls. We examined the power gain of the twin-based design for various scenarios (i.e., cases from monozygotic and dizygotic twin pairs concordant for a disease) and compared the power with the ordinary case-control design with cases collected from the unrelated patient...... concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease-concordant twin design, which uses singletons from disease-concordant twin pairs as cases...... population. Simulation was done by assigning various allele frequencies and allelic relative risks for different mode of genetic inheritance. In general, for achieving a power estimate of 80%, the sample sizes needed for dizygotic and monozygotic twin cases were one half and one fourth of the sample size...

  2. 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...

  3. 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.

  4. Association of cardiovascular risk factors between Hispanic/Latino parents and youth: the Hispanic Community Health Study/Study of Latino Youth.

    Science.gov (United States)

    Carnethon, Mercedes R; Ayala, Guadalupe X; Bangdiwala, Shrikant I; Bishop, Virginia; Daviglus, Martha L; Delamater, Alan M; Gallo, Linda C; Perreira, Krista; Pulgaron, Elizabeth; Reina, Samantha; Talavera, Gregory A; Van Horn, Linda H; Isasi, Carmen R

    2017-04-01

    Hispanic/Latinos have a high burden of cardiovascular disease (CVD) risk factors which may begin at young ages. We tested the association of CVD risk factors between Hispanic/Latino parents and their children. We conducted a cross-sectional study in the Hispanic Community Health Study/Study of Latinos Youth study. Girls (n = 674) and boys (n = 667) aged 8 to 16 years (mean age 12.1 years) and their parents (n = 942) had their CVD risk factors measured. CVD risk factors in parents were significantly positively associated with those same risk factors among youth. After adjustment for demographic characteristics, diet and physical activity, obese parents were significantly more likely to have youth who were overweight (odds ratios [ORs], 2.39; 95% confidence interval [CI], 1.20-4.76) or obese (OR, 6.16; 95% CI, 3.23-11.77) versus normal weight. Dyslipidemia among parents was associated with 1.98 higher odds of dyslipidemia among youth (95% CI, 1.37-2.87). Neither hypertension nor diabetes was associated with higher odds of high blood pressure or hyperglycemia (prediabetes or diabetes) in youth. Findings were consistent by sex and in younger (age parents, which portends high risk for adult CVD. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Endothelial dysfunction is associated with carotid plaque: a cross-sectional study from the population based Northern Manhattan Study

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    Boden-Albala Bernadette

    2006-08-01

    Full Text Available Abstract Background Impaired vascular function occurs early in atherogenesis. Brachial flow mediated dilatation (FMD is a non-invasive measure of vascular function and may be an important marker of preclinical atherosclerosis. Data on the association between FMD and carotid plaque in multi-ethnic populations are limited. The objective of this study was to determine whether endothelial dysfunction is independently associated with carotid plaque in a community of northern Manhattan. Methods In the population-based Northern Manhattan Study (NOMAS, high-resolution B-mode ultrasound images of the brachial and carotid arteries were obtained in 643 stroke-free subjects (mean age 66 years; 55% women; 65% Caribbean-Hispanic, 17% African-American, 16% Caucasian. Brachial FMD was measured during reactive hyperemia. Maximum carotid plaque thickness (MCPT was measured at the peak plaque prominence. Results The mean brachial FMD was 5.78 ± 3.83 %. Carotid plaque was present in 339 (53% subjects. The mean MCPT was 1.68 ± 0.82 mm, and the 75th percentile was 2.0 mm. Reduced FMD was significantly associated with increased MCPT. After adjusting for demographics, vascular risk factors, and education, each percent of FMD decrease was associated with a significant 0.02 mm increase in MCPT (p = 0.028. In a dichotomous adjusted model, blunted FMD was associated with an increased risk of MCPT ≥ 2.0 mm (OR, 1.11 for every 1% decrease in FMD; 95% CI, 1.03–1.19. Conclusion Decreased brachial FMD is independently associated with carotid plaque. Non-invasive evaluation of endothelial dysfunction may be a useful marker of preclinical atherosclerosis and help to individualize cardiovascular risk assessment beyond traditional risk factors.

  6. Genome-wide association study of Stayability and Heifer Pregnancy in Red Angus cattle.

    Science.gov (United States)

    Speidel, S E; Buckley, B A; Boldt, R J; Enns, R M; Lee, J; Spangler, M L; Thomas, M G

    2018-04-03

    Reproductive performance is the most important component of cattle production from the standpoint of economic sustainability of commercial beef enterprises. Heifer Pregnancy (HPG) and Stayability (STAY) genetic predictions are 2 selection tools published by the Red Angus Association of America (RAAA) to assist with improvements in reproductive performance. Given the importance of HPG and STAY to the profitability of commercial beef enterprises, the objective of this study was to identify QTL associated with both HPG and STAY in Red Angus cattle. A genome-wide association study (GWAS) was performed using deregressed HPG and STAY EBV, calculated using a single-trait animal model and a 3-generation pedigree with data from the Spring 2015 RAAA National Cattle Evaluation. Each individual animal possessed 74,659 SNP genotypes. Individual animals with a deregressed EBV reliability > 0.05 were merged with the genotype file and marker quality control was performed. Criteria for sifting genotypes consisted of removing those markers where any of the following were found: average call rate less than 0.85, minor allele frequency 0.99). These criteria resulted in 2,664 animals with 62,807 SNP available for GWAS. Association studies were performed using a Bayes Cπ model in the BOLT software package. Marker significance was calculated as the posterior probability of inclusion (PPI), or the number of instances a specific marker was sampled divided by the total number of samples retained from the Markov chain Monte Carlo chains. Nine markers, with a PPI ≥ 3% were identified as QTL associated with HPG on BTA 1, 11, 13, 23, and 29. Twelve markers, with a PPI ≥ 75% were identified as QTL associated with STAY on BTA 6, 8, 9, 12, 15, 18, 22, and 23.

  7. Association between osteoporosis and urinary calculus: evidence from a population-based study.

    Science.gov (United States)

    Keller, J J; Lin, C-C; Kang, J-H; Lin, H-C

    2013-02-01

    This population-based case-control analysis investigated the association between osteoporosis and prior urinary calculus (UC) in Taiwan. We succeeded in detecting an association between osteoporosis and prior UC (adjusted odds ratio = 1.66). This association was consistent and significant regardless of stone location. UC has been demonstrated to be a risk factor for osteoporotic fractures, but no studies to date have directly investigated the association between UC and osteoporosis. This case-control analysis aimed to investigate the association of osteoporosis with prior UC using a population-based dataset in Taiwan. We first identified 39,840 cases ≥40 years who received their first-time diagnosis of osteoporosis between 2002 and 2009 and then randomly selected 79,680 controls. We used conditional logistic regression analyses to compute the odds ratio (OR) and the corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. The OR of having been previously diagnosed with UC for patients with osteoporosis was 1.66 (95 % CI = 1.59-1.73) when compared to controls after adjusting for geographic location, urbanization level, type I diabetes mellitus, coronary heart disease, hyperlipidemia, rheumatoid arthritis, stroke, renal disease, Parkinson's disease, hyperthyroidism, chronic hepatopathy, Cushing's syndrome, malabsorption, gastrectomy, obesity, and alcohol abuse/alcohol dependence syndrome. The results consistently showed that osteoporosis was significantly associated with a previous diagnosis of UC regardless of stone location; the adjusted ORs of prior kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.71 (95 % CI = 1.61-1.81), 1.60 (95 % CI = 1.47-1.74), 1.59 (95 % CI = 1.23-2.04), and 1.69 (95 % CI = 1.59-1.80), respectively. This study succeeded in detecting an association between osteoporosis and prior UC. In addition

  8. 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 

  9. Association Between Geographic Elevation, Bone Status, and Exercise Habits: The Shimane CoHRE Study.

    Science.gov (United States)

    Takeda, Miwako; Hamano, Tsuyoshi; Kohno, Kunie; Yano, Shozo; Shiwaku, Kuninori; Nabika, Toru

    2015-06-30

    In recent years, there has been growing interest in the association between the residential environment and health. The association between residential environment (i.e., geographic elevation) and bone status is unknown. Furthermore, these associations could differ by exercise habits due to the chronically greater daily activity caused by steep slopes in mountainous areas. The aim of this study was to test whether the association between bone status of elderly people measured using quantitative ultrasound (QUS) and elevation varied according to the exercise habits in a mountainous area population. Data were collected from a cross-sectional study conducted during 2012-2013. QUS value was expressed as a proportion of the young adult mean (%YAM), with higher scores donating better bone status. After excluding subjects with missing data, we analyzed the data for 321 men and 500 women. Our results indicate that %YAM was not associated with elevation among men, or among women with exercise habits. However, elevation was associated with %YAM among women without exercise habits. Our results highlight the importance of considering residential environment and exercise habits when establishing promotion strategies to maintain bone status of the elderly people who live in rural mountainous areas.

  10. Association Between Geographic Elevation, Bone Status, and Exercise Habits: The Shimane CoHRE Study

    Directory of Open Access Journals (Sweden)

    Miwako Takeda

    2015-06-01

    Full Text Available In recent years, there has been growing interest in the association between the residential environment and health. The association between residential environment (i.e., geographic elevation and bone status is unknown. Furthermore, these associations could differ by exercise habits due to the chronically greater daily activity caused by steep slopes in mountainous areas. The aim of this study was to test whether the association between bone status of elderly people measured using quantitative ultrasound (QUS and elevation varied according to the exercise habits in a mountainous area population. Data were collected from a cross-sectional study conducted during 2012–2013. QUS value was expressed as a proportion of the young adult mean (%YAM, with higher scores donating better bone status. After excluding subjects with missing data, we analyzed the data for 321 men and 500 women. Our results indicate that %YAM was not associated with elevation among men, or among women with exercise habits. However, elevation was associated with %YAM among women without exercise habits. Our results highlight the importance of considering residential environment and exercise habits when establishing promotion strategies to maintain bone status of the elderly people who live in rural mountainous areas.

  11. Genome-wide association study of Lp-PLA(2 activity and mass in the Framingham Heart Study.

    Directory of Open Access Journals (Sweden)

    Sunil Suchindran

    2010-04-01

    Full Text Available Lipoprotein-associated phospholipase A(2 (Lp-PLA(2 is an emerging risk factor and therapeutic target for cardiovascular disease. The activity and mass of this enzyme are heritable traits, but major genetic determinants have not been explored in a systematic, genome-wide fashion. We carried out a genome-wide association study of Lp-PLA(2 activity and mass in 6,668 Caucasian subjects from the population-based Framingham Heart Study. Clinical data and genotypes from the Affymetrix 550K SNP array were obtained from the open-access Framingham SHARe project. Each polymorphism that passed quality control was tested for associations with Lp-PLA(2 activity and mass using linear mixed models implemented in the R statistical package, accounting for familial correlations, and controlling for age, sex, smoking, lipid-lowering-medication use, and cohort. For Lp-PLA(2 activity, polymorphisms at four independent loci reached genome-wide significance, including the APOE/APOC1 region on chromosome 19 (p = 6 x 10(-24; CELSR2/PSRC1 on chromosome 1 (p = 3 x 10(-15; SCARB1 on chromosome 12 (p = 1x10(-8 and ZNF259/BUD13 in the APOA5/APOA1 gene region on chromosome 11 (p = 4 x 10(-8. All of these remained significant after accounting for associations with LDL cholesterol, HDL cholesterol, or triglycerides. For Lp-PLA(2 mass, 12 SNPs achieved genome-wide significance, all clustering in a region on chromosome 6p12.3 near the PLA2G7 gene. Our analyses demonstrate that genetic polymorphisms may contribute to inter-individual variation in Lp-PLA(2 activity and mass.

  12. Pneumothorax associated with nontuberculous mycobacteria: A retrospective study of 69 patients.

    Science.gov (United States)

    Ueyama, Masako; Asakura, Takanori; Morimoto, Kozo; Namkoong, Ho; Matsuda, Shuichi; Osawa, Takeshi; Ishii, Makoto; Hasegawa, Naoki; Kurashima, Atsuyuki; Goto, Hajime

    2016-07-01

    The incidence of nontuberculous mycobacterial pulmonary disease (NTMPD) is increasing worldwide. Secondary spontaneous pneumothorax occurs as a complication of underlying lung disease and is associated with higher morbidity, mortality, and recurrence than primary spontaneous pneumothorax. We here investigated the clinical features and long-term outcomes of pneumothorax associated with NTMPD.We conducted a retrospective study on consecutive adult patients with pneumothorax associated with NTMPD at Fukujuji Hospital and Keio University Hospital from January 1992 to December 2013. We reviewed the medical records of 69 such patients to obtain clinical characteristics, radiological findings, and long-term outcomes, including pneumothorax recurrence and mortality.The median age of the patients was 68 years; 34 patients were women. The median body mass index was 16.8 kg/m. Underlying pulmonary diseases mainly included chronic obstructive pulmonary disease and pulmonary tuberculosis. On computed tomography, nodules and bronchiectasis were observed in 46 (98%) and 45 (96%) patients, respectively. Consolidation, pleural thickening, interlobular septal thickening, and cavities were most common, and observed in 40 (85%), 40 (85%), 37 (79%), and 36 (77%) patients, respectively. Regarding pneumothorax treatment outcomes, complete and incomplete lung expansion were observed in 49 patients (71%) and 15 patients (22%), respectively. The survival rate after pneumothorax was 48% at 5 years. By the end of the follow-up, 33 patients had died, and the median survival was 4.4 years with a median follow-up period of 1.7 years. The rate of absence of recurrence after the first pneumothorax was 59% at 3 years. By the end of the follow-up, 18 patients had experienced pneumothorax recurrence. Furthermore, 12/18 patients (66%) with recurrent pneumothorax died during the study period. Twenty-three patients (70%) died because of NTMPD progression. Low body mass index (BMI) was a negative

  13. Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry : A genome-wide association study

    NARCIS (Netherlands)

    Allen, Richard J; Porte, Joanne; Braybrooke, Rebecca; Flores, Carlos; Fingerlin, Tasha E; Oldham, Justin M; Guillen-Guio, Beatriz; Ma, Shwu-Fan; Okamoto, Tsukasa; John, Alison E; Obeidat, Ma'en; Yang, Ivana V; Henry, Amanda; Hubbard, Richard B; Navaratnam, Vidya; Saini, Gauri; Thompson, Norma; Booth, Helen L; Hart, Simon P; Hill, Mike R; Hirani, Nik; Maher, Toby M; McAnulty, Robin J; Millar, Ann B; Molyneaux, Philip L; Parfrey, Helen; Rassl, Doris M; Whyte, Moira K B; Fahy, William A; Marshall, Richard P; Oballa, Eunice; Bossé, Yohan; Nickle, David C; Sin, Don D; Timens, Wim; Shrine, Nick; Sayers, Ian; Hall, Ian P; Noth, Imre; Schwartz, David A; Tobin, Martin D; Wain, Louise V; Jenkins, R Gisli

    2017-01-01

    Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high mortality, uncertain cause, and few treatment options. Studies have identified a significant genetic risk associated with the development of IPF; however, mechanisms by which genetic risk factors promote

  14. Assessing the associations of blood metabolites with osteoporosis: a Mendelian randomization study.

    Science.gov (United States)

    Liu, Li; Wen, Yan; Zhang, Lei; Xu, Peng; Liang, Xiao; Du, Yanan; Li, Ping; He, Awen; Fan, QianRui; Hao, Jingcan; Wang, Wenyu; Guo, Xiong; Shen, Hui; Tian, Qing; Zhang, Feng; Deng, Hong-Wen

    2018-03-01

    Osteoporosis is a metabolic bone disease. The impact of blood metabolites on the development of osteoporosis remains elusive now. To explore the relationship between blood metabolites and osteoporosis. We used 2,286 unrelated Caucasian subjects as discovery samples and 3,143 unrelated Caucasian subjects from the Framingham heart study (FHS) as replication samples. Bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry. Genome-wide SNP genotyping was performed using Affymetrix Human SNP Array 6.0 (for discovery samples) and Affymetrix SNP 500K and 50K array (for FHS replication samples). The SNP sets significantly associated with blood metabolites were obtained from a published whole-genome sequencing study. For each subject, the genetic risk score (GRS) of metabolite was calculated from the genotype data of metabolite associated SNP sets. Pearson correlation analysis was conducted to evaluate the potential impact of blood metabolites on the variations bone phenotypes. 10,000 permutations were conducted to calculate the empirical P value and false discovery rate (FDR). 481 blood metabolites were analyzed in this study. We identified multiple blood metabolites associated with hip BMD, such as 1,5-anhydroglucitol(1,5-AG) (Pdiscovery metabolites on the variations of BMD, and identified several candidate blood metabolites for osteoporosis.

  15. The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

    Directory of Open Access Journals (Sweden)

    Poulton Joanna

    2009-04-01

    Full Text Available Abstract Background The mitochondrial DNA (mtDNA T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV. Methods A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer. Results The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93, gender (males 60% vs 53%, P = 0.54, and stage of HIV disease (mean CD4 T cell count 260.7/μL vs. 176/μL, P = 0.21. The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30 in the HIV-associated cardiomyopathy cases and 13.5% (5/37 in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11. Conclusion The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.

  16. Genome-wide association study for ovarian cancer susceptibility using pooled DNA.

    NARCIS (Netherlands)

    Lu, Y.; Chen, X.; Beesley, J.; Johnatty, S.E.; Defazio, A.; Lambrechts, S.; Lambrechts, D.; Despierre, E.; Vergotes, I.; Chang-Claude, J.; Hein, R.; Nickels, S.; Wang-Gohrke, S.; Dork, T.; Durst, M.; Antonenkova, N.; Bogdanova, N.; Goodman, M.T.; Lurie, G.; Wilkens, L.R.; Carney, M.E.; Butzow, R.; Nevanlinna, H.; Heikkinen, T.; Leminen, A.; Kiemeney, L.A.L.M.; Massuger, L.F.A.G.; Altena, A.M. van; Aben, K.K.H.; Kjaer, S.K.; Hogdall, E.; Jensen, A.; Brooks-Wilson, A.; Le, N.; Cook, L.; Earp, M.; Kelemen, L.; Easton, D.; Pharoah, P.; Song, H.; Tyrer, J.; Ramus, S.; Menon, U.; Gentry-Maharaj, A.; Gayther, S.A.; Bandera, E.V.; Olson, S.H.; Orlow, I.; Rodriguez-Rodriguez, L.; MacGregor, S.; Chenevix-Trench, G.

    2012-01-01

    Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in

  17. Unraveling the genetic etiology of adult antisocial behavior: a genome-wide association study.

    Directory of Open Access Journals (Sweden)

    Jorim J Tielbeek

    Full Text Available Crime poses a major burden for society. The heterogeneous nature of criminal behavior makes it difficult to unravel its causes. Relatively little research has been conducted on the genetic influences of criminal behavior. The few twin and adoption studies that have been undertaken suggest that about half of the variance in antisocial behavior can be explained by genetic factors. In order to identify the specific common genetic variants underlying this behavior, we conduct the first genome-wide association study (GWAS on adult antisocial behavior. Our sample comprised a community sample of 4816 individuals who had completed a self-report questionnaire. No genetic polymorphisms reached genome-wide significance for association with adult antisocial behavior. In addition, none of the traditional candidate genes can be confirmed in our study. While not genome-wide significant, the gene with the strongest association (p-value = 8.7×10(-5 was DYRK1A, a gene previously related to abnormal brain development and mental retardation. Future studies should use larger, more homogeneous samples to disentangle the etiology of antisocial behavior. Biosocial criminological research allows a more empirically grounded understanding of criminal behavior, which could ultimately inform and improve current treatment strategies.

