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Sample records for gene expression meta-analysis

  1. Meta Analysis of Gene Expression Data within and Across Species.

    Science.gov (United States)

    Fierro, Ana C; Vandenbussche, Filip; Engelen, Kristof; Van de Peer, Yves; Marchal, Kathleen

    2008-12-01

    Since the second half of the 1990s, a large number of genome-wide analyses have been described that study gene expression at the transcript level. To this end, two major strategies have been adopted, a first one relying on hybridization techniques such as microarrays, and a second one based on sequencing techniques such as serial analysis of gene expression (SAGE), cDNA-AFLP, and analysis based on expressed sequence tags (ESTs). Despite both types of profiling experiments becoming routine techniques in many research groups, their application remains costly and laborious. As a result, the number of conditions profiled in individual studies is still relatively small and usually varies from only two to few hundreds of samples for the largest experiments. More and more, scientific journals require the deposit of these high throughput experiments in public databases upon publication. Mining the information present in these databases offers molecular biologists the possibility to view their own small-scale analysis in the light of what is already available. However, so far, the richness of the public information remains largely unexploited. Several obstacles such as the correct association between ESTs and microarray probes with the corresponding gene transcript, the incompleteness and inconsistency in the annotation of experimental conditions, and the lack of standardized experimental protocols to generate gene expression data, all impede the successful mining of these data. Here, we review the potential and difficulties of combining publicly available expression data from respectively EST analyses and microarray experiments. With examples from literature, we show how meta-analysis of expression profiling experiments can be used to study expression behavior in a single organism or between organisms, across a wide range of experimental conditions. We also provide an overview of the methods and tools that can aid molecular biologists in exploiting these public data.

  2. A resampling-based meta-analysis for detection of differential gene expression in breast cancer

    International Nuclear Information System (INIS)

    Gur-Dedeoglu, Bala; Konu, Ozlen; Kir, Serkan; Ozturk, Ahmet Rasit; Bozkurt, Betul; Ergul, Gulusan; Yulug, Isik G

    2008-01-01

    Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures. A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis. The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively). The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real-time qRT-PCR supported the meta-analysis results. The

  3. A resampling-based meta-analysis for detection of differential gene expression in breast cancer

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    Ergul Gulusan

    2008-12-01

    Full Text Available Abstract Background Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures. Methods A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC, and invasive lobular carcinoma (ILC samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis. Results The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively. The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real

  4. Bayesian models and meta analysis for multiple tissue gene expression data following corticosteroid administration

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    Kelemen Arpad

    2008-08-01

    Full Text Available Abstract Background This paper addresses key biological problems and statistical issues in the analysis of large gene expression data sets that describe systemic temporal response cascades to therapeutic doses in multiple tissues such as liver, skeletal muscle, and kidney from the same animals. Affymetrix time course gene expression data U34A are obtained from three different tissues including kidney, liver and muscle. Our goal is not only to find the concordance of gene in different tissues, identify the common differentially expressed genes over time and also examine the reproducibility of the findings by integrating the results through meta analysis from multiple tissues in order to gain a significant increase in the power of detecting differentially expressed genes over time and to find the differential differences of three tissues responding to the drug. Results and conclusion Bayesian categorical model for estimating the proportion of the 'call' are used for pre-screening genes. Hierarchical Bayesian Mixture Model is further developed for the identifications of differentially expressed genes across time and dynamic clusters. Deviance information criterion is applied to determine the number of components for model comparisons and selections. Bayesian mixture model produces the gene-specific posterior probability of differential/non-differential expression and the 95% credible interval, which is the basis for our further Bayesian meta-inference. Meta-analysis is performed in order to identify commonly expressed genes from multiple tissues that may serve as ideal targets for novel treatment strategies and to integrate the results across separate studies. We have found the common expressed genes in the three tissues. However, the up/down/no regulations of these common genes are different at different time points. Moreover, the most differentially expressed genes were found in the liver, then in kidney, and then in muscle.

  5. Meta-analysis of gene expression signatures defining the epithelial to mesenchymal transition during cancer progression.