  18. Association between variations in the fat mass and obesity-associated gene and pancreatic cancer risk: a case–control study in Japan

    International Nuclear Information System (INIS)

    Lin, Yingsong; Kikuchi, Shogo; Ueda, Junko; Yagyu, Kiyoko; Ishii, Hiroshi; Ueno, Makoto; Egawa, Naoto; Nakao, Haruhisa; Mori, Mitsuru; Matsuo, Keitaro

    2013-01-01

    It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk. We conducted a hospital-based case–control study in Japan to investigate whether genetic variations in the FTO gene were associated with pancreatic cancer risk. We genotyped rs9939609 in the FTO gene of 360 cases and 400 control subjects. An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between rs9939609 and pancreatic cancer risk. The minor allele frequency of rs9939609 was 0.18 among control subjects. BMI was not associated with pancreatic cancer risk. Compared with individuals with the common homozygous TT genotype, those with the heterozygous TA genotype and the minor homozygous AA genotype had a 48% (OR=1.48; 95%CI: 1.07–2.04), and 66% increased risk (OR=1.66; 95%CI: 0.70–3.90), respectively, of pancreatic cancer after adjustment for sex, age, body mass index, cigarette smoking and history of diabetes. The per-allele OR was 1.41 (95%CI: 1.07–1.85). There were no significant interactions between TA/AA genotypes and body mass index. Our findings indicate that rs9939609 in the FTO gene is associated with pancreatic cancer risk in Japanese subjects, possibly through a mechanism that is independent of obesity. Further investigation and replication of our results is required in other independent samples

  19. Genome-wide association study of CSF levels of 59 alzheimer's disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation.

    Science.gov (United States)

    Kauwe, John S K; Bailey, Matthew H; Ridge, Perry G; Perry, Rachel; Wadsworth, Mark E; Hoyt, Kaitlyn L; Staley, Lyndsay A; Karch, Celeste M; Harari, Oscar; Cruchaga, Carlos; Ainscough, Benjamin J; Bales, Kelly; Pickering, Eve H; Bertelsen, Sarah; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M

    2014-10-01

    Cerebrospinal fluid (CSF) 42 amino acid species of amyloid beta (Aβ42) and tau levels are strongly correlated with the presence of Alzheimer's disease (AD) neuropathology including amyloid plaques and neurodegeneration and have been successfully used as endophenotypes for genetic studies of AD. Additional CSF analytes may also serve as useful endophenotypes that capture other aspects of AD pathophysiology. Here we have conducted a genome-wide association study of CSF levels of 59 AD-related analytes. All analytes were measured using the Rules Based Medicine Human DiscoveryMAP Panel, which includes analytes relevant to several disease-related processes. Data from two independently collected and measured datasets, the Knight Alzheimer's Disease Research Center (ADRC) and Alzheimer's Disease Neuroimaging Initiative (ADNI), were analyzed separately, and combined results were obtained using meta-analysis. We identified genetic associations with CSF levels of 5 proteins (Angiotensin-converting enzyme (ACE), Chemokine (C-C motif) ligand 2 (CCL2), Chemokine (C-C motif) ligand 4 (CCL4), Interleukin 6 receptor (IL6R) and Matrix metalloproteinase-3 (MMP3)) with study-wide significant p-values (pprocessing and pro-inflammatory signaling. SNPs associated with ACE, IL6R and MMP3 protein levels are located within the coding regions of the corresponding structural gene. The SNPs associated with CSF levels of CCL4 and CCL2 are located in known chemokine binding proteins. The genetic associations reported here are novel and suggest mechanisms for genetic control of CSF and plasma levels of these disease-related proteins. Significant SNPs in ACE and MMP3 also showed association with AD risk. Our findings suggest that these proteins/pathways may be valuable therapeutic targets for AD. Robust associations in cognitively normal individuals suggest that these SNPs also influence regulation of these proteins more generally and may therefore be relevant to other diseases.

  20. Chelsea, Pimlico and Belgravia District Nursing Association 1930-1939::A case study

    OpenAIRE

    Bliss, Julie

    2017-01-01

    The case study explores how the expansion of the health services during the interwar period impacted upon the status of district nursing and examines how being a voluntary service shaped district nursing associations. A range of primary sources were used; the Association Annual Reports, the Medical Officer for Health Annual Reports for the Borough of Chelsea, the Ministry of Health records, the archives of the Queen's Nursing Institute (QNI) and the Borough of Chelsea Council Minutes.The Medi...

  1. Physical Activity, Study Sitting Time, Leisure Sitting Time, and Sleep Time Are Differently Associated With Obesity in Korean Adolescents: A Population-Based Study.

    Science.gov (United States)

    Kong, Il Gyu; Lee, Hyo-Jeong; Kim, So Young; Sim, Songyong; Choi, Hyo Geun

    2015-11-01

    Low physical activity, long leisure sitting time, and short sleep time are risk factors for obesity, but the association with study sitting time is unknown. The objective of this study was to evaluate the association between these factors and obesity.We analyzed the association between physical activity, study sitting time, leisure sitting time, and sleep time and subject weight (underweight, healthy weight, overweight, and obese), using data from a large population-based survey, the 2013 Korea Youth Risk Behavior Web-based Survey. Data from 53,769 participants were analyzed using multinomial logistic regression analyses with complex sampling. Age, sex, region of residence, economic level, smoking, stress level, physical activity, sitting time for study, sitting time for leisure, and sleep time were adjusted as the confounders.Low physical activity (adjusted odds ratios [AORs] = 1.03, 1.12) and long leisure sitting time (AORs = 1.15, 1.32) were positively associated with overweight and obese. Low physical activity (AOR = 1.33) and long leisure sitting time (AOR = 1.12) were also associated with underweight. Study sitting time was negatively associated with underweight (AOR = 0.86) but was unrelated to overweight (AOR = 0.97, 95% confidence interval [CI] = 0.91-1.03) and obese (AOR = 0.94, 95% CI = 0.84-1.04). Sleep time (physical activity, decreasing leisure sitting time, and obtaining sufficient sleep would be beneficial in maintaining a healthy weight. However, study sitting time was not associated with overweight or obese.

  2. Older Adults Show Deficits in Retrieving and Decoding Associative Mediators Generated at Study

    Science.gov (United States)

    Hertzog, Christopher; Fulton, Erika K.; Mandviwala, Lulua; Dunlosky, John

    2013-01-01

    We instructed the use of mediators to encode paired-associate items, and then measured both cued recall of targets and mediators. Older adults (n = 49) and younger adults (n = 57) studied a mixed list of concrete and abstract noun pairs under instructions to either generate a sentence or an image to form a new association between normatively…

  3. Hormone replacement therapy is associated with gastro-oesophageal reflux disease: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Close Helen

    2012-05-01

    Full Text Available Abstract Background Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT. Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. Methods 51,182 menopausal women were identified using the UK General Practice Research Database between 1995–2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs were calculated for GORD and proton-pump inhibitor (PPI use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. Results In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18–1.89. Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03–1.74. Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01–2.22. Conclusions This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance.

  4. Spectroscopic study of the Scorpio-Centaurus association

    Energy Technology Data Exchange (ETDEWEB)

    Rajamohan, R [Indian Inst. of Astrophysics, Bangalore

    1976-09-01

    Rotational velocities as well as hydrogen and helium line intensities of one hundred and twelve members of the Scorpio-Centaurus association have been derived. For stars with Msub(v)<0.0, the distribution of rotational velocities of both the upper Scorpius subgroup and the upper Centaurus-Lupus subgroup are similar and closely resemble those of the field stars. Stars with Msub(v)>0.0, all of which are found in the dense upper Scorpius region, rotate much faster than their counter-parts amongst field stars, the Pleiades and Alpha-Persei cluster members. The measured equivalent width of H for 77 stars provide a distance modulus of 6.0 +- 0.09 magnitudes for the association. Evolutionary effects in the derived hydrogen line intensities are found between the two subgroups. The hydrogen-line intensities at all spectral types in the upper Centaurus-Lupus subgroup are systematically smaller than those of members in the upper Scorpius subgroup. Analysis of high dispersion spectra of five members of the association yield a helium abundance of Nsub(He)/Nsub(H) = 0.096 +- 0.004. Along with data available in the literature, the mean helium abundance of thirteen stars of this association if found to be 0.098 +- 0.004 by number. For the two main subgroups of this association, a value of 0.105 +- 0.001 is derived for the upper Scorpius group from three stars and 0.096 +- 0.005 for the upper Scorpius group from ten stars. Within the capabilities of the present methods, there seems to be no difference between the two subgroups as far as rotational velocities and initial helium abundance are concerned, a fact that must be borne in mind in the interpretation of the difference found between the two subgroups from photoelectric photometry.

  5. Association Between the Mediterranean Diet and Cancer Risk: A Review of Observational Studies

    NARCIS (Netherlands)

    Verberne, L.D.M.; Bach-Faig, A.; Buckland, G.; Serra-Majem, L.

    2010-01-01

    The aim of this article was to summarize the evidence concerning the association between Mediterranean dietary pattern and cancer risk in observational epidemiological studies. All the studies that met the following criteria were reviewed: human cohort and case-control studies that examined the

  6. The association between stress and headache: A longitudinal population-based study.

    Science.gov (United States)

    Schramm, Sara H; Moebus, Susanne; Lehmann, Nils; Galli, Ursula; Obermann, Mark; Bock, Eva; Yoon, Min-Suk; Diener, Hans-Christoph; Katsarava, Zaza

    2015-09-01

    We studied the association between stress intensity and headache frequency for tension-type headache (TTH), migraine and migraine with coexisting TTH (MigTTH). We studied a population-based sample of 5159 participants (21-71 years) who were asked quarterly between March 2010 and April 2012 about headache and stress. Log-linear regression in the framework of generalized estimating equations was used to estimate regression coefficients presented as percent changes to describe the association between stress intensity (modified visual analog scale (VAS) from 0 to 100) and headache frequency (days/month) stratified by headache subtypes and age groups and adjusted for sex, age, frequent intake of acute pain drugs, drinking, smoking, BMI and education. TTH was reported in 31% participants (48.1 ± 12.5years, 51.5% women, 2.2 ± 3.9 mean headache days/month, 52.3 ± 26.7 mean stress), migraine in 14% (44.8 ± 11.3years, 73.3%, 4.5 ± 5.2 days/month, 62.4 ± 23.3), MigTTH in 10.6% (43.5 ± 11.5 years, 61.0%, 3.6 ± 4.8 days/month, 58.6 ± 24.1), 23.6% were unclassifiable, and 20.8% had no headache. In participants with TTH an increase of 10 points on VAS was associated with an increase of headaches days/month of 6.0% (adjusted). Higher effects were observed in younger age groups (21-30/31-40/41-50/51-60/61-71 years: 9.8/10.2/7.0/6.5/3.5%). Slightly lower effects were observed for migraine (4.3%, 8.1/5.1/3.4/6.3/0.3%) and MigTTH (4.2%, 5.5/6.8/6.9/5.8/-0.7%). Our study provides evidence for an association between stress intensity and headache frequency. © International Headache Society 2014.

  7. Review article: Associations between Helicobacter pylori and obesity--an ecological study.

    Science.gov (United States)

    Lender, N; Talley, N J; Enck, P; Haag, S; Zipfel, S; Morrison, M; Holtmann, G J

    2014-07-01

    There is emerging debate over the effect of Helicobacter pylori infection on body mass index (BMI). A recent study demonstrated that individuals who underwent H. pylori eradication developed significant weight gain as compared to subjects with untreated H. pylori colonisation. To elucidate the association between H. pylori colonisation and the prevalence of overweight and obesity in developed countries. The literature was searched for publications reporting data on H. pylori prevalence rates and obesity prevalence rates. Studies selected reported H. pylori prevalence in random population samples with sample sizes of more than 100 subjects in developed countries (GDP >25,000 US$/person/year). Corresponding BMI distributions for corresponding countries and regions were identified. Nonparametric tests were used to compare the association between H. pylori and overweight and obesity rates. Forty-nine studies with data from 10 European countries, Japan, the US and Australia were identified. The mean H. pylori rate was 44.1% (range 17-75%), the mean rates for obesity and overweight were 46.6 (± 16)% and 14.2 (± 8.9)%. The rate of obesity and overweight were inversely and significantly (r = 0.29, P < 0.001) correlated with the prevalence of H. pylori infection. There is an inverse correlation between H. pylori prevalence and rate of overweight/obesity in countries of the developed world. Thus, the gradual decrease of the H. pylori colonisation that has been observed in recent decades (or factors associated with decrease of) could be causally related to the obesity endemic observed in the Western world. © 2014 John Wiley & Sons Ltd.

  8. Association between smoking habits and acne vulgaris. A case-control study

    Directory of Open Access Journals (Sweden)

    Alice Mannocci

    2012-09-01

    Full Text Available

    Background: acne vulgaris, is one of the most common skin disorder. Previous studies about the role of smoke in the pathogenesis of acne reported contradictory results. The aim of this study was to conduct a case-control study investigating the relationship between tobacco smoking and acne.

    Methods: a case-control study was performed during the period September 2009 - February 2010. A questionnaire was administrated to each participant, to assess the association acne - smoke. Cases were outpatients of the Dermatologic Ambulatory of the “Fiorini” Hospital, Sapienza University of Rome (Italy. Controls were age and gender-matched to the cases. The ratio cases-controls was 1:2. A univariate and a multiple logistic regression analysis were conducted; Odds Ratio (OR and the relative 95% confidence interval (95%CI were assessed. The statistical significance was set at p < 0.05.

    Results: crude OR for the association acne - smoke was 7.26 (IC=2.27-23.18; adjusted OR for sex and age was 5.47 (IC=1.67-17.97. Of 93 cases, 6 had a severe grade of acne (6.5%, 19 had an intermediate grade of acne (20.4%, and 68 had a mild grade of acne (73.1%. No one of the smokers had a severe grade of acne, one had an intermediate grade of acne and 11 had mild acne; these differences are not statistically significant.

    Conclusions: the association between acne and smoke shows an increased risk (OR=7.26 with a statistically significant CI. Moreover, people ≥ 18 years of age have twice the risk compared to persons < 18 years of age (OR=2.31.

  9. Cat scratches, not bites, are associated with unipolar depression--cross-sectional study.

    Science.gov (United States)

    Flegr, Jaroslav; Hodný, Zdeněk

    2016-01-05

    A recent study performed on 1.3 million patients showed a strong association between being bitten by a cat and probability of being diagnosed with depression. Authors suggested that infection with cat parasite Toxoplasma could be the reason for this association. A cross sectional internet study on a non-clinical population of 5,535 subjects was undertaken. The subjects that reported having been bitten by a dog and a cat or scratched by a cat have higher Beck depression score. They were more likely to have visited psychiatrists, psychotherapists and neurologists in past two years, to have been previously diagnosed with depression (but not with bipolar disorder). Multivariate analysis of models with cat biting, cat scratching, toxoplasmosis, the number of cats at home, and the age of subjects as independent variables showed that only cat scratching had positive effect on depression (p = 0.004). Cat biting and toxoplasmosis had no effect on the depression, and the number of cats at home had a negative effect on depression (p = 0.021). Absence of association between toxoplasmosis and depression and five times stronger association of depression with cat scratching than with cat biting suggests that the pathogen responsible for mood disorders in animals-injured subjects is probably not the protozoon Toxoplasma gondii but another organism; possibly the agent of cat-scratched disease - the bacteria Bartonella henselae.

  10. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study

    NARCIS (Netherlands)

    Surawicz, C. M.; Elmer, G. W.; Speelman, P.; McFarland, L. V.; Chinn, J.; van Belle, G.

    1989-01-01

    Saccharomyces boulardii, a nonpathogenic yeast, has been widely used in Europe to prevent antibiotic-associated diarrhea (AAD). We performed a prospective double-blind controlled study to investigate AAD in hospitalized patients and to evaluate the effect of S. boulardii, a living yeast, given in

  11. [Statin associated myopathy in clinical practice. Results of DAMA study].

    Science.gov (United States)

    Millán, Jesús; Pedro-Botet, Juan; Climent, Elisenda; Millán, Joaquín; Rius, Joan

    Muscle symptoms, with or without elevation of creatin kinase are one of the main adverse effects of statin therapy, a fact that sometimes limits their use. The aim of this study was to evaluate the clinical characteristics of patients treated with statins who have complained muscle symptoms and to identify possible predictive factors. A cross-sectional one-visit, non-interventional, national multicenter study including patients of both sexes over 18 years of age referred for past or present muscle symptoms associated with statin therapy was conducted. 3,845 patients were recruited from a one-day record from 2,001 physicians. Myalgia was present in 78.2% of patients included in the study, myositis in 19.3%, and rhabdomyolysis in 2.5%. Patients reported muscle pain in 77.5% of statin-treated individuals, general weakness 42.7%, and cramps 28.1%. Kidney failure, intense physical exercise, alcohol consumption (>30g/d in men and 20g/d in women) and abdominal obesity were the clinical situations associated with statin myopathy. Myalgia followed by myositis are the most frequent statin-related side effects. It should be recommended control environmental factors such as intense exercise and alcohol intake as well as abdominal obesity and renal function of the patient treated with statins. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. 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.

  13. Using incomplete trios to boost confidence in family based association studies

    Directory of Open Access Journals (Sweden)

    Varsha eDhankani

    2016-03-01

    Full Text Available Most currently available family based association tests are designed to account only for nuclear families with complete genotypes for parents as well as offspring. Due to the availability of increasingly less expensive generation of whole genome sequencing information, genetic studies are able to collect data for more families and from large family cohorts with the goal of improving statistical power. However, due to missing genotypes, many families are not included in the family based association tests, negating the benefits of large scale sequencing data. Here, we present the CIFBAT method to use incomplete families in Family Based Association Test (FBAT to evaluate robustness against missing data. CIFBAT uses quantile intervals of the FBAT statistic by randomly choosing valid completions of incomplete family genotypes based on Mendelian inheritance rules. By considering all valid completions equally likely and computing quantile intervals over several randomized iterations, CIFBAT avoids assumption of a homogeneous population structure or any particular missingness pattern in the data. Using simulated data, we show that the quantile intervals computed by CIFBAT are useful in validating robustness of the FBAT statistic against missing data and in identifying genomic markers with higher precision. We also propose a novel set of candidate genomic markers for uterine related abnormalities from analysis of familial whole genome sequences, and provide validation for a previously established set of candidate markers for Type 1 diabetes. We have provided a software package that incorporates TDT, robustTDT, FBAT and CIFBAT. The data format proposed for the software uses half the memory space that the standard FBAT format (PED files use, making it efficient for large scale genome wide association studies.

  14. Associations Between the Macroeconomic Indicators and Suicide Rates in India: Two Ecological Studies.

    Science.gov (United States)

    Rajkumar, Anto P; Senthilkumar, P; Gayathri, K; Shyamsundar, G; Jacob, K S

    2015-01-01

    While western studies have focused on the importance of psychiatric illnesses in the complex pathways leading to suicides, several Indian studies have highlighted the important contributions by economic, social, and cultural factors. Hence, we tested the hypothesis that annual national suicide rates and suicide rates of the different states in India were associated with macroeconomic indices. Data from the National crime records bureau, Ministry of finance, labour bureau, Government of India, population commission, and planning commission official portals, World Bank and the United Nations were accessed. We assessed the correlations of annual national and state-wise suicide rates with macroeconomic, health, and other indices using ecological study design for India, and for its different states and union territories. We documented statistically significant associations between the suicide rates and per capita gross domestic product, consumer price index, foreign exchange, trade balance, total health expenditure as well as literacy rates. As recent economic growth in India is associated with increasing suicide rates, macroeconomic policies emphasizing equitable distribution of resources may help curtailing the population suicide rates in India.