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    Christian J Gröger

    Full Text Available The epithelial to mesenchymal transition (EMT represents a crucial event during cancer progression and dissemination. EMT is the conversion of carcinoma cells from an epithelial to a mesenchymal phenotype that associates with a higher cell motility as well as enhanced chemoresistance and cancer stemness. Notably, EMT has been increasingly recognized as an early event of metastasis. Numerous gene expression studies (GES have been conducted to obtain transcriptome signatures and marker genes to understand the regulatory mechanisms underlying EMT. Yet, no meta-analysis considering the multitude of GES of EMT has been performed to comprehensively elaborate the core genes in this process. Here we report the meta-analysis of 18 independent and published GES of EMT which focused on different cell types and treatment modalities. Computational analysis revealed clustering of GES according to the type of treatment rather than to cell type. GES of EMT induced via transforming growth factor-β and tumor necrosis factor-α treatment yielded uniformly defined clusters while GES of models with alternative EMT induction clustered in a more complex fashion. In addition, we identified those up- and downregulated genes which were shared between the multitude of GES. This core gene list includes well known EMT markers as well as novel genes so far not described in this process. Furthermore, several genes of the EMT-core gene list significantly correlated with impaired pathological complete response in breast cancer patients. In conclusion, this meta-analysis provides a comprehensive survey of available EMT expression signatures and shows fundamental insights into the mechanisms that are governing carcinoma progression.

  6. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    International Nuclear Information System (INIS)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben A

    2008-01-01

    Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent studies. Besides classification of outcome, these global expression patterns may reflect biological mechanisms involved in metastasis of breast cancer. Our purpose has been to investigate pathways and transcription factors involved in metastasis by use of gene expression data sets. We have analyzed 8 publicly available gene expression data sets. A global approach, 'gene set enrichment analysis' as well as an approach focusing on a subset of significantly differently regulated genes, GenMAPP, has been applied to rank pathway gene sets according to differential regulation in metastasizing tumors compared to non-metastasizing tumors. Meta-analysis has been used to determine overrepresentation of pathways and transcription factors targets, concordant deregulated in metastasizing breast tumors, in several data sets. The major findings are up-regulation of cell cycle pathways and a metabolic shift towards glucose metabolism reflected in several pathways in metastasizing tumors. Growth factor pathways seem to play dual roles; EGF and PDGF pathways are decreased, while VEGF and sex-hormone pathways are increased in tumors that metastasize. Furthermore, migration, proteasome, immune system, angiogenesis, DNA repair and several signal transduction pathways are associated to metastasis. Finally several transcription factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis. By pathway meta-analysis many biological mechanisms beyond major characteristics such as proliferation are identified. Transcription factor analysis identifies a number of key factors that support central pathways. Several previously proposed treatment targets are identified and several new pathways that may

  7. Microarray meta-analysis to explore abiotic stress-specific gene expression patterns in Arabidopsis.

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    Shen, Po-Chih; Hour, Ai-Ling; Liu, Li-Yu Daisy

    2017-12-01

    Abiotic stresses are the major limiting factors that affect plant growth, development, yield and final quality. Deciphering the underlying mechanisms of plants' adaptations to stresses using few datasets might overlook the different aspects of stress tolerance in plants, which might be simultaneously and consequently operated in the system. Fortunately, the accumulated microarray expression data offer an opportunity to infer abiotic stress-specific gene expression patterns through meta-analysis. In this study, we propose to combine microarray gene expression data under control, cold, drought, heat, and salt conditions and determined modules (gene sets) of genes highly associated with each other according to the observed expression data. By analyzing the expression variations of the Eigen genes from different conditions, we had identified two, three, and five gene modules as cold-, heat-, and salt-specific modules, respectively. Most of the cold- or heat-specific modules were differentially expressed to a particular degree in shoot samples, while most of the salt-specific modules were differentially expressed to a particular degree in root samples. A gene ontology (GO) analysis on the stress-specific modules suggested that the gene modules exclusively enriched stress-related GO terms and that different genes under the same GO terms may be alternatively disturbed in different conditions. The gene regulatory events for two genes, DREB1A and DEAR1, in the cold-specific gene module had also been validated, as evidenced through the literature search. Our protocols study the specificity of the gene modules that were specifically activated under a particular type of abiotic stress. The biplot can also assist to visualize the stress-specific gene modules. In conclusion, our approach has the potential to further elucidate mechanisms in plants and beneficial for future experiments design under different abiotic stresses.

  8. A meta-analysis of gene expression signatures of blood pressure and hypertension.

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    Tianxiao Huan

    2015-03-01

    Full Text Available Genome-wide association studies (GWAS have uncovered numerous genetic variants (SNPs that are associated with blood pressure (BP. Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05. Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2. Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension.