  15. Lifestyles Associated With Human Semen Quality: Results From MARHCS Cohort Study in Chongqing, China

    Science.gov (United States)

    Yang, Huan; Chen, Qing; Zhou, Niya; Sun, Lei; Bao, Huaqiong; Tan, Lu; Chen, Hongqiang; Zhang, Guowei; Ling, Xi; Huang, Linping; Li, Lianbing; Ma, Mingfu; Yang, Hao; Wang, Xiaogang; Zou, Peng; Peng, Kaige; Liu, Kaijun; Liu, Taixiu; Cui, Zhihong; Liu, Jinyi; Ao, Lin; Zhou, Ziyuan; Cao, Jia

    2015-01-01

    Abstract Decline of semen quality in past decades is suggested to be potentially associated with environmental and sociopsychobehavioral factors, but data from population-based cohort studies is limited. The male reproductive health in Chongqing College students (MARHCS) study was established in June 2013 as a perspective cohort study that recruited voluntary male healthy college students from 3 universities in Chongqing. The primary objectives of the MARHCS study are to investigate the associations of male reproductive health in young adults with sociopsychobehavioral factors, as well as changes of environmental exposure due to the relocation from rural campus (in University Town) to metro-campus (in central downtown). A 93-item questionnaire was used to collect sociopsychobehavioral information in manner of interviewer–interviewing, and blood, urine and semen samples were collected at the same time. The study was initiated with 796 healthy young men screened from 872 participants, with a median age of 20. About 81.8% of this population met the WHO 2010 criteria on semen quality given to the 6 routine parameters. Decreases of 12.7%, 19.8%, and 17.0%, and decreases of 7.7%, 17.6%, and 14.7% in total sperm count and sperm concentration, respectively, were found to be associated with the tertiles of accumulated smoking amount. Fried food consumption (1–2 times/wk or ≥3 times/wk vs nonconsumers) was found to be associated with decreased total sperm count (10.2% or 24.5%) and sperm concentration (13.7% or 17.2%), respectively. Coffee consumption was found to be associated with increased progressive and nonprogressive motility of 8.9% or 15.4% for subjects consuming 1–2 cups/wk or ≥3 cups/wk of coffee, respectively. Cola consumption appeared an association with decreased semen volume at 4.1% or 12.5% for 1–2 bottles/wk or ≥3 bottles/wk. A cohort to investigate the effects of environmental/sociopsychobehavioral factors act on semen quality was

  16. Family Stigma Associated With Epilepsy: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Reza nabi amjad

    2017-03-01

    Full Text Available Introduction: Harmful nature of epilepsy can affect the patient and their parent. Stigma, arising from it, affects the patient and their family. To relieve it understanding the experiences of the parent are useful. This study was aimed at understanding the experiences of parent of child with epilepsy in Iran. Methods: In this interpretative phenomenological study, 10 parents who took care of their child with epilepsy were participated. Data were collected through in-depth semi-structured interviews. After transcription, data were analyzed using Van Manen’s method. Results: Family stigma emerged as a main theme in data analysis with three subthemes including becoming verbally abusive, a dull and heavy shadowed look, and associates interference. Conclusion: Family stigma is a major challenge for parents of child with epilepsy need to special attention by health system. Nurses, as a big part of the system, can play an important role to manage this problem.

  17. Candidate gene association studies in syndromic and non-syndromic cleft lip and palate

    Energy Technology Data Exchange (ETDEWEB)

    Daack-Hirsch, S.; Basart, A.; Frischmeyer, P. [Univ. of Iowa, IA (United States)] [and others

    1994-09-01

    Using ongoing case ascertainment through a birth defects registry, we have collected 219 nuclear families with non-syndromic cleft lip and/or palate and 111 families with a collection of syndromic forms. Syndromic cases include 24 with recognized forms and 72 with unrecognized syndromes. Candidate gene studies as well as genome-wide searches for evidence of microdeletions and isodisomy are currently being carried out. Candidate gene association studies, to date, have made use of PCR-based polymorphisms for TGFA, MSX1, CLPG13 (a CA repeat associated with a human homologue of a locus that results in craniofacial dysmorphogenesis in the mouse) and an STRP found in a Van der Woude syndrome microdeletion. Control tetranucleotide repeats, which insure that population-based differences are not responsible for any observed associations, are also tested. Studies of the syndromic cases have included the same list of candidate genes searching for evidence of microdeletions and a genome-wide search using tri- and tetranucleotide polymorphic markers to search for isodisomy or structural rearrangements. Significant associations have previously been identified for TGFA, and, in this report, identified for MSX1 and nonsyndromic cleft palate only (p = 0.04, uncorrected). Preliminary results of the genome-wide scan for isodisomy has returned no true positives and there has been no evidence for microdeletion cases.

  18. Office type's association to employees' welfare: Three studies.

    Science.gov (United States)

    Danielsson, Christina Bodin

    2016-08-12

    The workplace is important for employees' daily life and well-being. This article investigates exploratory the office design's role for employees' welfare from different perspectives. By comparing different studies of the office, type's influence on different factors of employees' welfare the aim is to see if any common patterns exist in office design's impact. The three included studies investigate office type's association with employees' welfare by measuring its influence on: a) perception of leadership, b) sick leave, and c) job satisfaction.The sample consists of office employees from a large, national representative work environment survey that work in one of the seven identified office types in contemporary office design: (1) cell-offices; (2) shared-room offices; (3) small, (4) medium-sized and (5) large open-plan offices; (6) flex-offices and (7) combi-offices. Statistical method used is multivariate logistic and linear regression analysis with adjustment for background factors. Overall results show that shared-room office, traditional open plan offices and flex-office stand out negatively, but to different degree(s) on the different outcomes measured. This explorative comparison of different studies finds a pattern of office types that repeatedly show indications of negative influence on employees' welfare, but further studies are needed to clarify this.

  19. An information-gain approach to detecting three-way epistatic interactions in genetic association studies

    DEFF Research Database (Denmark)

    Hu, Ting; Chen, Yuanzhu; Kiralis, Jeff W

    2013-01-01

    Background Epistasis has been historically used to describe the phenomenon that the effect of a given gene on a phenotype can be dependent on one or more other genes, and is an essential element for understanding the association between genetic and phenotypic variations. Quantifying epistasis......-way epistasis. Methods Such a measure is based on information gain, and is able to separate all lower order effects from pure three-way epistasis. Results Our method was verified on synthetic data and applied to real data from a candidate-gene study of tuberculosis in a West African population....... In the tuberculosis data, we found a statistically significant pure three-way epistatic interaction effect that was stronger than any lower-order associations. Conclusion Our study provides a methodological basis for detecting and characterizing high-order gene-gene interactions in genetic association studies....

  20. Genome-wide association study identifies novel breast cancer susceptibility loci

    Science.gov (United States)

    Easton, Douglas F.; Pooley, Karen A.; Dunning, Alison M.; Pharoah, Paul D. P.; Thompson, Deborah; Ballinger, Dennis G.; Struewing, Jeffery P.; Morrison, Jonathan; Field, Helen; Luben, Robert; Wareham, Nicholas; Ahmed, Shahana; Healey, Catherine S.; Bowman, Richard; Meyer, Kerstin B.; Haiman, Christopher A.; Kolonel, Laurence K.; Henderson, Brian E.; Marchand, Loic Le; Brennan, Paul; Sangrajrang, Suleeporn; Gaborieau, Valerie; Odefrey, Fabrice; Shen, Chen-Yang; Wu, Pei-Ei; Wang, Hui-Chun; Eccles, Diana; Evans, D. Gareth; Peto, Julian; Fletcher, Olivia; Johnson, Nichola; Seal, Sheila; Stratton, Michael R.; Rahman, Nazneen; Chenevix-Trench, Georgia; Bojesen, Stig E.; Nordestgaard, Børge G.; Axelsson, Christen K.; Garcia-Closas, Montserrat; Brinton, Louise; Chanock, Stephen; Lissowska, Jolanta; Peplonska, Beata; Nevanlinna, Heli; Fagerholm, Rainer; Eerola, Hannaleena; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Hunter, David J.; Hankinson, Susan E.; Cox, David G.; Hall, Per; Wedren, Sara; Liu, Jianjun; Low, Yen-Ling; Bogdanova, Natalia; Schürmann, Peter; Dörk, Thilo; Tollenaar, Rob A. E. M.; Jacobi, Catharina E.; Devilee, Peter; Klijn, Jan G. M.; Sigurdson, Alice J.; Doody, Michele M.; Alexander, Bruce H.; Zhang, Jinghui; Cox, Angela; Brock, Ian W.; MacPherson, Gordon; Reed, Malcolm W. R.; Couch, Fergus J.; Goode, Ellen L.; Olson, Janet E.; Meijers-Heijboer, Hanne; van den Ouweland, Ans; Uitterlinden, André; Rivadeneira, Fernando; Milne, Roger L.; Ribas, Gloria; Gonzalez-Neira, Anna; Benitez, Javier; Hopper, John L.; McCredie, Margaret; Southey, Melissa; Giles, Graham G.; Schroen, Chris; Justenhoven, Christina; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana; Day, Nicholas E.; Cox, David R.; Ponder, Bruce A. J.; Luccarini, Craig; Conroy, Don; Shah, Mitul; Munday, Hannah; Jordan, Clare; Perkins, Barbara; West, Judy; Redman, Karen; Driver, Kristy; Aghmesheh, Morteza; Amor, David; Andrews, Lesley; Antill, Yoland; Armes, Jane; Armitage, Shane; Arnold, Leanne; Balleine, Rosemary; Begley, Glenn; Beilby, John; Bennett, Ian; Bennett, Barbara; Berry, Geoffrey; Blackburn, Anneke; Brennan, Meagan; Brown, Melissa; Buckley, Michael; Burke, Jo; Butow, Phyllis; Byron, Keith; Callen, David; Campbell, Ian; Chenevix-Trench, Georgia; Clarke, Christine; Colley, Alison; Cotton, Dick; Cui, Jisheng; Culling, Bronwyn; Cummings, Margaret; Dawson, Sarah-Jane; Dixon, Joanne; Dobrovic, Alexander; Dudding, Tracy; Edkins, Ted; Eisenbruch, Maurice; Farshid, Gelareh; Fawcett, Susan; Field, Michael; Firgaira, Frank; Fleming, Jean; Forbes, John; Friedlander, Michael; Gaff, Clara; Gardner, Mac; Gattas, Mike; George, Peter; Giles, Graham; Gill, Grantley; Goldblatt, Jack; Greening, Sian; Grist, Scott; Haan, Eric; Harris, Marion; Hart, Stewart; Hayward, Nick; Hopper, John; Humphrey, Evelyn; Jenkins, Mark; Jones, Alison; Kefford, Rick; Kirk, Judy; Kollias, James; Kovalenko, Sergey; Lakhani, Sunil; Leary, Jennifer; Lim, Jacqueline; Lindeman, Geoff; Lipton, Lara; Lobb, Liz; Maclurcan, Mariette; Mann, Graham; Marsh, Deborah; McCredie, Margaret; McKay, Michael; McLachlan, Sue Anne; Meiser, Bettina; Milne, Roger; Mitchell, Gillian; Newman, Beth; O'Loughlin, Imelda; Osborne, Richard; Peters, Lester; Phillips, Kelly; Price, Melanie; Reeve, Jeanne; Reeve, Tony; Richards, Robert; Rinehart, Gina; Robinson, Bridget; Rudzki, Barney; Salisbury, Elizabeth; Sambrook, Joe; Saunders, Christobel; Scott, Clare; Scott, Elizabeth; Scott, Rodney; Seshadri, Ram; Shelling, Andrew; Southey, Melissa; Spurdle, Amanda; Suthers, Graeme; Taylor, Donna; Tennant, Christopher; Thorne, Heather; Townshend, Sharron; Tucker, Kathy; Tyler, Janet; Venter, Deon; Visvader, Jane; Walpole, Ian; Ward, Robin; Waring, Paul; Warner, Bev; Warren, Graham; Watson, Elizabeth; Williams, Rachael; Wilson, Judy; Winship, Ingrid; Young, Mary Ann; Bowtell, David; Green, Adele; deFazio, Anna; Chenevix-Trench, Georgia; Gertig, Dorota; Webb, Penny

    2009-01-01

    Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2>0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P<10−7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P<0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. PMID:17529967

  1. Factors Associated with Atopy in Toddlers: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Jolene Yung

    2015-02-01

    Full Text Available In this case-control study the association between the approaches used to feed infants, together with known family and environmental factors, and the occurrence of atopic illness in toddlers between the ages of 4 months to 3 years in Hong Kong was examined. A total of 206 subjects were recruited from April to June of 2014. The results obtained by binary logistic regression indicated that atopy is associated with boys (OR 2.072, CI 1.089–3.941, the maternal use of antibiotics in utero or while breast feeding (OR 2.276, CI 1.151–4.504, the later commencement of mixed feeding (OR 2.497, CI 1.025–6.082, breast feeding exclusively for 3 months (OR 1.972, CI 1.009–3.857, and having a mother who was diagnosed with eczema (OR 4.510, CI 1.764–11.530. Although an exclusive reliance on breast feeding has been shown to be predictive of atopy among toddlers, the positive qualities of breast milk cannot be ignored. A further study of the contents and nutritional values of breast milk is warranted.

  2. A Monte Carlo simulation study of associated liquid crystals

    Science.gov (United States)

    Berardi, R.; Fehervari, M.; Zannoni, C.

    We have performed a Monte Carlo simulation study of a system of ellipsoidal particles with donor-acceptor sites modelling complementary hydrogen-bonding groups in real molecules. We have considered elongated Gay-Berne particles with terminal interaction sites allowing particles to associate and form dimers. The changes in the phase transitions and in the molecular organization and the interplay between orientational ordering and dimer formation are discussed. Particle flip and dimer moves have been used to increase the convergency rate of the Monte Carlo (MC) Markov chain.

  3. Genome-wide association study identifies polymorphisms associated with the analgesic effect of fentanyl in the preoperative cold pressor-induced pain test

    Directory of Open Access Journals (Sweden)

    Kaori Takahashi

    2018-03-01

    Full Text Available Opioid analgesics are widely used for the treatment of moderate to severe pain. The analgesic effects of opioids are well known to vary among individuals. The present study focused on the genetic factors that are associated with interindividual differences in pain and opioid sensitivity. We conducted a multistage genome-wide association study in subjects who were scheduled to undergo mandibular sagittal split ramus osteotomy and were not medicated until they received fentanyl for the induction of anesthesia. We preoperatively conducted the cold pressor-induced pain test before and after fentanyl administration. The rs13093031 and rs12633508 single-nucleotide polymorphisms (SNPs near the LOC728432 gene region and rs6961071 SNP in the tcag7.1213 gene region were significantly associated with the analgesic effect of fentanyl, based on differences in pain perception latency before and after fentanyl administration. The associations of these three SNPs that were identified in our exploratory study have not been previously reported. The two polymorphic loci (rs13093031 and rs12633508 were shown to be in strong linkage disequilibrium. Subjects with the G/G genotype of the rs13093031 and rs6961071 SNPs presented lower fentanyl-induced analgesia. Our findings provide a basis for investigating genetics-based analgesic sensitivity and personalized pain control. Keywords: Opioid sensitivity, Analgesia, Fentanyl, Polymorphism, GWAS

  4. Epigenome-wide association study of DNA methylation in narcolepsy: an integrated genetic and epigenetic approach.

    Science.gov (United States)

    Shimada, Mihoko; Miyagawa, Taku; Toyoda, Hiromi; Tokunaga, Katsushi; Honda, Makoto

    2018-04-01

    Narcolepsy with cataplexy, which is a hypersomnia characterized by excessive daytime sleepiness and cataplexy, is a multifactorial disease caused by both genetic and environmental factors. Several genetic factors including HLA-DQB1*06:02 have been identified; however, the disease etiology is still unclear. Epigenetic modifications, such as DNA methylation, have been suggested to play an important role in the pathogenesis of complex diseases. Here, we examined DNA methylation profiles of blood samples from narcolepsy and healthy control individuals and performed an epigenome-wide association study (EWAS) to investigate methylation loci associated with narcolepsy. Moreover, data from the EWAS and a previously performed narcolepsy genome-wide association study were integrated to search for methylation loci with causal links to the disease. We found that (1) genes annotated to the top-ranked differentially methylated positions (DMPs) in narcolepsy were associated with pathways of hormone secretion and monocarboxylic acid metabolism. (2) Top-ranked narcolepsy-associated DMPs were significantly more abundant in non-CpG island regions and more than 95 per cent of such sites were hypomethylated in narcolepsy patients. (3) The integrative analysis identified the CCR3 region where both a single methylation site and multiple single-nucleotide polymorphisms were found to be associated with the disease as a candidate region responsible for narcolepsy. The findings of this study suggest the importance of future replication studies, using methylation technologies with wider genome coverage and/or larger number of samples, to confirm and expand on these results.

  5. Human CLOCK gene-associated attention deficit hyperactivity disorder-related features in healthy adults: quantitative association study using Wender Utah Rating Scale.

    Science.gov (United States)

    Jeong, Seong Hoon; Yu, Je-Chun; Lee, Chang Hwa; Choi, Kyeong-Sook; Choi, Jung-Eun; Kim, Se Hyun; Joo, Eun-Jeong

    2014-02-01

    Circadian rhythm disturbance is highly prevalent in attention deficit hyperactivity disorder (ADHD). Recently, the association between the CLOCK gene and ADHD has been demonstrated in clinical samples, and the CLOCK gene's role was thought to be mediated by rhythm dysregulation. Meanwhile, ADHD has been suggested as the extreme end of a continuously distributed trait that can be found in the general population. Therefore, we examined two possibilities: (1) an ADHD-related continuous trait may be associated with the CLOCK gene, and (2) this association may be mediated by the degree of individuals' evening preference. To explore these possibilities, we performed a quantitative trait locus association study with a sample of 1,289 healthy adults. The Wender Utah Rating Scale (WURS) and the Composite Scale of Morningness (CSM) were utilized to measure the quantitative traits. Quantitative association analysis was performed using PLINK software. We found that rs1801260 (=T3111C) was associated with WURS scores in both allele-wise (p = 0.018) and haplotype-wise analyses (range of p values: 0.0155-0.0171) in male participants only. After controlling for the CSM total score as a covariate, the strength of the association did not change at all, suggesting that the association was not mediated by evening preference. Despite the very weak association signal, our results provide evidence that the CLOCK gene's association with ADHD in clinical samples may be generalizable to traits measured in the normal population. However, as our results failed to show a mediating role of evening preference, ongoing efforts are needed to identify the mechanisms by which the CLOCK gene determines ADHD-related traits.

  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 study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals

    DEFF Research Database (Denmark)

    Soerensen, Mette; Nygaard, Marianne; Dato, Serena

    2015-01-01

    -old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease......FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 oldest...... borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94-100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis...

  8. Study of a PEFC power generator modular architecture based on a multi-stack association

    Energy Technology Data Exchange (ETDEWEB)

    Garnier, James; Pera, Marie-Cecile; Hissel, Daniel; Kauffmann, Jean-Marie [Laboratoire d' Electronique, Electrotechnique et Systemes, Unite Mixte de Recherche UTBM et UFC, L2ES-UTBM Batiment F-Technopole, Rue Thierry Mieg, 90010 Belfort (France); De Bernardinis, Alexandre; Candusso, Denis; Coquery, Gerard [Institut National de Recherche Sur Les Transports et Leur Securite (INRETS LTN), 2 Avenue Du General Malleret-Joinville, 94114 Arcueil (France)

    2006-05-19

    This paper presents a study of a polymer electrolyte fuel cell (PEFC) power generator based on a multi-stack association dedicated to transportation applications. First, a dynamic model of the fuel cell for high frequencies, which can be used in association with the power converter is presented. In a second hand, an original power converter architecture has been studied which authorizes the electrical association of two fuel cell stacks. Such a configuration is well adapted for the testing of fuel cell in normal or degraded mode which corresponds to real operating conditions encountered on-board a vehicle. Finally, simulation results of the complete twin-stacks power system are presented and discussed. (author)

  9. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

    Science.gov (United States)

    Zhang, Shujun

    2018-01-01

    Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

  10. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Xingjie Hao

    2018-01-01

    Full Text Available Genome-wide association studies (GWASs have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART. With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study.