  9. Transcriptomic meta-analysis identifies gene expression characteristics in various samples of HIV-infected patients with nonprogressive disease.

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    Zhang, Le-Le; Zhang, Zi-Ning; Wu, Xian; Jiang, Yong-Jun; Fu, Ya-Jing; Shang, Hong

    2017-09-12

    A small proportion of HIV-infected patients remain clinically and/or immunologically stable for years, including elite controllers (ECs) who have undetectable viremia (10 years). However, the mechanism of nonprogression needs to be further resolved. In this study, a transcriptome meta-analysis was performed on nonprogressor and progressor microarray data to identify differential transcriptome pathways and potential biomarkers. Using the INMEX (integrative meta-analysis of expression data) program, we performed the meta-analysis to identify consistently differentially expressed genes (DEGs) in nonprogressors and further performed functional interpretation (gene ontology analysis and pathway analysis) of the DEGs identified in the meta-analysis. Five microarray datasets (81 cases and 98 controls in total), including whole blood, CD4 + and CD8 + T cells, were collected for meta-analysis. We determined that nonprogressors have reduced expression of important interferon-stimulated genes (ISGs), CD38, lymphocyte activation gene 3 (LAG-3) in whole blood, CD4 + and CD8 + T cells. Gene ontology (GO) analysis showed a significant enrichment in DEGs that function in the type I interferon signaling pathway. Upregulated pathways, including the PI3K-Akt signaling pathway in whole blood, cytokine-cytokine receptor interaction in CD4 + T cells and the MAPK signaling pathway in CD8 + T cells, were identified in nonprogressors compared with progressors. In each metabolic functional category, the number of downregulated DEGs was more than the upregulated DEGs, and almost all genes were downregulated DEGs in the oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle in the three types of samples. Our transcriptomic meta-analysis provides a comprehensive evaluation of the gene expression profiles in major blood types of nonprogressors, providing new insights in the understanding of HIV pathogenesis and developing strategies to delay HIV disease progression.

  10. dbMDEGA: a database for meta-analysis of differentially expressed genes in autism spectrum disorder.

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    Zhang, Shuyun; Deng, Libin; Jia, Qiyue; Huang, Shaoting; Gu, Junwang; Zhou, Fankun; Gao, Meng; Sun, Xinyi; Feng, Chang; Fan, Guangqin

    2017-11-16

    Autism spectrum disorders (ASD) are hereditary, heterogeneous and biologically complex neurodevelopmental disorders. Individual studies on gene expression in ASD cannot provide clear consensus conclusions. Therefore, a systematic review to synthesize the current findings from brain tissues and a search tool to share the meta-analysis results are urgently needed. Here, we conducted a meta-analysis of brain gene expression profiles in the current reported human ASD expression datasets (with 84 frozen male cortex samples, 17 female cortex samples, 32 cerebellum samples and 4 formalin fixed samples) and knock-out mouse ASD model expression datasets (with 80 collective brain samples). Then, we applied R language software and developed an interactive shared and updated database (dbMDEGA) displaying the results of meta-analysis of data from ASD studies regarding differentially expressed genes (DEGs) in the brain. This database, dbMDEGA ( https://dbmdega.shinyapps.io/dbMDEGA/ ), is a publicly available web-portal for manual annotation and visualization of DEGs in the brain from data from ASD studies. This database uniquely presents meta-analysis values and homologous forest plots of DEGs in brain tissues. Gene entries are annotated with meta-values, statistical values and forest plots of DEGs in brain samples. This database aims to provide searchable meta-analysis results based on the current reported brain gene expression datasets of ASD to help detect candidate genes underlying this disorder. This new analytical tool may provide valuable assistance in the discovery of DEGs and the elucidation of the molecular pathogenicity of ASD. This database model may be replicated to study other disorders.

  11. Meta-analysis of differentiating mouse embryonic stem cell gene expression kinetics reveals early change of a small gene set.