  11. Community-Associated Methicillin-Resistant Staphylococcus aureus Case Studies

    Science.gov (United States)

    Sowash, Madeleine G.; Uhlemann, Anne-Catrin

    2014-01-01

    Over the past decade, the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the landscape of S. aureus infections around the globe. Initially recognized for its ability to cause disease in young and healthy individuals without healthcare exposures as well as for its distinct genotype and phenotype, this original description no longer fully encompasses the diversity of CA-MRSA as it continues to expand its niche. Using four case studies, we highlight a wide range of the clinical presentations and challenges of CA-MRSA. Based on these cases we further explore the globally polygenetic background of CA-MRSA with a special emphasis on generally less characterized populations. PMID:24085688

  12. Is open-angle glaucoma associated with early menopause? The Rotterdam Study

    NARCIS (Netherlands)

    Hulsman, C. A.; Westendorp, I. C.; Ramrattan, R. S.; Wolfs, R. C.; Witteman, J. C.; Vingerling, J. R.; Hofman, A.; de Jong, P. T.

    2001-01-01

    The authors examined the association between age at menopause and open-angle glaucoma among women aged > or = 55 years in the population-based Rotterdam Study (1990--1993). Information on age and type of menopause was obtained by interview. Subjects (n = 3,078) were stratified into three categories

  13. Frontotemporal dementia and its subtypes: a genome-wide association study.

    Science.gov (United States)

    Ferrari, Raffaele; Hernandez, Dena G; Nalls, Michael A; Rohrer, Jonathan D; Ramasamy, Adaikalavan; Kwok, John B J; Dobson-Stone, Carol; Brooks, William S; Schofield, Peter R; Halliday, Glenda M; Hodges, John R; Piguet, Olivier; Bartley, Lauren; Thompson, Elizabeth; Haan, Eric; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Borroni, Barbara; Padovani, Alessandro; Cruchaga, Carlos; Cairns, Nigel J; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Forloni, Gianluigi; Galimberti, Daniela; Fenoglio, Chiara; Serpente, Maria; Scarpini, Elio; Clarimón, Jordi; Lleó, Alberto; Blesa, Rafael; Waldö, Maria Landqvist; Nilsson, Karin; Nilsson, Christer; Mackenzie, Ian R A; Hsiung, Ging-Yuek R; Mann, David M A; Grafman, Jordan; Morris, Christopher M; Attems, Johannes; Griffiths, Timothy D; McKeith, Ian G; Thomas, Alan J; Pietrini, P; Huey, Edward D; Wassermann, Eric M; Baborie, Atik; Jaros, Evelyn; Tierney, Michael C; Pastor, Pau; Razquin, Cristina; Ortega-Cubero, Sara; Alonso, Elena; Perneczky, Robert; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Kurz, Alexander; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Rogaeva, Ekaterina; St George-Hyslop, Peter; Rossi, Giacomina; Tagliavini, Fabrizio; Giaccone, Giorgio; Rowe, James B; Schlachetzki, Johannes C M; Uphill, James; Collinge, John; Mead, Simon; Danek, Adrian; Van Deerlin, Vivianna M; Grossman, Murray; Trojanowski, John Q; van der Zee, Julie; Deschamps, William; Van Langenhove, Tim; Cruts, Marc; Van Broeckhoven, Christine; Cappa, Stefano F; Le Ber, Isabelle; Hannequin, Didier; Golfier, Véronique; Vercelletto, Martine; Brice, Alexis; Nacmias, Benedetta; Sorbi, Sandro; Bagnoli, Silvia; Piaceri, Irene; Nielsen, Jørgen E; Hjermind, Lena E; Riemenschneider, Matthias; Mayhaus, Manuel; Ibach, Bernd; Gasparoni, Gilles; Pichler, Sabrina; Gu, Wei; Rossor, Martin N; Fox, Nick C; Warren, Jason D; Spillantini, Maria Grazia; Morris, Huw R; Rizzu, Patrizia; Heutink, Peter; Snowden, Julie S; Rollinson, Sara; Richardson, Anna; Gerhard, Alexander; Bruni, Amalia C; Maletta, Raffaele; Frangipane, Francesca; Cupidi, Chiara; Bernardi, Livia; Anfossi, Maria; Gallo, Maura; Conidi, Maria Elena; Smirne, Nicoletta; Rademakers, Rosa; Baker, Matt; Dickson, Dennis W; Graff-Radford, Neill R; Petersen, Ronald C; Knopman, David; Josephs, Keith A; Boeve, Bradley F; Parisi, Joseph E; Seeley, William W; Miller, Bruce L; Karydas, Anna M; Rosen, Howard; van Swieten, John C; Dopper, Elise G P; Seelaar, Harro; Pijnenburg, Yolande A L; Scheltens, Philip; Logroscino, Giancarlo; Capozzo, Rosa; Novelli, Valeria; Puca, Annibale A; Franceschi, Massimo; Postiglione, Alfredo; Milan, Graziella; Sorrentino, Paolo; Kristiansen, Mark; Chiang, Huei-Hsin; Graff, Caroline; Pasquier, Florence; Rollin, Adeline; Deramecourt, Vincent; Lebert, Florence; Kapogiannis, Dimitrios; Ferrucci, Luigi; Pickering-Brown, Stuart; Singleton, Andrew B; Hardy, John; Momeni, Parastoo

    2014-07-01

    Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72--have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10(-8)) single-nucleotide polymorphisms. We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10(-8)). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10(-8); odds ratio=1·204 [95% CI 1·11-1·30]), rs9268856 (p=5·51 × 10(-9); 0·809 [0·76-0·86]) and rs1980493 (p value=1·57 × 10(-8), 0·775 [0·69-0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10(-7); 0·814 [0·71-0·92]). Analysis of expression and methylation quantitative trait loci data

  14. Study clarifies associations between hypogonadism and health in aging men.

    Science.gov (United States)

    Amory, John K

    2012-11-01

    Tajar and colleagues present the associations between moderate and severe hypogonadism, symptoms of androgen deficiency and the prevelence of end-organ evidence of androgen deficency in 2966 older men in the European Male Aging Study. They find lower muscle mass, reduced bone mineral density, anemia, insulin resistence, metabolic syndrome and cardiovascular disease, with greater risks of these signs of androgen deficiency at lower serum testosterone concentrations.

  15. Genome-wide association study identifies candidate genes for male fertility traits in humans.

    Science.gov (United States)

    Kosova, Gülüm; Scott, Nicole M; Niederberger, Craig; Prins, Gail S; Ober, Carole

    2012-06-08

    Despite the fact that hundreds of genes are known to affect fertility in animal models, relatively little is known about genes that influence natural fertility in humans. To broadly survey genes contributing to variation in male fertility, we conducted a genome-wide association study (GWAS) of two fertility traits (family size and birth rate) in 269 married men who are members of a founder population of European descent that proscribes contraception and has large family sizes. Associations between ∼250,000 autosomal SNPs and the fertility traits were examined. A total of 41 SNPs with p ≤ 1 × 10(-4) for either trait were taken forward to a validation study of 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Nine (22%) of the SNPs associated with reduced fertility in the GWAS were also associated with one or more of the ten measures of reduced sperm quantity and/or function, yielding 27 associations with p values LRRC32, which encodes a latent transforming growth factor β (TGF-β) receptor on regulatory T cells. We suggest that mutations in these genes that are more severe may account for some of the unexplained infertility (or subfertility) in the general population. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Common variant of ALPK1 is not associated with gout: a replication study.

    Science.gov (United States)

    Chiba, Toshinori; Matsuo, Hirotaka; Sakiyama, Masayuki; Nakayama, Akiyoshi; Shimizu, Seiko; Wakai, Kenji; Suma, Shino; Nakashima, Hiroshi; Sakurai, Yutaka; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi

    2015-01-01

    Gout is one of the most kinds of common inflammatory arthritis as a consequence of hyperuricemia. Alpha-protein kinase 1 (ALPK1) gene locates in a gout-susceptibility locus on chromosome 4q21-31, and encodes ALPK1 protein which plays a pivotal role in the phosphorylation of myosin 1. In the previous genetic study of Taiwanese populations, 3 single nucleotide polymorphisms (SNPs), rs11726117, rs231247 and rs231253, in ALPK1 gene were reported to have a significant association with gout. However, no replication study has been performed to confirm this association. Therefore, we first conducted a replication study with clinically defined gout patients in a different population. Linkage disequilibrium (LD) analyzes of the 3 SNPs in ALPK1 revealed that these SNPs are in strong LD in a Japanese population. Among the 3 SNPs of ALPK1, rs11726117 (M861T) is the only missense SNP. Therefore, rs11726117 was genotyped in a Japanese population of 903 clinically defined gout cases and 1,302 controls, and was evaluated for a possible association with gout. The minor allele frequencies of rs11726117 were 0.26 and 0.25 in the case and control groups, respectively. The association analysis has not detected a significant association between rs11726117 and gout susceptibility in a Japanese population (p = 0.44). Because ABCG2, a major causative gene for gout, also locates in the gout-susceptibility locus on chromosome 4q, these findings suggest that among genes in a gout-susceptibility locus, not ALPK1 but ABCG2 could be important as a gout-susceptible gene.

  17. Incorporating Functional Genomic Information in Genetic Association Studies Using an Empirical Bayes Approach.

    Science.gov (United States)

    Spencer, Amy V; Cox, Angela; Lin, Wei-Yu; Easton, Douglas F; Michailidou, Kyriaki; Walters, Kevin

    2016-04-01

    There is a large amount of functional genetic data available, which can be used to inform fine-mapping association studies (in diseases with well-characterised disease pathways). Single nucleotide polymorphism (SNP) prioritization via Bayes factors is attractive because prior information can inform the effect size or the prior probability of causal association. This approach requires the specification of the effect size. If the information needed to estimate a priori the probability density for the effect sizes for causal SNPs in a genomic region isn't consistent or isn't available, then specifying a prior variance for the effect sizes is challenging. We propose both an empirical method to estimate this prior variance, and a coherent approach to using SNP-level functional data, to inform the prior probability of causal association. Through simulation we show that when ranking SNPs by our empirical Bayes factor in a fine-mapping study, the causal SNP rank is generally as high or higher than the rank using Bayes factors with other plausible values of the prior variance. Importantly, we also show that assigning SNP-specific prior probabilities of association based on expert prior functional knowledge of the disease mechanism can lead to improved causal SNPs ranks compared to ranking with identical prior probabilities of association. We demonstrate the use of our methods by applying the methods to the fine mapping of the CASP8 region of chromosome 2 using genotype data from the Collaborative Oncological Gene-Environment Study (COGS) Consortium. The data we analysed included approximately 46,000 breast cancer case and 43,000 healthy control samples. © 2016 The Authors. *Genetic Epidemiology published by Wiley Periodicals, Inc.

  18. Necrotizing Fasciitis Associated with Pregnancy: a Population-Based Cohort Study.

    Science.gov (United States)

    Oud, Lavi; Watkins, Phillip

    2014-12-01

    Necrotizing fasciitis (NF) is a rare complication in pregnant women. There have been no population-level data reported to date on its epidemiology, clinical features, resource utilization, and outcomes. This was a retrospective, population-based cohort study, using the Texas Inpatient Public Use Data File to identify pregnancy-associated hospitalizations for the years 2001-2010. Hospitalizations with a diagnosis of NF were then identified using the International Classification of Diseases, Ninth Revision, Clinical Modification code 728.86. Denominator data for incidence estimates were derived from the Texas Center for Health Statistics reports of live births, abortions and fetal deaths, and previously reported population-based, age-specific linkage data on miscarriage, and were used to estimate the annual total number of pregnancies (TEP). The incidence of pregnancy-associated NF (PANF), hospitalization type, clinical features, resource utilization and outcomes were examined. There were 4,060,201 pregnancy-associated hospitalizations and 148 PANF hospitalizations during study period. Postpartum hospitalizations accounted for 82.4% of all PANF events, and intensive care unit care was required in 61.5%. The key trends noted between 2001-2002 and 2009-2010 included rising incidence of PANF from 1.1 vs. 3.8 per 100,000 TEP-years (P = 0.0001), chronic comorbidities 0% vs. 31.7% (P = 0.0777), and development of organ failure in 9.1% vs. 31.7% (P = 0.0302). There was no significant change in total hospital charges or hospital length of stay. Three patients (2%) died in the hospital and 55% of survivors had routine home discharge. The present cohort of PANF is the largest reported to date. The incidence of PANF rose nearly 3.5-fold over the past decade, with most events developing following delivery hospitalization. Chronic illness has been increasingly present, along with rising severity of illness. The majority of patients required ICU care. Hospital mortality was

  19. 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

  20. Association between chronic kidney disease and urinary calculus by stone location: a population-based study.

    Science.gov (United States)

    Keller, Joseph J; Chen, Yi-Kuang; Lin, Herng-Ching

    2012-12-01

    Study Type--Disease prevalence study (cohort design) Level of Evidence 2a. What's known on the subject? and What does the study add? Several studies have estimated the potential association of urinary calculus (UC) with chronic kidney disease (CKD). However, previous literature focusing on this issue tended to evaluate the impact of kidney stones alone on incident CKD, with no studies having been conducted investigating the association between CKD and stone formation in other portions of the urological system. We found that patients with CKD were consistently more likely than comparison subjects to have been previously diagnosed with kidney calculus (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.95-2.27), ureter calculus (OR 1.68, 95% CI 1.51-1.85), bladder calculus (OR 1.49, 95% CI 1.13-1.98), and unspecified calculus (OR 1.89, 95% CI 1.74-2.06). We concluded that there was an association between CKD and UC regardless of stone location. • To explore the association of chronic kidney disease (CKD) with prior kidney calculus, ureter calculus, and bladder calculus using a population-based dataset in Taiwan. Several studies have estimated the potential association of urinary calculus (UC) with CKD. However, previous literature focusing on this issue tended to evaluate the impact of kidney stones alone on incident CKD, with no studies having been conducted investigating the association between CKD and stone formation in other portions of the urological system. • We identified 21,474 patients who received their first-time diagnosis of CKD between 2001 and 2009. • The 21,474 controls were frequency-matched with cases for sex, age group, and index year. • We used conditional logistic regression analyses to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) as an estimation of association between CKD and having been previously diagnosed with UC. • The results show that compared with controls, the OR of prior UC for cases was 1

  1. Association studies using family pools of outcrossing crops based on allele-frequency estimates from DNA sequencing

    DEFF Research Database (Denmark)

    Ashraf, Bilal; Jensen, Just; Asp, Torben

    2014-01-01

    effect from F2-family pools was verified and it was shown that the underestimation of the allele effect is correctly described. The optimal design for an association study when sequencing budget would be fixed is obtained using large sample size and lower sequence depth, and using higher SNP density......F2 families are frequently used in breeding of outcrossing species, for instance to obtain trait measurements on plots. We propose to perform association studies by obtaining a matching “family genotype” from sequencing a pooled sample of the family, and to directly use allele frequencies computed...... (resulting in higher LD with causative mutations) and lower sequencing depth. Therefore, association studies using genotyping by sequencing are optimal and use low sequencing depth per sample. The developed framework for association studies using allele frequencies from sequencing can be modified for other...

  2. Population-specific haplotype association of the postsynaptic density gene DLG4 with schizophrenia, in family-based association studies.

    Directory of Open Access Journals (Sweden)

    Shabeesh Balan

    Full Text Available The post-synaptic density (PSD of glutamatergic synapses harbors a multitude of proteins critical for maintaining synaptic dynamics. Alteration of protein expression levels in this matrix is a marked phenomenon of neuropsychiatric disorders including schizophrenia, where cognitive functions are impaired. To investigate the genetic relationship of genes expressed in the PSD with schizophrenia, a family-based association analysis of genetic variants in PSD genes such as DLG4, DLG1, PICK1 and MDM2, was performed, using Japanese samples (124 pedigrees, n = 376 subjects. Results showed a significant association of the rs17203281 variant from the DLG4 gene, with preferential transmission of the C allele (p = 0.02, although significance disappeared after correction for multiple testing. Replication analysis of this variant, found no association in a Chinese schizophrenia cohort (293 pedigrees, n = 1163 subjects or in a Japanese case-control sample (n = 4182 subjects. The DLG4 expression levels between postmortem brain samples from schizophrenia patients showed no significant changes from controls. Interestingly, a five marker haplotype in DLG4, involving rs2242449, rs17203281, rs390200, rs222853 and rs222837, was enriched in a population specific manner, where the sequences A-C-C-C-A and G-C-C-C-A accumulated in Japanese (p = 0.0009 and Chinese (p = 0.0007 schizophrenia pedigree samples, respectively. However, this could not be replicated in case-control samples. None of the variants in other examined candidate genes showed any significant association in these samples. The current study highlights a putative role for DLG4 in schizophrenia pathogenesis, evidenced by haplotype association, and warrants further dense screening for variants within these haplotypes.

  3. Temperament Is Associated With Outdoor Free Play in Young Children: A TARGet Kids! Study.

    Science.gov (United States)

    Sharp, Julia R; Maguire, Jonathon L; Carsley, Sarah; Abdullah, Kawsari; Chen, Yang; Perrin, Eliana M; Parkin, Patricia C; Birken, Catherine S

    Outdoor free play is important for preschoolers' physical activity, health, and development. Certain temperamental characteristics are associated with obesity, nutrition, and sedentary behaviors in preschoolers, but the relationship between temperament and outdoor play has not been examined. This study examined whether there is an association between temperament and outdoor play in young children. Healthy children aged 1 to 5 years recruited to The Applied Research Group for Kids (TARGet Kids!), a community-based primary care research network, from July 2008 to September 2013 were included. Parent-reported child temperament was assessed using the Childhood Behavior Questionnaire. Outdoor free play and other potential confounding variables were assessed through validated questionnaires. Multivariable linear regression was used to determine the association between temperament and outdoor play, adjusted for potential confounders. There were 3393 children with data on outdoor play. The association between negative affectivity and outdoor play was moderated by sex; in boys, for every 1-point increase in negative affectivity score, mean outdoor play decreased by 4.7 minutes per day. There was no significant association in girls. Surgency was associated with outdoor play; for every 1-point increase in surgency/extraversion, outdoor play increased by 4.6 minutes per day. Young children's temperamental characteristics were associated with their participation in outdoor free play. Consideration of temperament could enhance interventions and strategies to increase outdoor play in young children. Longitudinal studies are needed to elucidate the relationship between children's early temperament and physical activity. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  4. Comparative studies of cyanobacterial associations with crop plants

    NARCIS (Netherlands)

    Ahmed, M.; Stal, L.J.; Hasnain, S.

    2009-01-01

    Cyanobacteria are very sociable organisms having ability to form symbiotic relationships with a variety of organisms from all other domains of life. Their association with plants is of prime importance. Very less work is done on development of new artificial symbiotic associations between

  5. Factors Associated with Remission of Eczema in Children: a Population-based Follow-up Study.

    OpenAIRE

    von Kobyletzki, Laura; Bornehag, Carl-Gustaf; Breeze, Elizabeth; Larsson, Malin; Boman Lindström, Cecilia; Svensson, Åke

    2014-01-01

    The aim of this study was to analyse factors associated with remission of atopic dermatitis (AD) in childhood. A population-based AD cohort of 894 children aged 1-3 years from a cross-sectional baseline study in 2000 was followed up in 2005. The association between remission, background, health, lifestyle, and environmental variables was estimated with crude and multivariable logistic regression. At follow-up, 52% of the children had remission. Independent factors at baseline predicting remis...

  6. Genome-wide association studies identify four ER negative-specific breast cancer risk loci

    DEFF Research Database (Denmark)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara

    2013-01-01

    differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls......), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER...

  7. 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.

  8. A genome-wide association study reveals variants in ARL15 that influence adiponectin levels

    NARCIS (Netherlands)

    J.B. Richards (Brent); D. Waterworth (Dawn); S. O'Rahilly (Stephen); M.-F. Hivert (Marie-France); R.J.F. Loos (Ruth); J.R.B. Perry (John); T. Tanaka (Toshiko); N.J. Timpson (Nicholas); R.K. Semple (Robert); N. Soranzo (Nicole); K. Song (Kijoung); N. Rocha (Nuno); E. Grundberg (Elin); J. Dupuis (Josée); J.C. Florez (Jose); C. Langenberg (Claudia); I. Prokopenko (Inga); R. Saxena (Richa); R. Sladek (Rob); Y.S. Aulchenko (Yurii); D.M. Evans (David); G. Waeber (Gérard); M.S. Burnett; N. Sattar (Naveed); J. Devaney (Joseph); C. Willenborg (Christina); A. Hingorani (Aroon); J.C.M. Witteman (Jacqueline); P. Vollenweider (Peter); B. Glaser (Beate); C. Hengstenberg (Christian); L. Ferrucci (Luigi); D. Melzer (David); K. Stark (Klaus); J. Deanfield (John); J. Winogradow (Janina); M. Grassl (Martina); A.S. Hall (Alistair); J.M. Egan (Josephine); J.R. Thompson (John); S.L. Ricketts (Sally); I.R. König (Inke); W. Reinhard (Wibke); S.M. Grundy (Scott); H.E. Wichmann (Heinz Erich); P. Barter (Phil); R. Mahley (Robert); Y.A. Kesaniemi (Antero); D.J. Rader (Daniel); M.P. Reilly (Muredach); S.E. Epstein (Stephen); A.F.R. Stewart (Alexandre); P. Tikka-Kleemola (Päivi); H. Schunkert (Heribert); K.A. Burling (Keith); J. Erdmann (Jeanette); P. Deloukas (Panagiotis); T. Pastinen (Tomi); N.J. Samani (Nilesh); R. McPherson (Ruth); G.D. Smith; T.M. Frayling (Timothy); N.J. Wareham (Nick); J.B. Meigs (James); V. Mooser (Vincent); T.D. Spector (Timothy)

    2009-01-01

    textabstractThe adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of

  9. Using rice genome-wide association studies to identify DNA markers for marker-assisted selection

    Science.gov (United States)

    Rice association mapping panels are collections of rice (Oryza sativa L.) accessions developed for genome-wide association (GWA) studies. One of these panels, the Rice Diversity Panel 1 (RDP1) was phenotyped by various research groups for several traits of interest, and more recently, genotyped with...

  10. Associative (prosop)agnosia without (apparent) perceptual deficits: a case-study.

    Science.gov (United States)

    Anaki, David; Kaufman, Yakir; Freedman, Morris; Moscovitch, Morris

    2007-04-09

    In associative agnosia early perceptual processing of faces or objects are considered to be intact, while the ability to access stored semantic information about the individual face or object is impaired. Recent claims, however, have asserted that associative agnosia is also characterized by deficits at the perceptual level, which are too subtle to be detected by current neuropsychological tests. Thus, the impaired identification of famous faces or common objects in associative agnosia stems from difficulties in extracting the minute perceptual details required to identify a face or an object. In the present study, we report the case of a patient DBO with a left occipital infarct, who shows impaired object and famous face recognition. Despite his disability, he exhibits a face inversion effect, and is able to select a famous face from among non-famous distractors. In addition, his performance is normal in an immediate and delayed recognition memory for faces, whose external features were deleted. His deficits in face recognition are apparent only when he is required to name a famous face, or select two faces from among a triad of famous figures based on their semantic relationships (a task which does not require access to names). The nature of his deficits in object perception and recognition are similar to his impairments in the face domain. This pattern of behavior supports the notion that apperceptive and associative agnosia reflect distinct and dissociated deficits, which result from damage to different stages of the face and object recognition process.

  11. Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family-based association study

    Science.gov (United States)

    Gonzalez, Suzanne; Xu, Chun; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Contreras, Salvador A; Contreras, Javier; Dassori, Albana; Leach, Robin J; Flores, Deborah; Jerez, Alvaro; Raventós, Henriette; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael

    2013-01-01

    Objectives Through recent genome-wide association studies (GWAS), several groups have reported significant association between variants in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) and bipolar disorder (BP) in European and European-American cohorts. We performed a family-based association study to determine whether CACNA1C is associated with BP in the Latino population. Methods This study consisted of 913 individuals from 215 Latino pedigrees recruited from the United States, Mexico, Guatemala, and Costa Rica. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single-nucleotide polymorphisms (SNPs) that spanned a 602.9 kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family-Based Association Test (version 2.0.3) and Haploview (version 4.2) software. Results An eight-locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15). Conclusions Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population. PMID:23437964

  12. Associations between work stress and suicidal ideation: Individual-participant data from six cross-sectional studies.

    Science.gov (United States)

    Loerbroks, Adrian; Cho, Sung-Il; Dollard, Maureen F; Zou, Jianfang; Fischer, Joachim E; Jiang, Yueying; Angerer, Peter; Herr, Raphael M; Li, Jian

    2016-11-01

    Epidemiological evidence suggests that work stress is associated with suicidal ideation (SI). However, only few studies in this area have drawn on well-established theoretical work stress models (i.e., the job-demand-control [JDC] model, the effort-reward-imbalance [ERI] model, and the model of organizational injustice [OJ]). Utilization of such models allows though for theory-based assessments and workplace interventions. Since evidence on those models' relationship with suicide-related outcomes is currently inconclusive (with regard to JDC), markedly sparse (OJ) or lacking (ERI), we aimed to provide additional or initial evidence. We drew on original data from six cross-sectional studies, which were conducted in four countries (i.e., South Korea, China, Australia, and Germany). Work stress was measured by established questionnaires and was categorized into tertiles. In each study, SI was assessed by either one or two items taken from validated scales. Associations of work stress with SI were estimated for each study and were pooled across studies using multivariate random-effects logistic modeling. In the pooled analyses (n=12,422) all three work stress models were significantly associated with SI with odds ratios fluctuating around 2. For instance, the pooled odds ratios for highest versus lowest work stress exposure in terms of job strain, OJ, and ERI equalled 1.91 (95% confidence interval [CI]=1.52, 2.41), 1.98 (95% CI=1.48, 2.65), and 2.77 (95% CI=1.57, 4.88), respectively. Patterns of associations were largely consistent across the individual studies. Our study provides robust evidence of a positive association between work stress and SI. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. An epigenome-wide association study in whole blood of measures of adiposity among Ghanaians: the RODAM study

    NARCIS (Netherlands)

    Meeks, Karlijn A. C.; Henneman, Peter; Venema, Andrea; Burr, Tom; Galbete, Cecilia; Danquah, Ina; Schulze, Matthias B.; Mockenhaupt, Frank P.; Owusu-Dabo, Ellis; Rotimi, Charles N.; Addo, Juliet; Smeeth, Liam; Bahendeka, Silver; Spranger, Joachim; Mannens, Marcel M. A. M.; Zafarmand, Mohammad H.; Agyemang, Charles; Adeyemo, Adebowale

    2017-01-01

    Background: Epigenome-wide association studies (EWAS) have identified DNA methylation loci involved in adiposity. However, EWAS on adiposity in sub-Saharan Africans are lacking despite the high burden of adiposity among African populations. We undertook an EWAS for anthropometric indices of

  14. Genome Wide Association Study to Identify SNPs and CNPs Associated with Development of Radiation Injury in Prostate Cancer Patients Treated with Radiotherapy

    Science.gov (United States)

    2012-10-01

    association tests, we obtained low genomic inflation factors of 1.02 for the ED patients and 1.00 for the urinary morbidity patients, suggesting...study (GWAS) to identify genetic factors associated with urinary morbidity following radiotherapy for prostate cancer. Methods: Prostate cancer...increased urinary frequency, incomplete bladder emptying, weak urinary stream and incontinence , as well as more serious events such as bladder necrosis or

  15. Genome-wide Association Study Identifies New Loci for Resistance to Leptosphaeria maculans in Canola

    Directory of Open Access Journals (Sweden)

    Harsh Raman

    2016-10-01

    Full Text Available Blackleg, caused by Leptosphaeria maculans, is a significant disease which affects the sustainable production of canola. This study reports a genome-wide association study based on 18,804 polymorphic SNPs to identify loci associated with qualitative and quantitative resistance to L. maculans. Genomic regions delimited with 503 significant SNP markers, that are associated with resistance evaluated using 12 single spore isolates and pathotypes from four canola stubble were identified. Several significant associations were detected at known disease resistance loci including in the vicinity of recently cloned Rlm2/LepR3 genes, and at new loci on chromosomes A01/C01, A02/C02, A03/C03, A05/C05, A06, A08, and A09. In addition, we validated statistically significant associations on A01, A07 and A10 in four genetic mapping populations, demonstrating that GWAS marker loci are indeed associated with resistance to L. maculans. One of the novel loci identified for the first time, Rlm12, conveys adult plant resistance and mapped within 13.2 kb from Arabidopsis R gene of TIR-NBS class. We showed that resistance loci are located in the vicinity of R genes of A. thaliana and B. napus on the sequenced genome of B. napus cv. Darmor-bzh. Significantly associated SNP markers provide a valuable tool to enrich germplasm for favorable alleles in order to improve the level of resistance to L. maculans in canola.

  16. Impaired Fertility Associated with Subclinical Hypothyroidism and Thyroid Autoimmunity: The Danish General Suburban Population Study

    Directory of Open Access Journals (Sweden)

    Anne-Dorthe Feldthusen

    2015-01-01

    Full Text Available Introduction. The aim of this study was to estimate the significance of TSH, thyroid peroxidase antibody (TPOAb, and mild (subclinical hypothyroidism in women from The Danish General Suburban Population Study (GESUS on the number of children born, the number of pregnancies, and the number of spontaneous abortions. Methods. Retrospective cross sectional study of 11254 women participating in GESUS. Data included biochemical measurements and a self-administrated questionnaire. Results. 6.7% had mild (subclinical hypothyroidism and 9.4% prevalent hypothyroidism. In women with mild hypothyroidism TPOAb was significantly elevated and age at first child was older compared to controls. TSH and TPOAb were negatively linearly associated with the number of children born and the number of pregnancies in the full cohort in age-adjusted and multiadjusted models. TSH or TPOAb was not associated with spontaneous abortions. Mild (subclinical hypothyroidism was associated with a risk of not having children and a risk of not getting pregnant in age-adjusted and multiadjusted models. Prevalent hypothyroidism was not associated with the number of children born, the number of pregnancies, or spontaneous abortions. Conclusion. Impaired fertility is associated with TSH, TPOAb, and mild (subclinical hypothyroidism in a Danish population of women.

  17. Long sleep duration is associated with lower cognitive function among middle-age adults - the Doetinchem Cohort Study.

    Science.gov (United States)

    van Oostrom, Sandra H; Nooyens, Astrid C J; van Boxtel, Martin P J; Verschuren, W M Monique

    2018-01-01

    In older adults, both short and long sleep duration are associated with lower cognitive function, suggesting an inverted U-shaped association between sleep duration and cognitive outcomes. This study examined whether sleep duration is associated with (changes in) cognitive function in a middle-aged population. In the Doetinchem Cohort Study, the cognitive function of 2970 men and women aged 41-75 years at baseline (1995-2007) was examined 2-3 times, with 5-year time intervals. Global cognitive function and the domains memory, information processing speed, and cognitive flexibility were assessed. In multivariable linear regression models, (change in) self-reported sleep duration was studied in association with the level and change in cognitive function. In a subsample of the population (n = 2587), the association of sleep duration and feeling rested with cognitive function was studied. Sleep duration of 9 h and more was statistically significantly associated with lower global cognitive function (p cognitive function. An inverted U-shaped association between sleep duration and cognitive function was observed for speed, flexibility, and global cognitive function. Sleep duration was not associated with change in cognitive function. Middle-age adults with long sleep duration had a lower cognitive function. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. The association between foodborne and orofecal pathogens and allergic sensitisation -- EuroPrevall study

    NARCIS (Netherlands)

    Janse, Jacqueline J.; Wong, Gary W. K.; Potts, James; Ogorodova, Ludmila M.; Fedorova, Olga S.; Mahesh, P. A.; Sakellariou, Alexandros; Papadopoulos, Nikolaos G.; Knulst, André C.; Versteeg, Serge A.; Kroes, Aloys C. M.; Vossen, Ann C. T. M.; Campos Ponce, Maiza; Kummeling, Ischa; Burney, Peter; van Ree, Ronald; Yazdanbakhsh, Maria

    2014-01-01

    An inverse association between markers of exposure to foodborne and orofecal pathogens and allergic sensitization has been reported. However, the findings of epidemiological studies have not been consistent. This study investigated the relationship between antibodies to hepatitis A, Toxoplasma

  19. The association between foodborne and orofecal pathogens and allergic sensitisation - EuroPrevall study

    NARCIS (Netherlands)

    Janse, J.J.; Wong, G.W.K.; Potts, J.; Ogorodova, L.M.; Fedorova, O.S.; Mahesh, P.A.; Sakellariou, A.; Papadopoulos, N.G.; Knulst, A.C.; Versteeg, S.A.; Kroes, A.C.M.; Vossen, A.C.T.M.; Campos Ponce, M.; Kummeling, I.; Burney, P.; van Ree, R.; Yazdanbakhsh, M.

    2014-01-01

    Background: An inverse association between markers of exposure to foodborne and orofecal pathogens and allergic sensitization has been reported. However, the findings of epidemiological studies have not been consistent. This study investigated the relationship between antibodies to hepatitis A,

  20. Oral soft tissue disorders are associated with gastroesophageal reflux disease: retrospective study.

    Science.gov (United States)

    Watanabe, Masaaki; Nakatani, Eiji; Yoshikawa, Hiroo; Kanno, Takahiro; Nariai, Yoshiki; Yoshino, Aya; Vieth, Michael; Kinoshita, Yoshikazu; Sekine, Joji

    2017-08-07

    Dental erosion (DE), one of oral hard tissue diseases, is one of the extraoesophageal symptoms defined as the Montreal Definition and Classification of gastroesophageal reflux disease (GERD). However, no study evaluated the relationship between GERD and oral soft tissues. We hypothesized that oral soft tissue disorders (OSTDs) would be related to GERD. The study aimed to investigate the association OSTDs and GERD. GERD patients (105 cases), older and younger controls (25 cases each) were retrospectively examined for oral symptoms, salivary flow volume (Saxon test), swallowing function (repetitive saliva swallowing test [RSST]), teeth (decayed, missing, and filled [DMF] indices), and soft tissues (as evaluation of OSTDs, gingivitis; papillary, marginal, and attached [PMA] gingival indexes, simplified oral hygiene indices [OHI-S], and inflammatory oral mucosal regions). Clinical histories, which included body mass index [BMI], the existence of alcohol and tobacco use, and bruxism, were also investigated. A P value of bruxism, as an exacerbation factor of periodontal disease, in the GERD patients was significantly more frequent than in either control group (P = 0.041). OSTDs were associated with GERD, which was similar to the association between DE and GERD.

  1. The Generalized Higher Criticism for Testing SNP-Set Effects in Genetic Association Studies

    Science.gov (United States)

    Barnett, Ian; Mukherjee, Rajarshi; Lin, Xihong

    2017-01-01

    It is of substantial interest to study the effects of genes, genetic pathways, and networks on the risk of complex diseases. These genetic constructs each contain multiple SNPs, which are often correlated and function jointly, and might be large in number. However, only a sparse subset of SNPs in a genetic construct is generally associated with the disease of interest. In this article, we propose the generalized higher criticism (GHC) to test for the association between an SNP set and a disease outcome. The higher criticism is a test traditionally used in high-dimensional signal detection settings when marginal test statistics are independent and the number of parameters is very large. However, these assumptions do not always hold in genetic association studies, due to linkage disequilibrium among SNPs and the finite number of SNPs in an SNP set in each genetic construct. The proposed GHC overcomes the limitations of the higher criticism by allowing for arbitrary correlation structures among the SNPs in an SNP-set, while performing accurate analytic p-value calculations for any finite number of SNPs in the SNP-set. We obtain the detection boundary of the GHC test. We compared empirically using simulations the power of the GHC method with existing SNP-set tests over a range of genetic regions with varied correlation structures and signal sparsity. We apply the proposed methods to analyze the CGEM breast cancer genome-wide association study. Supplementary materials for this article are available online. PMID:28736464

  2. Irreversible colloidal agglomeration in presence of associative inhibitors: Computer simulation study

    International Nuclear Information System (INIS)

    Barcenas, Mariana; Duda, Yurko

    2007-01-01

    Monte Carlo simulation is employed to study the irreversible particle-cluster agglomeration of valence-limited colloids affected by associative inhibitors. The cluster size distribution and number of connections between colloids are analyzed as a function of density and inhibitor concentration. The influence of colloid functionality on its aggregation is discussed

  3. Factors associated with occupational strain among Chinese teachers: a cross-sectional study.

    Science.gov (United States)

    Yang, X; Wang, L; Ge, C; Hu, B; Chi, T

    2011-02-01

    With the reform of the education system in China, teachers are suffering from more occupational strain, which is believed to impair their working state indirectly and affect their health. This study assessed occupational strain and explored the related factors among Chinese teachers. Cross-sectional with cluster sampling. The study population was composed of 3570 school teachers working in 64 primary and middle schools in Heping District in Shenyang, China. Data were collected using a self-administered questionnaire (the Chinese version of the Occupational Stress Inventory scale). Multivariate linear regression analyses were performed to study the factors related to occupational strain. The average score on the Personal Strain Questionnaire (PSQ) for the whole study population was 106.5 (107.5 in men and 106.3 in women). Teachers with chronic disease, a greater number of days of sick leave, recent experience of a stressful life event and divorced/separated/widowed status tended to suffer greater strain than their peers. Regression analyses showed that the PSQ score was significantly associated with role overload, role boundary, responsibility and physical environment, and inversely associated with recreation and rational coping. The most crucial predictors of occupational strain were chronic disease, days of sick leave, recent experience of a stressful life event and marital status. Being a class teacher was the strongest indicator of interpersonal strain. Self-care was associated with vocational strain and psychological strain, and inversely associated with physical strain. Most teachers in this study experienced a high degree of occupational strain. Chronic disease, days of sick leave, recent experience of a stressful life event and divorced/separated/widowed status played prominent roles in occupational strain. In addition, role overload, role boundary, responsibility and physical environment induce occupational strain, while recreation and rational coping have

  4. Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study

    Science.gov (United States)

    OBJECTIVES: The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND: Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying c...

  5. Factors associated with pharmacy student interest in international study.

    Science.gov (United States)

    Owen, Chelsea; Breheny, Patrick; Ingram, Richard; Pfeifle, William; Cain, Jeff; Ryan, Melody

    2013-04-12

    OBJECTIVES. To examine the interest of pharmacy students in international study, the demographic factors and involvement characteristics associated with that interest, and the perceived advantages and barriers of engaging in international opportunities during pharmacy school. METHODS. A self-administered electronic survey instrument was distributed to first-, second-, and third-year pharmacy students at the University of Kentucky College of Pharmacy. RESULTS. There were 192 total respondents, for a response rate of 50.9%. Seventy-two percent reported interest in international study. Previous international study experience (p=0.001), previous international travel experience (p=0.002), year in pharmacy school (p=0.03), level of academic involvement (pinternational study interest. Positive influences to international study included desire to travel and availability of scholarships. Perceived barriers included an inability to pay expenses and lack of foreign language knowledge. CONCLUSIONS. The needs and interests of pharmacy students should be considered in the development and expansion of internationalization programs in order to effectively optimize global partnerships and available international experiences. Colleges and schools of pharmacy should engage students early in the curriculum when interest in study-abroad opportunities is highest and seek to alleviate concerns about expenses as a primary influence on study-abroad decisions through provision of financial assistance.

  6. 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.