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    Clive H Glover

    2006-11-01

    Full Text Available Stem cell differentiation involves critical changes in gene expression. Identification of these should provide endpoints useful for optimizing stem cell propagation as well as potential clues about mechanisms governing stem cell maintenance. Here we describe the results of a new meta-analysis methodology applied to multiple gene expression datasets from three mouse embryonic stem cell (ESC lines obtained at specific time points during the course of their differentiation into various lineages. We developed methods to identify genes with expression changes that correlated with the altered frequency of functionally defined, undifferentiated ESC in culture. In each dataset, we computed a novel statistical confidence measure for every gene which captured the certainty that a particular gene exhibited an expression pattern of interest within that dataset. This permitted a joint analysis of the datasets, despite the different experimental designs. Using a ranking scheme that favored genes exhibiting patterns of interest, we focused on the top 88 genes whose expression was consistently changed when ESC were induced to differentiate. Seven of these (103728_at, 8430410A17Rik, Klf2, Nr0b1, Sox2, Tcl1, and Zfp42 showed a rapid decrease in expression concurrent with a decrease in frequency of undifferentiated cells and remained predictive when evaluated in additional maintenance and differentiating protocols. Through a novel meta-analysis, this study identifies a small set of genes whose expression is useful for identifying changes in stem cell frequencies in cultures of mouse ESC. The methods and findings have broader applicability to understanding the regulation of self-renewal of other stem cell types.

  12. Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes.

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    Kevin P Keegan

    2007-11-01

    Full Text Available Five independent groups have reported microarray studies that identify dozens of rhythmically expressed genes in the fruit fly Drosophila melanogaster. Limited overlap among the lists of discovered genes makes it difficult to determine which, if any, exhibit truly rhythmic patterns of expression. We reanalyzed data from all five reports and found two sources for the observed discrepancies, the use of different expression pattern detection algorithms and underlying variation among the datasets. To improve upon the methods originally employed, we developed a new analysis that involves compilation of all existing data, application of identical transformation and standardization procedures followed by ANOVA-based statistical prescreening, and three separate classes of post hoc analysis: cross-correlation to various cycling waveforms, autocorrelation, and a previously described fast Fourier transform-based technique. Permutation-based statistical tests were used to derive significance measures for all post hoc tests. We find application of our method, most significantly the ANOVA prescreening procedure, significantly reduces the false discovery rate relative to that observed among the results of the original five reports while maintaining desirable statistical power. We identify a set of 81 cycling transcripts previously found in one or more of the original reports as well as a novel set of 133 transcripts not found in any of the original studies. We introduce a novel analysis method that compensates for variability observed among the original five Drosophila circadian array reports. Based on the statistical fidelity of our meta-analysis results, and the results of our initial validation experiments (quantitative RT-PCR, we predict many of our newly found genes to be bona fide cyclers, and suggest that they may lead to new insights into the pathways through which clock mechanisms regulate behavioral rhythms.

  13. Meta-analysis of peripheral blood gene expression modules for COPD phenotypes.

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    Dominik Reinhold

    Full Text Available Chronic obstructive pulmonary disease (COPD occurs typically in current or former smokers, but only a minority of people with smoking history develops the disease. Besides environmental factors, genetics is an important risk factor for COPD. However, the relationship between genetics, environment and phenotypes is not well understood. Sample sizes for genome-wide expression studies based on lung tissue have been small due to the invasive nature of sample collection. Increasing evidence for the systemic nature of the disease makes blood a good alternative source to study the disease, but there have also been few large-scale blood genomic studies in COPD. Due to the complexity and heterogeneity of COPD, examining groups of interacting genes may have more relevance than identifying individual genes. Therefore, we used Weighted Gene Co-expression Network Analysis to find groups of genes (modules that are highly connected. However, module definitions may vary between individual data sets. To alleviate this problem, we used a consensus module definition based on two cohorts, COPDGene and ECLIPSE. We studied the relationship between the consensus modules and COPD phenotypes airflow obstruction and emphysema. We also used these consensus module definitions on an independent cohort (TESRA and performed a meta analysis involving all data sets. We found several modules that are associated with COPD phenotypes, are enriched in functional categories and are overrepresented for cell-type specific genes. Of the 14 consensus modules, three were strongly associated with airflow obstruction (meta p ≤ 0.0002, and two had some association with emphysema (meta p ≤ 0.06; some associations were stronger in the case-control cohorts, and others in the cases-only subcohorts. Gene Ontology terms that were overrepresented included "immune response" and "defense response." The cell types whose type-specific genes were overrepresented in modules (p < 0.05 included