  7. Factors of U.S. Hospitals Associated with Improved Profit Margins: An Observational Study.

    Science.gov (United States)

    Ly, Dan P; Cutler, David M

    2018-02-14

    Hospitals face financial pressure from decreased margins from Medicare and Medicaid and lower reimbursement from consolidating insurers. The objectives of this study are to determine whether hospitals that became more profitable increased revenues or decreased costs more and to examine characteristics associated with improved financial performance over time. The design of this study is retrospective analyses of U.S. non-federal acute care hospitals between 2003 and 2013. There are 2824 hospitals as subjects of this study. The main measures of this study are the change in clinical operating margin, change in revenues per bed, and change in expenses per bed between 2003 and 2013. Hospitals that became more profitable had a larger magnitude of increases in revenue per bed (about $113,000 per year [95% confidence interval: $93,132 to $133,401]) than of decreases in costs per bed (about - $10,000 per year [95% confidence interval: - $28,956 to $9617]), largely driven by higher non-Medicare reimbursement. Hospitals that improved their margins were larger or joined a hospital system. Not-for-profit status was associated with increases in operating margin, while rural status and having a larger share of Medicare patients were associated with decreases in operating margin. There was no association between improved hospital profitability and changes in diagnosis related group weight, in number of profitable services, or in payer mix. Hospitals that became more profitable were more likely to increase their admissions per bed per year. Differential price increases have led to improved margins for some hospitals over time. Where significant price increases are not possible, hospitals will have to become more efficient to maintain profitability.

  8. The association of nursing students' mobile phone dependence with their health behaviors: a pilot study

    OpenAIRE

    Maria Avramika; Maria Gkrizioti; Athanasios Mastrokostas; Thalia Bellali; Kyriaki Tileniki

    2012-01-01

    Mobile phone use is such a common phenomenon nowadays, that many researchers refer to children and adolescents as a 'mobile generation'. Several studies associate mobile phone use (in terms of voice communication, text sending and internet use with psychological, social and physiological outcomes. Aim: The aim of this study was the exploration of the association of mobile phone dependence with health behaviors in a population οf students of nursing. Material-Method: This study, which follows ...

  9. Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-04-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

  10. Genome-wide association studies dissect the genetic networks underlying agronomical traits in soybean.

    Science.gov (United States)

    Fang, Chao; Ma, Yanming; Wu, Shiwen; Liu, Zhi; Wang, Zheng; Yang, Rui; Hu, Guanghui; Zhou, Zhengkui; Yu, Hong; Zhang, Min; Pan, Yi; Zhou, Guoan; Ren, Haixiang; Du, Weiguang; Yan, Hongrui; Wang, Yanping; Han, Dezhi; Shen, Yanting; Liu, Shulin; Liu, Tengfei; Zhang, Jixiang; Qin, Hao; Yuan, Jia; Yuan, Xiaohui; Kong, Fanjiang; Liu, Baohui; Li, Jiayang; Zhang, Zhiwu; Wang, Guodong; Zhu, Baoge; Tian, Zhixi

    2017-08-24

    Soybean (Glycine max [L.] Merr.) is one of the most important oil and protein crops. Ever-increasing soybean consumption necessitates the improvement of varieties for more efficient production. However, both correlations among different traits and genetic interactions among genes that affect a single trait pose a challenge to soybean breeding. To understand the genetic networks underlying phenotypic correlations, we collected 809 soybean accessions worldwide and phenotyped them for two years at three locations for 84 agronomic traits. Genome-wide association studies identified 245 significant genetic loci, among which 95 genetically interacted with other loci. We determined that 14 oil synthesis-related genes are responsible for fatty acid accumulation in soybean and function in line with an additive model. Network analyses demonstrated that 51 traits could be linked through the linkage disequilibrium of 115 associated loci and these links reflect phenotypic correlations. We revealed that 23 loci, including the known Dt1, E2, E1, Ln, Dt2, Fan, and Fap loci, as well as 16 undefined associated loci, have pleiotropic effects on different traits. This study provides insights into the genetic correlation among complex traits and will facilitate future soybean functional studies and breeding through molecular design.

  11. 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.

  12. Association Study between Ghrelin Gene Polymorphism and Metabolic Syndrome in a Han Chinese Population.

    Science.gov (United States)

    You, Yueyue; Yu, Yaqin; Wu, Yanhua; Rao, Wenwang; Zhang, Yangyu; Liu, Yingyu; Yang, Guang; Fu, Yingli; Shi, Jieping; Kou, Changgui

    2017-01-01

    Ghrelin, in humans, is a hormone secreted from the stomach with an orexigenic effect, which is good for digestion and absorption, as well as regulating physical growth, metabolism, and energy balance. It is also involved in the development of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). This study assessed the association between single nucleotide variants of the GHRL gene and the risk of metabolic syndrome in a Han Chinese population. A case-control study was performed on 3780 Han Chinese comprising 1813 MetS cases and 1967 controls. Three missense polymorphisms in GHRL (rs26802, rs10490816, and rs696217) were selected, and the association between these polymorphisms and the risk of MetS was investigated. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation (IDF). Using Pearson's 2 test, we found that there were no significant differences in genotype distributions and allele frequencies between cases and controls (all p > 0.05). There were also no significant differences in haplotype distributions between MetS cases and healthy controls. Furthermore, we confirmed that rs26802 of the GHRL gene is associated with body mass index (BMI), waist circumference, systolic blood pressure (SBP), and fasting glucose; rs10490816 is associated with triglycerides (TG) and total cholesterol (TC); while rs696217 is associated with hip circumference and fasting glucose. We concluded that mutations in the GHRL gene did not confer risk for MetS in our study population. Therefore, functional analysis and replication studies in other populations are needed to further investigate the exact role of the GHRL gene in MetS.

  13. A generalized Kruskal-Wallis test incorporating group uncertainty with application to genetic association studies.

    Science.gov (United States)

    Acar, Elif F; Sun, Lei

    2013-06-01

    Motivated by genetic association studies of SNPs with genotype uncertainty, we propose a generalization of the Kruskal-Wallis test that incorporates group uncertainty when comparing k samples. The extended test statistic is based on probability-weighted rank-sums and follows an asymptotic chi-square distribution with k - 1 degrees of freedom under the null hypothesis. Simulation studies confirm the validity and robustness of the proposed test in finite samples. Application to a genome-wide association study of type 1 diabetic complications further demonstrates the utilities of this generalized Kruskal-Wallis test for studies with group uncertainty. The method has been implemented as an open-resource R program, GKW. © 2013, The International Biometric Society.

  14. Joint associations of insomnia and sleep duration with prevalent diabetes: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

    Science.gov (United States)

    Cespedes, Elizabeth M; Dudley, Katherine A; Sotres-Alvarez, Daniela; Zee, Phyllis C; Daviglus, Martha L; Shah, Neomi A; Talavera, Gregory A; Gallo, Linda C; Mattei, Josiemer; Qi, Qibin; Ramos, Alberto R; Schneiderman, Neil; Espinoza-Giacinto, Rebeca A; Patel, Sanjay R

    2016-05-01

    Inadequate sleep quantity and quality are associated with a higher risk of type 2 diabetes. This relationship is not well-examined in U.S. Hispanics/Latinos, and prior analyses may be confounded by sleep apnea. This cross-sectional study examined joint associations of sleep duration and insomnia with diabetes among diverse U.S. Hispanic/Latinos. Baseline data on sleep quantity and quality were obtained from 15,227 participants (mean age 41; range 18-74 years) from the Hispanic Community Health Study/Study of Latinos. Complex survey multinomial logistic regression was used to examine associations between prevalent diabetes and six phenotypes defined by cross-classifying sleep duration (short ≤6 h, average >6-9 h, long >9 h) and insomnia, adjusting for sex, age, site and Hispanic/Latino background interaction, education, physical activity, diet quality, and sleep apnea. In the weighted population, 14% had diabetes, 28% had insomnia, 9% were short sleepers, and 19% were long sleepers. Compared with those with average sleep and no insomnia, those with short sleep and insomnia were more likely to have diabetes (odds ratio [OR] 1.46; 95% confidence interval [CI] 1.02, 2.11). Average sleepers with insomnia (1.28; 95% CI 1.02, 1.61) and long sleepers without insomnia (1.33; 95% CI 1.07, 1.65) also had elevated odds of diabetes. Further adjustment for body mass index attenuated associations, except with long sleep without insomnia. Both decreased quantity and quality of sleep are associated with diabetes in Hispanic/Latinos, with the greatest odds among those with short sleep duration and insomnia. The association is largely explained by obesity. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  15. Patient characteristics associated with measurement of routine diabetes care: an observational study.

    Directory of Open Access Journals (Sweden)

    Arna L Van Doorn-Klomberg

    Full Text Available Non-modifiable patient characteristics, including age, gender, ethnicity as well as the occurrence of multi-morbidities, are associated with processes and outcomes of diabetes care. Information on these factors can be used in case mix adjustment of performance measures. However, the practical relevance of such adjustment is not clear. The aim of this study was to assess the strength of associations between patient factors and diabetes care processes and outcomes.We performed an observational study based on routinely collected data of 12,498 diabetes patients in 59 Dutch primary care practices. Data were collected on patient age, gender, whether the patient lived in a deprived area, body mass index and the co-occurrence of cardiovascular disease, chronic obstructive pulmonary disease, depression or anxiety. Outcomes included 6 dichotomous measures (3 process and 3 outcome related regarding glycosylated hemoglobin, systolic blood pressure and low density lipoprotein-cholesterol. We performed separate hierarchical logistic mixed model regression models for each of the outcome measures.Each of the process measure models showed moderate effect sizes, with pooled areas under the curve that varied between 0.66 and 0.76. The frequency of diabetes related consultations as a measure of patient compliance to treatment showed the strongest association with all process measures (odds ratios between 5.6 and 14.5. The effect sizes of the outcome measure models were considerably smaller than the process measure models, with pooled areas under the curve varying from 0.57 to 0.61.Several non-modifiable patient factors could be associated with processes and outcomes of diabetes care. However, associations were small. These results suggest that case-mix correction or stratification in assessing diabetes care has limited practical relevance.

  16. 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

  17. Genetic association studies of suicidal behaviour: A review of the past 10 years, progress, limitations and future directions.

    Directory of Open Access Journals (Sweden)

    BOJAN MIRKOVIC

    2016-09-01

    Full Text Available Suicidal behaviours, which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in suicidal behaviour is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in suicidal behaviours including (i case-control studies, (ii family-based association studies and (iii genome-wide association studies (GWAS. Various studies on genetic associations have tended to suggest that a number of genes (e.g., tryptophan hydroxylase, serotonin receptors and transporters or brain-derived neurotrophic factors are linked to suicidal behaviours, but these findings are not consistently supported by the results obtained. Although the candidate-gene approach is useful, it is hampered by the present state of knowledge concerning the pathophysiology of diseases. Interpretations of GWAS results are mostly hindered by a lack of annotation describing the functions of most variation throughout the genome.Association studies have addressed a wide range of SNPs in numerous genes. We have included 104 such studies, of which 10 are family-based association studies and 11 are GWAS studies. Numerous meta-analyses of case-control studies have shown significant associations of suicidal behaviour with variants in the serotonin transporter gene (5-HTT or SLC6A4 and the tryptophane hydroxylase1 gene (TPH1, but others report contradictory results. The gene encoding brain-derived neurotrophic factor (BDNF and its receptor (NTRK2 are also promising candidates. Only two of the GWAS studies showed any significant associations. Several pathways are mentioned in an attempt to understand the lack of reproducibility and the disappointing results. Consequently, we review and discuss here the following aspects: (i sample characteristics and confounding factors; (ii statistical limits; (iii gene-gene interactions; (iv gene

  18. The relationship between insomnia with short sleep duration is associated with hypercholesterolemia: a cross-sectional study.

    Science.gov (United States)

    Lin, Chia-Ling; Tsai, Yu-Hsia; Yeh, Mei Chang

    2016-02-01

    To examine the association between insomnia with short sleep duration and hypercholesterolemia in Taiwanese adults. Previous studies mostly focused on the association between sleep duration and hyperlipidemia, but the results were not consistent. Besides, very few studies extensively examined the association between insomnia and hypercholesterolemia. This study hypothesized that insomnia with short sleep duration is associated with hypercholesterolemia. Secondary data analysis. This study analysed the latest database of the cross-sectional Nutrition and Health Survey in Taiwan which was released on 2011 (data collected between 2005-2008) and collected data using stratified three-staged probability sampling design. This study analysed 1533 participants aged between 19-64 (733 males and 800 females) and used logistic regression model to calculate the odds ratio and the 95% confidence interval of insomnia with short sleep duration to hypercholesterolemia. Controlled confounders included age, gender, sample weight, body mass index, waist circumference, fasting plasma glucose, hypertension and diabetes. Insomnia with 5-6 hours of sleep duration was significantly associated with hypercholesterolemia. The odds ratio of mild insomnia or moderate/severe insomnia with 5-6 hours of sleep duration to hypercholesterolemia was higher, compared with the reference group (without insomnia and >6 hours of sleep duration). Insomnia with short sleep duration was associated with increased odds of hypercholesterolemia. Caregivers in clinical practice should watch out for the effect brought by this novel factor. © 2015 John Wiley & Sons Ltd.

  19. Genomewide Association Scan of a Mortality Associated Endophenotype for a Long and Healthy Life in the Long Life Family Study

    DEFF Research Database (Denmark)

    Singh, Jatinder; Minster, Ryan L; Schupf, Nicole

    2017-01-01

    Background: Identification of genes or fundamental biological pathways that regulate aging phenotypes and longevity could lead to possible interventions to increase healthy longevity. Methods: Using data from the Long Life Family Study, we performed genomewide association analyses on an endopheno...

  20. 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.

  1. 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.

  2. Frequencies and Associations of Narcolepsy-Related Symptoms: A Cross-Sectional Study.

    Science.gov (United States)

    Kim, Lenise Jihe; Coelho, Fernando Morgadinho; Hirotsu, Camila; Araujo, Paula; Bittencourt, Lia; Tufik, Sergio; Andersen, Monica Levy

    2015-12-15

    Narcolepsy is a disabling disease with a delayed diagnosis. At least 3 years before the disorder identification, several comorbidities can be observed in patients with narcolepsy. The early recognition of narcolepsy symptoms may improve long-term prognosis of the patients. Thus, we aimed to investigate the prevalence of the symptoms associated with narcolepsy and its social and psychological association in a sample of Sao Paulo city inhabitants. We performed a cross-sectional evaluation with 1,008 individuals from the Sao Paulo Epidemiologic Sleep Study (EPISONO). Excessive daytime sleepiness (EDS) was assessed by the Epworth Sleepiness Scale. Volunteers were also asked about the occurrence of cataplectic-like, hypnagogic or hypnopompic hallucinations, and sleep paralysis symptoms. The participants underwent a full-night polysomnography and completed questionnaires about psychological, demographic, and quality of life parameters. We observed a prevalence of 39.2% of EDS, 15.0% of cataplectic-like symptom, 9.2% of hypnagogic or hypnopompic hallucinations, and 14.9% of sleep paralysis in Sao Paulo city inhabitants. A frequency of 6.9% was observed when EDS and cataplectic-like symptoms were grouped. The other associations were EDS + hallucinations (4.7%) and EDS + sleep paralysis (7.5%). Symptomatic participants were predominantly women and younger compared with patients without any narcolepsy symptom (n = 451). Narcolepsy symptomatology was also associated with a poor quality of life and symptoms of depression, anxiety, and fatigue. Narcolepsy-related symptoms are associated with poor quality of life and worse psychological parameters. © 2015 American Academy of Sleep Medicine.

  3. Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.

    LENUS (Irish Health Repository)

    Chen, Jingchun

    2011-09-01

    We conducted data-mining analyses of genome wide association (GWA) studies of the CATIE and MGS-GAIN datasets, and found 13 markers in the two physically linked genes, PTPN21 and EML5, showing nominally significant association with schizophrenia. Linkage disequilibrium (LD) analysis indicated that all 7 markers from PTPN21 shared high LD (r(2)>0.8), including rs2274736 and rs2401751, the two non-synonymous markers with the most significant association signals (rs2401751, P=1.10 × 10(-3) and rs2274736, P=1.21 × 10(-3)). In a meta-analysis of all 13 replication datasets with a total of 13,940 subjects, we found that the two non-synonymous markers are significantly associated with schizophrenia (rs2274736, OR=0.92, 95% CI: 0.86-0.97, P=5.45 × 10(-3) and rs2401751, OR=0.92, 95% CI: 0.86-0.97, P=5.29 × 10(-3)). One SNP (rs7147796) in EML5 is also significantly associated with the disease (OR=1.08, 95% CI: 1.02-1.14, P=6.43 × 10(-3)). These 3 markers remain significant after Bonferroni correction. Furthermore, haplotype conditioned analyses indicated that the association signals observed between rs2274736\\/rs2401751 and rs7147796 are statistically independent. Given the results that 2 non-synonymous markers in PTPN21 are associated with schizophrenia, further investigation of this locus is warranted.

  4. Association of Periodontitis and Subsequent Depression: A Nationwide Population-Based Study.

    Science.gov (United States)

    Hsu, Chih-Chao; Hsu, Yi-Chao; Chen, Hsuan-Ju; Lin, Che-Chen; Chang, Kuang-Hsi; Lee, Chang-Yin; Chong, Lee-Won; Kao, Chia-Hung

    2015-12-01

    Periodontitis is a systemic and chronic inflammatory disease associated with multiple physical conditions. Distress and depression are other problems affecting the progression of periodontitis. However, the causal relationship between depression and periodontitis has not been adequately investigated. This aim of this study was to determine the association between periodontitis and the subsequent development of depression.We identified 12,708 patients with newly diagnosed periodontitis from 2000 to 2005 and 50,832 frequency-matched individuals without periodontitis. Both groups were followed until diagnosed with depression, withdrawal from the National Health Insurance program, or the end of 2011. The association between periodontitis and depressio was analyzed using Cox proportional hazard regression models.The incidence density rate of depression was higher in the periodontitis group than in the nonperiodontitis group, with an adjusted hazard ratio of 1.73 (95% confidence interval 1.58-1.89) when adjusting for sex, age, and comorbidity. Cox models revealed that periodontitis was an independent risk factor for depression in patients, except for comorbidities of diabetes mellitus (DM), alcohol abuse, and cancer.Periodontitis may increase the risk of subsequent depression and was suggested an independent risk factor regardless of sex, age, and most comorbidities. However, DM, alcohol abuse, and cancer may prevent the development of subsequent depression because of DM treatment, the paradoxical effect of alcohol, and emotional distress to cancer, respectively. Prospective studies on the relationship between periodontitis and depression are warranted.

  5. Association between cancer and contact allergy: a linkage study

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Thyssen, Jacob P; Menné, Torkil

    2011-01-01

    by logistic regression analysis. Results An inverse association between contact allergy and non-melanoma skin- and breast cancer, respectively, was identified in both sexes, and an inverse trend for brain cancer was found in women with contact allergy. Additionally, a positive association between contact...... and cancer, few have looked into the association between cancer and contact allergy, a type IV allergy. By linking two clinical databases, the authors investigate the possible association between contact allergy and cancer. Methods Record linkage of two different registers was performed: (1) a tertiary...

  6. Association between cancer and contact allergy: a linkage study

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Thyssen, Jacob P; Menné, Torkil

    2011-01-01

    by logistic regression analysis. Results An inverse association between contact allergy and non-melanoma skin- and breast cancer, respectively, was identified in both sexes, and an inverse trend for brain cancer was found in women with contact allergy. Additionally, a positive association between contact...... allergy and bladder cancer was found. Conclusion The inverse associations support the immunosurveillance hypothesis (ie, individuals with an allergy are less likely to get cancer due to a triggered immune system), while the positive association with bladder cancer could be due to accumulations of chemical...

  7. Relevance Epistasis Network of Gastritis for Intra-chromosomes in the Korea Associated Resource (KARE Cohort Study

    Directory of Open Access Journals (Sweden)

    Hyun-hwan Jeong

    2014-12-01

    Full Text Available Gastritis is a common but a serious disease with a potential risk of developing carcinoma. Helicobacter pylori infection is reported as the most common cause of gastritis, but other genetic and genomic factors exist, especially single-nucleotide polymorphisms (SNPs. Association studies between SNPs and gastritis disease are important, but results on epistatic interactions from multiple SNPs are rarely found in previous genome-wide association (GWA studies. In this study, we performed computational GWA case-control studies for gastritis in Korea Associated Resource (KARE data. By transforming the resulting SNP epistasis network into a gene-gene epistasis network, we also identified potential gene-gene interaction factors that affect the susceptibility to gastritis.

  8. Associations between the peer support relationship, service satisfaction and recovery-oriented outcomes: a correlational study.

    Science.gov (United States)

    Thomas, Elizabeth C; Salzer, Mark S

    2017-12-18

    The working alliance between non-peer providers and mental health consumers is associated with positive outcomes. It is hypothesized that this factor, in addition to other active support elements, is also positively related to peer support service outcomes. This study evaluates correlates of the peer-to-peer relationship and its unique association with service satisfaction and recovery-oriented outcomes. Participants were 46 adults with serious mental illnesses taking part in a peer-brokered self-directed care intervention. Pearson correlation analyses examined associations among peer relationship factors, services-related variables and recovery-oriented outcomes (i.e. empowerment, recovery and quality of life). Hierarchical multiple regression analyses evaluated associations between relationship factors and outcomes over time, controlling for other possible intervention effects. The peer relationship was not related to number of contacts. There were robust associations between the peer relationship and service satisfaction and some recovery-oriented outcomes at 24-months, but not at 12-months. These associations were not explained by other possible intervention effects. This study contributes to a better understanding of the positive, unique association between the peer-to-peer relationship and outcomes, similar to what is found in non-peer-delivered interventions. Implications for program administrators and policymakers seeking to integrate peer specialists into mental health service systems are discussed.

  9. Genome-wide association study of 25(OH) Vitamin D concentrations in Punjabi Sikhs: Results of the Asian Indian diabetic heart study.

    Science.gov (United States)

    Sapkota, Bishwa R; Hopkins, Ruth; Bjonnes, Andrew; Ralhan, Sarju; Wander, Gurpreet S; Mehra, Narinder K; Singh, Jai Rup; Blackett, Piers R; Saxena, Richa; Sanghera, Dharambir K

    2016-04-01

    Vitamin D deficiency is implicated in multiple disease conditions and accumulating evidence supports that the variation in serum vitamin D (25(OH)D) levels, including deficiency, is under strong genetic control. However, the underlying genetic mechanism associated with vitamin 25(OH)D concentrations is poorly understood. We earlier reported a very high prevalence of vitamin D deficiency associated with an increased risk for type 2 diabetes and obesity in a Punjabi Sikh diabetic cohort as part of the Asian Indian diabetic heart study (AIDHS). Here we have performed the first genome-wide association study (GWAS) of serum 25(OH)D on 3538 individuals from this Punjabi Sikh population. Our discovery GWAS comprised of 1387 subjects followed by validation of 24 putative SNPs (P<10(-4)) using an independent replication sample (n=2151) from the same population by direct genotyping. A novel locus at chromosome 20p11.21 represented by rs2207173 with minor allele frequency (MAF) 0.29, [β=-0.13, p=4.47×10(-9)] between FOXA2 and SSTR4 was identified to be associated with 25(OH)D levels. Another suggestive association signal at rs11586313 (MAF 0.54) [β=0.90; p=1.36×10(-6)] was found within the regulatory region of the IVL gene on chromosome 1q21.3. Additionally, our study replicated 3 of 5 known GWAS genes associated with 25(OH)D concentrations including GC (p=0.007) and CYP2R1 (p=0.019) reported in Europeans and the DAB1 (p=0.003), reported in Hispanics. Identification of novel association signals in biologically plausible regions with 25(OH)D metabolism will provide new molecular insights on genetic drivers of vitamin D status and its implications in health disparities. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. A genome-wide association study identifies protein quantitative trait loci (pQTLs.

    Directory of Open Access Journals (Sweden)

    David Melzer

    2008-05-01

    Full Text Available There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8x10(-57, CCL4L1 (p = 3.9x10(-21, IL18 (p = 6.8x10(-13, LPA (p = 4.4x10(-10, GGT1 (p = 1.5x10(-7, SHBG (p = 3.1x10(-7, CRP (p = 6.4x10(-6 and IL1RN (p = 7.3x10(-6 genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R, altered secretion rates of different sized proteins (LPA, variation in gene copy number (CCL4L1 and altered transcription (GGT1. We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha levels (p = 6.8x10(-40, but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis

  11. A Phase II dose titration study of thalidomide for cancer-associated anorexia.

    Science.gov (United States)

    Davis, Mellar; Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Bicanovsky, Leslie; Lagman, Ruth

    2012-01-01

    Sixty-five percent of people with advanced cancer suffers from loss of appetite. Several inflammatory cytokines appear to cause appetite loss in animal models. Thalidomide is an immunomodulatory drug that has been associated with improved appetite in those with HIV infections and cancer. We completed a two-stage Phase II dose titration study of thalidomide, the primary purpose of which was to assess appetite response to thalidomide in cancer-associated anorexia. Individuals older than 18 years of age with active cancer, loss of appetite by numerical rating scale (NRS), life expectancy of at least four weeks, and Eastern Cooperative Oncology Group performance status of 0-3 were entered into the study. Pretreatment screening included medical history, neurologic examination, and symptoms by NRS and categorical scale (CAT). Patients received 50mg of thalidomide by mouth at bedtime for two weeks. Individuals who did not respond were dose escalated to 100mg at night for two weeks. Assessment of appetite, early satiety, fatigue, insomnia, night sweats, pain, and quality of life (QOL) occurred at two-week intervals. Toxicity also was assessed. The primary outcome was appetite response defined as a two-point reduction in the NRS or a one-point improvement in the CAT. Thirty-five patients entered the study; 33 completed 14 days of therapy and were analyzed for efficacy and toxicity. Sixty-four percent who completed at least two weeks of thalidomide had improved appetite. The CAT scores for appetite, insomnia, and QOL improved significantly. The 95% confidence intervals did not overlap. Five participants dropped out because of toxicity: two before two weeks and three later. Thalidomide reduced multiple symptoms commonly associated with cancer-related anorexia and improved QOL. Our findings confirmed and validated a previously published single-arm trial. A recent randomized trial demonstrated greater benefits when thalidomide is used combined with other agents to treat cancer-associated

  12. Short leukocyte telomere length is associated with obesity in American Indians: the Strong Heart Family study.

    Science.gov (United States)

    Chen, Shufeng; Yeh, Fawn; Lin, Jue; Matsuguchi, Tet; Blackburn, Elizabeth; Lee, Elisa T; Howard, Barbara V; Zhao, Jinying

    2014-05-01

    Shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders including cardiovascular disease (CVD) and diabetes. Obesity is an important risk factor for CVD and diabetes. The association of LTL with obesity is not well understood. This study for the first time examines the association of LTL with obesity indices including body mass index, waist circumference, percent body fat, waist-to-hip ratio, and waist-to-height ratio in 3,256 American Indians (14-93 years old, 60% women) participating in the Strong Heart Family Study. Association of LTL with each adiposity index was examined using multivariate generalized linear mixed model, adjusting for chronological age, sex, study center, education, lifestyle (smoking, alcohol consumption, and total energy intake), high-sensitivity C-reactive protein, hypertension and diabetes. Results show that obese participants had significantly shorter LTL than non-obese individuals (age-adjusted P=0.0002). Multivariate analyses demonstrate that LTL was significantly and inversely associated with all of the studied obesity parameters. Our results may shed light on the potential role of biological aging in pathogenesis of obesity and its comorbidities.

  13. Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

    Directory of Open Access Journals (Sweden)

    Brandon L Pierce

    Full Text Available Arsenic contamination of drinking water is a major public health issue in many countries, increasing risk for a wide array of diseases, including cancer. There is inter-individual variation in arsenic metabolism efficiency and susceptibility to arsenic toxicity; however, the basis of this variation is not well understood. Here, we have performed the first genome-wide association study (GWAS of arsenic-related metabolism and toxicity phenotypes to improve our understanding of the mechanisms by which arsenic affects health. Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs for 1,313 arsenic-exposed Bangladeshi individuals, we identified genome-wide significant association signals (P<5×10(-8 for percentages of both monomethylarsonic acid (MMA and dimethylarsinic acid (DMA near the AS3MT gene (arsenite methyltransferase; 10q24.32, with five genetic variants showing independent associations. In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity and 1,794 controls, we show that one of these five variants (rs9527 is also associated with skin lesion risk (P = 0.0005. Using a subset of individuals with prospectively measured arsenic (n = 769, we show that rs9527 interacts with arsenic to influence incident skin lesion risk (P = 0.01. Expression quantitative trait locus (eQTL analyses of genome-wide expression data from 950 individual's lymphocyte RNA suggest that several of our lead SNPs represent cis-eQTLs for AS3MT (P = 10(-12 and neighboring gene C10orf32 (P = 10(-44, which are involved in C10orf32-AS3MT read-through transcription. This is the largest and most comprehensive genomic investigation of arsenic metabolism and toxicity to date, the only GWAS of any arsenic-related trait, and the first study to implicate 10q24.32 variants in both arsenic metabolism and arsenical

  14. Association study in Alzheimer’s disease of single nucleotide polymorphisms implicated with coffee consumption

    Directory of Open Access Journals (Sweden)

    Victor Junji Yamamoto

    2015-06-01

    Full Text Available Background There is evidence from animal and in vitro models of the protective effects of caffeine in Alzheimer’s disease. The suggested mechanisms through which caffeine may protect neurons against Alzheimer’s disease pathology include the facilitation of beta-amyloid clearance, upregulation of cholinergic transmission, and increased neuronal plasticity and survival. Epidemiological studies support that Alzheimer’s disease patients consume smaller amounts of coffee beverages throughout their lives as compared to age-matched cognitively healthy individuals. Objective The aim of the present study was to determine whether the negative association between Alzheimer’s disease and coffee consumption may be influenced by a common genetic predisposition, given the fact that the pattern of coffee consumption is determined by both environmental and genetic factors. Method We conducted an in silico search addressing the association between genetic polymorphisms related to coffee consumption and the diagnosis of Alzheimer’s disease. We further investigated the interactions between genes located in regions bearing these polymorphisms. Results Our analysis revealed no evidence for a genetic association (nor interaction between related proteins involving coffee consumption and Alzheimer’s disease. Discussion The negative association between Alzheimer’s disease and coffee consumption suggested by epidemiological studies is most likely due to environmental factors that are not necessarily regulated by genetic background.

  15. The Association between Bone Quality and Atherosclerosis: Results from Two Large Population-Based Studies

    Directory of Open Access Journals (Sweden)

    V. Lange

    2017-01-01

    Full Text Available Objective. It is highly debated whether associations between osteoporosis and atherosclerosis are independent of cardiovascular risk factors. We aimed to explore the associations between quantitative ultrasound (QUS parameters at the heel with the carotid artery intima-media thickness (IMT, the presence of carotid artery plaques, and the ankle-brachial index (ABI. Methods. The study population comprised 5680 men and women aged 20–93 years from two population-based cohort studies: Study of Health in Pomerania (SHIP and SHIP-Trend. QUS measurements were performed at the heel. The extracranial carotid arteries were examined with B-mode ultrasonography. ABI was measured in a subgroup of 3853 participants. Analyses of variance and linear and logistic regression models were calculated and adjusted for major cardiovascular risk factors. Results. Men but not women had significantly increased odds for carotid artery plaques with decreasing QUS parameters independent of diabetes mellitus, dyslipidemia, and hypertension. Beyond this, the QUS parameters were not significantly associated with IMT or ABI in fully adjusted models. Conclusions. Our data argue against an independent role of bone metabolism in atherosclerotic changes in women. Yet, in men, associations with advanced atherosclerosis, exist. Thus, men presenting with clinical signs of osteoporosis may be at increased risk for atherosclerotic disease.

  16. The Association between Bone Quality and Atherosclerosis: Results from Two Large Population-Based Studies.

    Science.gov (United States)

    Lange, V; Dörr, M; Schminke, U; Völzke, H; Nauck, M; Wallaschofski, H; Hannemann, A

    2017-01-01

    It is highly debated whether associations between osteoporosis and atherosclerosis are independent of cardiovascular risk factors. We aimed to explore the associations between quantitative ultrasound (QUS) parameters at the heel with the carotid artery intima-media thickness (IMT), the presence of carotid artery plaques, and the ankle-brachial index (ABI). The study population comprised 5680 men and women aged 20-93 years from two population-based cohort studies: Study of Health in Pomerania (SHIP) and SHIP-Trend. QUS measurements were performed at the heel. The extracranial carotid arteries were examined with B-mode ultrasonography. ABI was measured in a subgroup of 3853 participants. Analyses of variance and linear and logistic regression models were calculated and adjusted for major cardiovascular risk factors. Men but not women had significantly increased odds for carotid artery plaques with decreasing QUS parameters independent of diabetes mellitus, dyslipidemia, and hypertension. Beyond this, the QUS parameters were not significantly associated with IMT or ABI in fully adjusted models. Our data argue against an independent role of bone metabolism in atherosclerotic changes in women. Yet, in men, associations with advanced atherosclerosis, exist. Thus, men presenting with clinical signs of osteoporosis may be at increased risk for atherosclerotic disease.

  17. Association between Social Relationship and Glycemic Control among Older Japanese: JAGES Cross-Sectional Study.

    Science.gov (United States)

    Yokobayashi, Kenichi; Kawachi, Ichiro; Kondo, Katsunori; Kondo, Naoki; Nagamine, Yuiko; Tani, Yukako; Shirai, Kokoro; Tazuma, Susumu

    2017-01-01

    The present study examined whether social support, informal socializing and social participation are associated with glycemic control in older people. Data for this population-based cross-sectional study was obtained from the Japan Gerontological Evaluation Study (JAGES) 2010 linked to the annual health check-up data in Japan. We analyzed 9,554 individuals aged ≥65 years without the certification of needed long-term care. Multivariate logistic regression models were used to assess the effect of social support, informal socializing and social participations on glycemic control. The outcome measure was HbA1c ≥8.4%. 1.3% of the participants had a level of HbA1c over 8.4%. Better glycemic control was significantly associated with meeting with friends one to four times per month (odds ratio [OR] 0.51, 95% confidence interval [CI]0.30-0.89, compared to meeting with friends a few times per year or less) and participation in sports groups (OR 0.50, 95% CI 0.26-0.97) even after adjusting for other variables. Meeting with friends more than twice per week, receiving social support, and being married were not associated with better control of diabetes. Meeting with friends occasionally is associated with better glycemic control among older people.

  18. A RETROSPECTIVE STUDY OF BOVINE ABORTIONS ASSOCIATED WITH BACILLUS-LICHENIFORMIS

    DEFF Research Database (Denmark)

    Agerholm, J.S.; Krogh, H.V.; Jensen, H.E.

    1995-01-01

    A retrospective study of bovine abortions associated with Bacillus licheniformis is described. The material consisted of 2445 bovine abortions submitted for diagnostics from 1986 through 1993. Initially, B, licheniformis had been isolated from 81 cases. Sections of these cases were reexamined...... isolations, especially from the placenta, lungs, and abomasal contents, combined with the histological findings points to B, licheniformis abortions as being of haematogenous origin with subsequent transplacental spread to the fetus....

  19. Color-emotion associations and color preferences: A case study for residences

    OpenAIRE

    Manav, Banu

    2007-01-01

    This study examines existing beliefs about "color" focusing on color-emotion associations by discussing how color can be used as a way of communicator to fulfill human needs in residences. Fifty people from various age groups participated in the study. They were asked to match a list of adjectives with the proper color samples from the catalogue of a quite popular color producer firm in Turkey. Results indicate that there is a strong dependency between the choice and use of green at residence...

  20. Association between perceived racial discrimination and hypertension: findings from the ELSA-Brasil study.

    Science.gov (United States)

    Mendes, Patrícia Miranda; Nobre, Aline Araújo; Griep, Rosane Härter; Guimarães, Joanna Miguez Nery; Juvanhol, Leidjaira Lopes; Barreto, Sandhi Maria; Pereira, Alexandre; Chor, Dóra

    2018-03-01

    "Pardos" and blacks in Brazil and blacks in the USA are at greater risk of developing arterial hypertension than whites, and the causes of this inequality are still little understood. Psychosocial and contextual factors, including racial discrimination, are indicated as conditions associated with this inequality. The aim of this study was to identify the association between perceived racial discrimination and hypertension. The study evaluated 14,012 workers from the ELSA-Brazil baseline population. Perceived discrimination was measured by the Lifetime Major Events Scale, adapted to Portuguese. Classification by race/color followed the categories proposed by Brazilian Institute of Geography and Statistics (IBGE). Hypertension was defined by standard criteria. The association between the compound variable - race/racial discrimination - and hypertension was estimated by Poisson regression with robust variance and stratified by the categories of body mass index (BMI) and sex. Choosing white women as the reference group, in the BMI 25kg/m2 and men in any BMI category, no effect of racial discrimination was identified. Despite the differences in point estimates of prevalence of hypertension between "pardo" women who reported and those who did not report discrimination, our results are insufficient to assert that an association exists between racial discrimination and hypertension.

  1. Mineralogical and geological study of fault rocks and associated strata

    International Nuclear Information System (INIS)

    Kim, Jeon Jin; Jeong, Gyo Cheol; Bae, Doo Won; Park, Seong Min; Kim, Jun Yeong

    2007-01-01

    Mineralogical characterizations of fault clay and associated strata in fault zone with field study and analytical methods. Mineral composition and color of fault clay and rock occur in fracture zone different from bed rocks. Fault clay mainly composed of smectite with minor zeolite such as laumontite and stilbite, and halloysite, illite, Illite and halloysite grow on the surface of smectite, and laumontite and stilbite result from precipitation or alteration of Ca rich bed rock. The result of mineralogical study at Ipsil, Wangsan, Gaegok, Yugyeori, Gacheon in Gyeongju area, the detail research of microstructure in the fault clay making it possible for prediction to age of fault activity

  2. Mineralogical and geological study of fault rocks and associated strata

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeon Jin; Jeong, Gyo Cheol; Bae, Doo Won; Park, Seong Min; Kim, Jun Yeong [Andong Univ., Andong (Korea, Republic of)

    2007-01-15

    Mineralogical characterizations of fault clay and associated strata in fault zone with field study and analytical methods. Mineral composition and color of fault clay and rock occur in fracture zone different from bed rocks. Fault clay mainly composed of smectite with minor zeolite such as laumontite and stilbite, and halloysite, illite, Illite and halloysite grow on the surface of smectite, and laumontite and stilbite result from precipitation or alteration of Ca rich bed rock. The result of mineralogical study at Ipsil, Wangsan, Gaegok, Yugyeori, Gacheon in Gyeongju area, the detail research of microstructure in the fault clay making it possible for prediction to age of fault activity.

  3. Genome-wide association study identified CNP12587 region underlying height variation in Chinese females.

    Directory of Open Access Journals (Sweden)

    Yin-Ping Zhang

    Full Text Available Human height is a highly heritable trait considered as an important factor for health. There has been limited success in identifying the genetic factors underlying height variation. We aim to identify sequence variants associated with adult height by a genome-wide association study of copy number variants (CNVs in Chinese.Genome-wide CNV association analyses were conducted in 1,625 unrelated Chinese adults and sex specific subgroup for height variation, respectively. Height was measured with a stadiometer. Affymetrix SNP6.0 genotyping platform was used to identify copy number polymorphisms (CNPs. We constructed a genomic map containing 1,009 CNPs in Chinese individuals and performed a genome-wide association study of CNPs with height.We detected 10 significant association signals for height (p<0.05 in the whole population, 9 and 11 association signals for Chinese female and male population, respectively. A copy number polymorphism (CNP12587, chr18:54081842-54086942, p = 2.41 × 10(-4 was found to be significantly associated with height variation in Chinese females even after strict Bonferroni correction (p = 0.048. Confirmatory real time PCR experiments lent further support for CNV validation. Compared to female subjects with two copies of the CNP, carriers of three copies had an average of 8.1% decrease in height. An important candidate gene, ubiquitin-protein ligase NEDD4-like (NEDD4L, was detected at this region, which plays important roles in bone metabolism by binding to bone formation regulators.Our findings suggest the important genetic variants underlying height variation in Chinese.