  14. Molecular sub-classification of renal epithelial tumors using meta-analysis of gene expression microarrays.

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    Thomas Sanford

    Full Text Available To evaluate the accuracy of the sub-classification of renal cortical neoplasms using molecular signatures.A search of publicly available databases was performed to identify microarray datasets with multiple histologic sub-types of renal cortical neoplasms. Meta-analytic techniques were utilized to identify differentially expressed genes for each histologic subtype. The lists of genes obtained from the meta-analysis were used to create predictive signatures through the use of a pair-based method. These signatures were organized into an algorithm to sub-classify renal neoplasms. The use of these signatures according to our algorithm was validated on several independent datasets.We identified three Gene Expression Omnibus datasets that fit our criteria to develop a training set. All of the datasets in our study utilized the Affymetrix platform. The final training dataset included 149 samples represented by the four most common histologic subtypes of renal cortical neoplasms: 69 clear cell, 41 papillary, 16 chromophobe, and 23 oncocytomas. When validation of our signatures was performed on external datasets, we were able to correctly classify 68 of the 72 samples (94%. The correct classification by subtype was 19/20 (95% for clear cell, 14/14 (100% for papillary, 17/19 (89% for chromophobe, 18/19 (95% for oncocytomas.Through the use of meta-analytic techniques, we were able to create an algorithm that sub-classified renal neoplasms on a molecular level with 94% accuracy across multiple independent datasets. This algorithm may aid in selecting molecular therapies and may improve the accuracy of subtyping of renal cortical tumors.

  15. Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans

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    Benjamin Mayne

    2016-10-01

    Full Text Available The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analysed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes, followed by the heart (375 genes, kidney (224 genes, colon (218 genes and thyroid (163 genes. More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.

  16. Differentially expressed genes in the pre-eclamptic placenta: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Kleinrouweler, C. Emily; van Uitert, Miranda; Moerland, Perry D.; Ris-Stalpers, Carrie; van der Post, Joris A. M.; Afink, Gijs B.

    2013-01-01

    To systematically review the literature on human gene expression data of placental tissue in pre-eclampsia and to characterize a meta-signature of differentially expressed genes in order to identify novel putative diagnostic markers. Medline through 11 February 2011 using MeSH terms and keywords

  17. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1...... using death (P = 0.015) and recurrence (P = 0.002) as outcome. The combined mutation score is strongly associated to upregulation of several growth factor pathways....

  18. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben

    2008-01-01

    ABSTRACT: BACKGROUND: Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent stud...

  19. A whole-blood transcriptome meta-analysis identifies gene expression signatures of cigarette smoking

    NARCIS (Netherlands)

    Huan, T. (Tianxiao); R. Joehanes (Roby); C. Schurmann (Claudia); K. Schramm (Katharina); L.C. Pilling (Luke); M.J. Peters (Marjolein); R. Mägi (Reedik); D.L. Demeo (Dawn L.); G.T. O'Connor (George); L. Ferrucci (Luigi); A. Teumer (Alexander); G. Homuth (Georg); R. Biffar (Reiner); U. Völker (Uwe); C. Herder (Christian); M. Waldenberger (Melanie); A. Peters (Annette); S. Zeilinger (Sonja); A. Metspalu (Andres); A. Hofman (Albert); A.G. Uitterlinden (André); D.G. Hernandez (Dena); A. Singleton (Andrew); S. Bandinelli (Stefania); P.J. Munson (Peter); H. Lin (Honghuang); E.J. Benjamin (Emelia); T. Esko (Tõnu); H.J. Grabe (Hans Jörgen); H. Prokisch (Holger); J.B.J. van Meurs (Joyce); D. Melzer (David); D. Levy (Daniel)

    2016-01-01

    textabstractCigarette smoking is a leading modifiable cause of death worldwide. We hypothesized that cigarette smoking induces extensive transcriptomic changes that lead to target-organ damage and smoking-related diseases. We performed a metaanalysis of transcriptome-wide gene expression using whole

  20. Integrative multi-platform meta-analysis of gene expression profiles in pancreatic ductal adenocarcinoma patients for identifying novel diagnostic biomarkers.