  4. Serum testosterone levels in males are not associated with entrepreneurial behavior in two independent observational studies.

    Science.gov (United States)

    van der Loos, Matthijs J H M; Haring, Robin; Rietveld, Cornelius A; Baumeister, Sebastian E; Groenen, Patrick J F; Hofman, Albert; de Jong, Frank H; Koellinger, Philipp D; Kohlmann, Thomas; Nauck, Matthias A; Rivadeneira, Fernando; Uitterlinden, André G; van Rooij, Frank J A; Wallaschofski, Henri; Thurik, A Roy

    2013-07-02

    Previous research has suggested a positive association between testosterone (T) and entrepreneurial behavior in males. However, this evidence was found in a study with a small sample size and has not been replicated. In the present study, we aimed to verify this association using two large, independent, population-based samples of males. We tested the association of T with entrepreneurial behavior, operationalized as self-employment, using data from the Rotterdam Study (N=587) and the Study of Health in Pomerania (N=1697). Total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured in the serum. Free testosterone (FT), non-SHBG-bound T (non-SHBG-T), and the TT/SHBG ratio were calculated and used as measures of bioactive serum T, in addition to TT adjusted for SHBG. Using logistic regression models, we found no significant associations between any of the serum T measures and self-employment in either of the samples. To our knowledge, this is the first large-scale study on the relationship between serum T and entrepreneurial behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Proportion of medication error reporting and associated factors among nurses: a cross sectional study.

    Science.gov (United States)

    Jember, Abebaw; Hailu, Mignote; Messele, Anteneh; Demeke, Tesfaye; Hassen, Mohammed

    2018-01-01

    A medication error (ME) is any preventable event that may cause or lead to inappropriate medication use or patient harm. Voluntary reporting has a principal role in appreciating the extent and impact of medication errors. Thus, exploration of the proportion of medication error reporting and associated factors among nurses is important to inform service providers and program implementers so as to improve the quality of the healthcare services. Institution based quantitative cross-sectional study was conducted among 397 nurses from March 6 to May 10, 2015. Stratified sampling followed by simple random sampling technique was used to select the study participants. The data were collected using structured self-administered questionnaire which was adopted from studies conducted in Australia and Jordan. A pilot study was carried out to validate the questionnaire before data collection for this study. Bivariate and multivariate logistic regression models were fitted to identify factors associated with the proportion of medication error reporting among nurses. An adjusted odds ratio with 95% confidence interval was computed to determine the level of significance. The proportion of medication error reporting among nurses was found to be 57.4%. Regression analysis showed that sex, marital status, having made a medication error and medication error experience were significantly associated with medication error reporting. The proportion of medication error reporting among nurses in this study was found to be higher than other studies.

  6. Genome-wide association study of Tourette Syndrome

    Science.gov (United States)

    Scharf, Jeremiah M.; Yu, Dongmei; Mathews, Carol A.; Neale, Benjamin M.; Stewart, S. Evelyn; Fagerness, Jesen A; Evans, Patrick; Gamazon, Eric; Edlund, Christopher K.; Service, Susan; Tikhomirov, Anna; Osiecki, Lisa; Illmann, Cornelia; Pluzhnikov, Anna; Konkashbaev, Anuar; Davis, Lea K; Han, Buhm; Crane, Jacquelyn; Moorjani, Priya; Crenshaw, Andrew T.; Parkin, Melissa A.; Reus, Victor I.; Lowe, Thomas L.; Rangel-Lugo, Martha; Chouinard, Sylvain; Dion, Yves; Girard, Simon; Cath, Danielle C; Smit, Jan H; King, Robert A.; Fernandez, Thomas; Leckman, James F.; Kidd, Kenneth K.; Kidd, Judith R.; Pakstis, Andrew J.; State, Matthew; Herrera, Luis Diego; Romero, Roxana; Fournier, Eduardo; Sandor, Paul; Barr, Cathy L; Phan, Nam; Gross-Tsur, Varda; Benarroch, Fortu; Pollak, Yehuda; Budman, Cathy L.; Bruun, Ruth D.; Erenberg, Gerald; Naarden, Allan L; Lee, Paul C; Weiss, Nicholas; Kremeyer, Barbara; Berrío, Gabriel Bedoya; Campbell, Desmond; Silgado, Julio C. Cardona; Ochoa, William Cornejo; Restrepo, Sandra C. Mesa; Muller, Heike; Duarte, Ana V. Valencia; Lyon, Gholson J; Leppert, Mark; Morgan, Jubel; Weiss, Robert; Grados, Marco A.; Anderson, Kelley; Davarya, Sarah; Singer, Harvey; Walkup, John; Jankovic, Joseph; Tischfield, Jay A.; Heiman, Gary A.; Gilbert, Donald L.; Hoekstra, Pieter J.; Robertson, Mary M.; Kurlan, Roger; Liu, Chunyu; Gibbs, J. Raphael; Singleton, Andrew; Hardy, John; Strengman, Eric; Ophoff, Roel; Wagner, Michael; Moessner, Rainald; Mirel, Daniel B.; Posthuma, Danielle; Sabatti, Chiara; Eskin, Eleazar; Conti, David V.; Knowles, James A.; Ruiz-Linares, Andres; Rouleau, Guy A.; Purcell, Shaun; Heutink, Peter; Oostra, Ben A.; McMahon, William; Freimer, Nelson; Cox, Nancy J.; Pauls, David L.

    2012-01-01

    Tourette Syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel, and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (p<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (p=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely-related Latin-American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (p=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder. PMID:22889924

  7. 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.

  8. 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.

  9. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies

    DEFF Research Database (Denmark)

    Bulik-Sullivan, Brendan K.; Loh, Po-Ru; Finucane, Hilary K.

    2015-01-01

    Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from...

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

    Science.gov (United States)

    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.

  11. Association between protozoa in sputum and asthma: a case-control study.

    Science.gov (United States)

    van Woerden, Hugo C; Ratier-Cruz, Adriana; Aleshinloye, Olabode B; Martinez-Giron, Rafael; Gregory, Clive; Matthews, Ian P

    2011-06-01

    Atypical infectious agents have been proposed as potential contributors to asthma. A novel set of morphological and staining criteria permit the identification of flagellated protozoa in sputum. This case-control study was designed to use this novel method and to assess: (1) are protozoa more common in asthmatics than in non-asthmatics; (2) is the presence of protozoa associated with the use of steroid inhalers; and (3) is the presence of protozoa associated with living in damp housing? Induced sputum samples were collected from asthma patients and local non-atopic, non-smoking controls. Questionnaires assessed asthma severity and housing conditions. Sputum was examined for flagellated protozoa using a previously described staining technique. 96 participants were recruited for this study; 54 asthma patients and 42 controls, age range 21-62 years, 70% female participants. Limiting results to those who were clearly positive or negative for flagellated protozoa, 66.7% (20/30) of asthmatics and 30.8% (4/13) of controls had protozoa (p = 0.046). Among the asthma patients, prevalence of protozoa was not significantly different between those who had (10/18), and those who had not (10/12), used steroid inhaler in the preceding two weeks (p = 0.11). Similarly, the prevalence of protozoa was not significantly different between those who did (6/11) and those who did not (18/32), live in damp homes (p = 0.92). This case-control study demonstrates an association between flagellated protozoa in sputum and asthma. It is now necessary to confirm and characterise the protozoa using genetic techniques based on 18S ribosomal RNA. Once tis is established it would be worthwhile to determine if asthma symptoms improve when treated by anti-protozoal agents. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. A Longitudinal Study of Association between Adiposity Markers and Intraocular Pressure: The Kangbuk Samsung Health Study.

    Science.gov (United States)

    Zhao, Di; Kim, Myung Hun; Pastor-Barriuso, Roberto; Chang, Yoosoo; Ryu, Seungho; Zhang, Yiyi; Rampal, Sanjay; Shin, Hocheol; Kim, Joon Mo; Friedman, David S; Guallar, Eliseo; Cho, Juhee

    2016-01-01

    Intraocular pressure (IOP) reduction or stabilization is the only proven method for glaucoma management. Identifying risk factors for IOP is crucial to understand the pathophysiology of glaucoma. To examine the associations of change in body mass index (BMI), waist circumference, and percent fat mass with change in intraocular pressure (IOP) in a large sample of Korean adults. Cohort study of 274,064 young and middle age Korean adults with normal fundoscopic findings who attended annual or biennial health exams from January 1, 2002 to Feb 28, 2010 (577,981 screening visits). BMI, waist circumference, and percent fat mass. At each visit, IOP was measured in both eyes with automated noncontact tonometers. In multivariable-adjusted models, the average increase in IOP (95% confidence intervals) over time per interquartile increase in BMI (1.26 kg/m2), waist circumference (6.20 cm), and percent fat mass (3.40%) were 0.18 mmHg (0.17 to 0.19), 0.27 mmHg (0.26 to 0.29), and 0.10 mmHg (0.09 to 0.11), respectively (all P < 0.001). The association was stronger in men compared to women (P < 0.001) and it was only slightly attenuated after including diabetes and hypertension as potential mediators in the model. Increases in adiposity were significantly associated with an increase in IOP in a large cohort of Korean adults attending health screening visits, an association that was stronger for central obesity. Further research is needed to understand better the underlying mechanisms of this association, and to establish the role of weight gain in increasing IOP and the risk of glaucoma and its complications.

  13. A Longitudinal Study of Association between Adiposity Markers and Intraocular Pressure: The Kangbuk Samsung Health Study.

    Directory of Open Access Journals (Sweden)

    Di Zhao

    Full Text Available Intraocular pressure (IOP reduction or stabilization is the only proven method for glaucoma management. Identifying risk factors for IOP is crucial to understand the pathophysiology of glaucoma.To examine the associations of change in body mass index (BMI, waist circumference, and percent fat mass with change in intraocular pressure (IOP in a large sample of Korean adults.Cohort study of 274,064 young and middle age Korean adults with normal fundoscopic findings who attended annual or biennial health exams from January 1, 2002 to Feb 28, 2010 (577,981 screening visits.BMI, waist circumference, and percent fat mass.At each visit, IOP was measured in both eyes with automated noncontact tonometers.In multivariable-adjusted models, the average increase in IOP (95% confidence intervals over time per interquartile increase in BMI (1.26 kg/m2, waist circumference (6.20 cm, and percent fat mass (3.40% were 0.18 mmHg (0.17 to 0.19, 0.27 mmHg (0.26 to 0.29, and 0.10 mmHg (0.09 to 0.11, respectively (all P < 0.001. The association was stronger in men compared to women (P < 0.001 and it was only slightly attenuated after including diabetes and hypertension as potential mediators in the model.Increases in adiposity were significantly associated with an increase in IOP in a large cohort of Korean adults attending health screening visits, an association that was stronger for central obesity. Further research is needed to understand better the underlying mechanisms of this association, and to establish the role of weight gain in increasing IOP and the risk of glaucoma and its complications.

  14. [Pregnancy-Associated Breast Cancer: An analytical observational study].

    Science.gov (United States)

    Baulies, Sonia; Cusidó, Maite; Tresserra, Francisco; Rodríguez, Ignacio; Ubeda, Belén; Ara, Carmen; Fábregas, Rafael

    2014-03-04

    Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy and up to one year postpartum. A retrospective, analytical, observational study comparing 56 cases of breast cancer and pregnancy (PABC) diagnosed 1976-2008 with 73 patients with breast cancer not associated with pregnancy (non-PABC) was performed. Demographic data, prognostic factors, treatment and survival were reviewed and compared. The prevalence of PABC in our center is 8.3/10,000. The highest frequency (62%) appeared during the postpartum period. The stages are higher in PABC, being 31.3% advanced (EIII and EIV) in PABC versus 13.3% in non-PABC (P < .05). Regarding prognostic factors, 27.3% in PABC had a tumoral grade 3 versus 15.8% of non-PABC. Among women with PABC, 33.3% had negative estrogen receptors, 48.7% negative progesterone receptors and 34.5% positive Her2Neu compared with 22.2, 24.1 and 31%, respectively of non-PABC patients. Finally, positive lymph nodes were found in 52.8% of PABC, versus 33.8% non-PABC (P < .05). Overall and disease-free survival rate at 5 years for PABC was 63.7 and 74.2%, respectively. The poorer survival observed is possibly due to the presence of adverse prognostic features such as lymph node metastases, negative hormone receptors, tumoral grade iii, as well as a delay in diagnosis with a higher rate of advanced stages. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  15. Microbial genome-wide association studies: lessons from human GWAS.

    Science.gov (United States)

    Power, Robert A; Parkhill, Julian; de Oliveira, Tulio

    2017-01-01

    The reduced costs of sequencing have led to whole-genome sequences for a large number of microorganisms, enabling the application of microbial genome-wide association studies (GWAS). Given the successes of human GWAS in understanding disease aetiology and identifying potential drug targets, microbial GWAS are likely to further advance our understanding of infectious diseases. These advances include insights into pressing global health problems, such as antibiotic resistance and disease transmission. In this Review, we outline the methodologies of GWAS, the current state of the field of microbial GWAS, and how lessons from human GWAS can direct the future of the field.

  16. 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.

  17. Genome-wide association study identifies candidate genes for starch content regulation in maize kernels

    Directory of Open Access Journals (Sweden)

    Na Liu

    2016-07-01

    Full Text Available Kernel starch content is an important trait in maize (Zea mays L. as it accounts for 65% to 75% of the dry kernel weight and positively correlates with seed yield. A number of starch synthesis-related genes have been identified in maize in recent years. However, many loci underlying variation in starch content among maize inbred lines still remain to be identified. The current study is a genome-wide association study that used a set of 263 maize inbred lines. In this panel, the average kernel starch content was 66.99%, ranging from 60.60% to 71.58% over the three study years. These inbred lines were genotyped with the SNP50 BeadChip maize array, which is comprised of 56,110 evenly spaced, random SNPs. Population structure was controlled by a mixed linear model (MLM as implemented in the software package TASSEL. After the statistical analyses, four SNPs were identified as significantly associated with starch content (P ≤ 0.0001, among which one each are located on chromosomes 1 and 5 and two are on chromosome 2. Furthermore, 77 candidate genes associated with starch synthesis were found within the 100-kb intervals containing these four QTLs, and four highly associated genes were within 20-kb intervals of the associated SNPs. Among the four genes, Glucose-1-phosphate adenylyltransferase (APS1; Gene ID GRMZM2G163437 is known as an important regulator of kernel starch content. The identified SNPs, QTLs, and candidate genes may not only be readily used for germplasm improvement by marker-assisted selection in breeding, but can also elucidate the genetic basis of starch content. Further studies on these identified candidate genes may help determine the molecular mechanisms regulating kernel starch content in maize and other important cereal crops.

  18. Gut Microbiome Associates With Lifetime Cardiovascular Disease Risk Profile Among Bogalusa Heart Study Participants.

    Science.gov (United States)

    Kelly, Tanika N; Bazzano, Lydia A; Ajami, Nadim J; He, Hua; Zhao, Jinying; Petrosino, Joseph F; Correa, Adolfo; He, Jiang

    2016-09-30

    Few studies have systematically assessed the influence of gut microbiota on cardiovascular disease (CVD) risk. To examine the association between gut microbiota and lifetime CVD risk profile among 55 Bogalusa Heart Study participants with the highest and 57 with the lowest lifetime burdens of CVD risk factors. 16S ribosomal RNA sequencing was conducted on microbial DNA extracted from stool samples of the Bogalusa Heart Study participants. α Diversity, including measures of richness and evenness, and individual genera were tested for associations with lifetime CVD risk profile. Multivariable regression techniques were used to adjust for age, sex, and race (model 1), along with body mass index (model 2) and both body mass index and diet (model 3). In model 1, odds ratios (95% confidence intervals) for each SD increase in richness, measured by the number of observed operational taxonomic units, Chao 1 index, and abundance-based coverage estimator, were 0.62 (0.39-0.99), 0.61 (0.38-0.98), and 0.63 (0.39-0.99), respectively. Associations were consistent in models 2 and 3. Four genera were enriched among those with high versus low CVD risk profile in all models. Model 1 P values were 2.12×10(-3), 7.95×10(-5), 4.39×10(-4), and 1.51×10(-4) for Prevotella 2, Prevotella 7, Tyzzerella, and Tyzzerella 4, respectively. Two genera were depleted among those with high versus low CVD risk profile in all models. Model 1 P values were 2.96×10(-6) and 1.82×10(-4) for Alloprevotella and Catenibacterium, respectively. The current study identified associations of overall microbial richness and 6 microbial genera with lifetime CVD risk. © 2016 American Heart Association, Inc.

  19. Associations between VO2max and vitality in older workers: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    van der Beek Allard J

    2010-11-01

    Full Text Available Abstract Background To prevent early exit from work, it is important to study which factors contribute to healthy ageing. One concept that is assumed to be closely related to, and therefore may influence healthy ageing, is vitality. Vitality consists of both a mental and a physical component, and is characterised by a perceived high energy level, decreased feelings of fatigue, and feeling fit. Since VO2max gives an indication of one's aerobic fitness, which can be improved by increased levels of physical activity, and because feeling fit is one of the main characteristics of vitality, it is hypothesised that VO2max is related to vitality. Therefore, the aim of this study was to investigate the associations between VO2max and vitality. Methods In 427 older workers (aged 45 + years participating in the Vital@Work study, VO2max was estimated at baseline using the 2-km UKK walk test. Vitality was measured by both the UWES Vitality Scale and the RAND-36 Vitality Scale. Associations were analysed using linear regression analyses. Results The linear regression models, adjusted for age, showed a significant association between VO2max and vitality measured with the RAND-36 Vitality Scale (β = 0.446; 95% CI: 0.220-0.673. There was no significant association between VO2max and vitality measured with the UWES (β = -0.006; 95% CI:-0.017 - 0.006, after adjusting for age, gender and chronic disease status. Conclusions VO2max was associated with a general measure of vitality (measured with the RAND-36 Vitality Scale, but not with occupational health related vitality (measured with the UWES Vitality Scale. The idea that physical exercise can be used as an effective tool for improving vitality was supported in this study. Trial registration NTR1240

  20. Associations between VO2max and vitality in older workers: a cross-sectional study.

    Science.gov (United States)

    Strijk, Jorien E; Proper, Karin I; Klaver, Linda; van der Beek, Allard J; van Mechelen, Willem

    2010-11-09

    To prevent early exit from work, it is important to study which factors contribute to healthy ageing. One concept that is assumed to be closely related to, and therefore may influence healthy ageing, is vitality. Vitality consists of both a mental and a physical component, and is characterised by a perceived high energy level, decreased feelings of fatigue, and feeling fit. Since VO2max gives an indication of one's aerobic fitness, which can be improved by increased levels of physical activity, and because feeling fit is one of the main characteristics of vitality, it is hypothesised that VO2max is related to vitality. Therefore, the aim of this study was to investigate the associations between VO2max and vitality. In 427 older workers (aged 45 + years) participating in the Vital@Work study, VO2max was estimated at baseline using the 2-km UKK walk test. Vitality was measured by both the UWES Vitality Scale and the RAND-36 Vitality Scale. Associations were analysed using linear regression analyses. The linear regression models, adjusted for age, showed a significant association between VO2max and vitality measured with the RAND-36 Vitality Scale (β = 0.446; 95% CI: 0.220-0.673). There was no significant association between VO2max and vitality measured with the UWES (β = -0.006; 95% CI:-0.017 - 0.006), after adjusting for age, gender and chronic disease status. VO2max was associated with a general measure of vitality (measured with the RAND-36 Vitality Scale), but not with occupational health related vitality (measured with the UWES Vitality Scale). The idea that physical exercise can be used as an effective tool for improving vitality was supported in this study. NTR1240.