    Science.gov (United States)

    Irigoyen, Antonio; Jimenez-Luna, Cristina; Benavides, Manuel; Caba, Octavio; Gallego, Javier; Ortuño, Francisco Manuel; Guillen-Ponce, Carmen; Rojas, Ignacio; Aranda, Enrique; Torres, Carolina; Prados, Jose

    2018-01-01

    Applying differentially expressed genes (DEGs) to identify feasible biomarkers in diseases can be a hard task when working with heterogeneous datasets. Expression data are strongly influenced by technology, sample preparation processes, and/or labeling methods. The proliferation of different microarray platforms for measuring gene expression increases the need to develop models able to compare their results, especially when different technologies can lead to signal values that vary greatly. Integrative meta-analysis can significantly improve the reliability and robustness of DEG detection. The objective of this work was to develop an integrative approach for identifying potential cancer biomarkers by integrating gene expression data from two different platforms. Pancreatic ductal adenocarcinoma (PDAC), where there is an urgent need to find new biomarkers due its late diagnosis, is an ideal candidate for testing this technology. Expression data from two different datasets, namely Affymetrix and Illumina (18 and 36 PDAC patients, respectively), as well as from 18 healthy controls, was used for this study. A meta-analysis based on an empirical Bayesian methodology (ComBat) was then proposed to integrate these datasets. DEGs were finally identified from the integrated data by using the statistical programming language R. After our integrative meta-analysis, 5 genes were commonly identified within the individual analyses of the independent datasets. Also, 28 novel genes that were not reported by the individual analyses ('gained' genes) were also discovered. Several of these gained genes have been already related to other gastroenterological tumors. The proposed integrative meta-analysis has revealed novel DEGs that may play an important role in PDAC and could be potential biomarkers for diagnosing the disease.

  1. Hematopoietically-expressed homeobox gene three widely-evaluated polymorphisms and risk for diabetes: a meta-analysis.

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    Xiaobo Li

    Full Text Available BACKGROUND: The hematopoietically-expressed homeobox (HHEX gene is identified as a promising candidate for type 2 diabetes by genome-wide association studies, triggering plenty of subsequent replications; however, the results are conflicting. We therefore conducted a meta-analysis of three widely-evaluated polymorphisms in HHEX gene and diabetes risk. METHODOLOGY/PRINCIPAL FINDINGS: A random-effects model was adopted irrespective of heterogeneity. Data and study quality were assessed in duplicate. There were 49 studies (cases/controls: 57931/74658 for rs1111875, 18 studies (18227/30366 for rs5015480 and 26 studies (25725/30579 for rs7923837, respectively. Overall analyses indicated that rs1111875-C allele (odds ratio [OR] = 1.16; 95% confidence interval [CI]: 1.13-1.2; P<0.0005, rs5015480-C allele (OR = 1.16; 95% CI: 1.06-1.26; P = 0.001 and rs7923837-G allele (OR = 1.18; 95% CI: 1.12-1.24; P<0.0005 conferred significantly increased risk for type 2 diabetes, yet accompanying moderate to strong evidence of heterogeneity. Despite vast divergence in allele distributions, subgroup analyses by ethnicity showed comparable risk estimates between Asians and Caucasians for three examined polymorphisms. Moreover, results of studies with hospital-based controls deviated greatly from that of all qualified studies, especially for rs7923837-G allele carrying a doubled risk (OR = 1.37 versus 1.18. Furthermore, when only large studies (≥ 500 case-patients were considered, risk effects were identical to the overall estimates for three examined polymorphisms. The Begg's funnel plot and Egger's test indicated low probability of publication bias. CONCLUSIONS: Our results provide clarification to the significant association of rs1111875, rs5015480 and rs7923837 in HHEX gene with type 2 diabetes.

  2. FARO server: Meta-analysis of gene expression by matching gene expression signatures to a compendium of public gene expression data

    DEFF Research Database (Denmark)

    Manijak, Mieszko P.; Nielsen, Henrik Bjørn

    2011-01-01

    circumvented by instead matching gene expression signatures to signatures of other experiments. FINDINGS: To facilitate this we present the Functional Association Response by Overlap (FARO) server, that match input signatures to a compendium of 242 gene expression signatures, extracted from more than 1700...... Arabidopsis microarray experiments. CONCLUSIONS: Hereby we present a publicly available tool for robust characterization of Arabidopsis gene expression experiments which can point to similar experimental factors in other experiments. The server is available at http://www.cbs.dtu.dk/services/faro/....

  3. Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

    DEFF Research Database (Denmark)

    de Jong, Simone; van Eijk, Kristel R; Zeegers, Dave W L H

    2012-01-01

    of the Psychiatric GWAS consortium (PGC) yielded five novel loci for schizophrenia. In this study, we aim to highlight additional schizophrenia susceptibility loci from the PGC study by combining the top association findings from the discovery stage (9394 schizophrenia cases and 12 462 controls) with expression QTLs...

  4. The Prognostic Role of Androgen Receptor in Patients with Early-Stage Breast Cancer: A Meta-analysis of Clinical and Gene Expression Data.

    Science.gov (United States)

    Bozovic-Spasojevic, Ivana; Zardavas, Dimitrios; Brohée, Sylvain; Ameye, Lieveke; Fumagalli, Debora; Ades, Felipe; de Azambuja, Evandro; Bareche, Yacine; Piccart, Martine; Paesmans, Marianne; Sotiriou, Christos

    2017-06-01

    Purpose: Androgen receptor (AR) expression has been observed in about 70% of patients with breast cancer, but its prognostic role remains uncertain. Experimental Design: To assess the prognostic role of AR expression in early-stage breast cancer, we performed a meta-analysis of studies that evaluated the impact of AR at the protein and gene expression level on disease-free survival (DFS) and/or overall survival (OS). Eligible studies were identified by systematic review of electronic databases using the MeSH-terms "breast neoplasm" and "androgen receptor" and were selected after a qualitative assessment based on the REMARK criteria. A pooled gene expression analysis of 35 publicly available microarray data sets was also performed from patients with early-stage breast cancer with available gene expression and clinical outcome data. Results: Twenty-two of 33 eligible studies for the clinical meta-analysis, including 10,004 patients, were considered as evaluable for the current study after the qualitative assessment. AR positivity defined by IHC was associated with improved DFS in all patients with breast cancer [multivariate (M) analysis, HR 0.46; 95% confidence interval (CI) 0.37-0.58, P expression analysis. High AR mRNA levels were found to confer positive prognosis overall in terms of DFS (HR 0.82; 95% CI 0.72-0.92; P = 0.0007) and OS (HR 0.84; 95% CI, 0.75-0.94; P = 0.02) only in univariate analysis. Conclusions: Our analysis, conducted among more than 17,000 women with early-stage breast cancer included in clinical and gene expression analysis, demonstrates that AR positivity is associated with favorable clinical outcome. Clin Cancer Res; 23(11); 2702-12. ©2016 AACR . ©2016 American Association for Cancer Research.

  5. Gene Expression Meta-Analysis identifies Cytokine Pathways and 5q Aberrations involved in Metastasis of ERBB2 Amplified and Basal Breast Cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Burton, Mark

    2013-01-01

    Background: Breast tumors have been described by molecular subtypes characterized by pervasively different gene expression profiles. The subtypes are associated with different clinical parameters and origin of precursor cells. However, the biological pathways and chromosomal aberrations that differ...... the subgroups impact metastasis. Results: We have scrutinized publicly available gene expression datasets and identified molecular subtypes in 1,394 breast tumors with outcome data. By analysis of chromosomal regions and pathways using “Gene set enrichment analysis” followed by a meta-analysis, we identified...... between the subgroups are less well characterized. The molecular subtypes are associated with different risk of metastatic recurrence of the disease. Nevertheless, the performance of these overall patterns to predict outcome is far from optimal, suggesting that biological mechanisms that extend beyond...

  6. Meta-analysis of Gene Expression in the Mouse Liver Reveals Biomarkers Associated with Inflammation Increased Early During Aging

    Science.gov (United States)

    Aging is associated with a predictable loss of cellular homeostasis, a decline in physiological function and an increase in various diseases. We hypothesized that similar age-related gene expression profiles would be observed in mice across independent studies. Employing a metaan...

  7. Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics

    Directory of Open Access Journals (Sweden)

    Janet M. Doolittle-Hall

    2015-11-01

    Full Text Available Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV, hepatitis B virus (HBV or Merkel cell polyomavirus (MCPyV. These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites. Features were scored in eight categories (genes, expression, open chromatin, histone modifications, methylation, protein binding, chromatin segmentation and repeats and compared to random loci. Random forest models determined loci classification and feature selection. HPV and HBV integrants were not fragile site associated. MCPyV preferred integration near sensory perception genes. Unique signatures of integration-associated predictive genomic features were detected. Importantly, repeats, actively-transcribed regions and histone modifications were common tumor viral integration signatures.

  8. When is hub gene selection better than standard meta-analysis?

    Science.gov (United States)

    Langfelder, Peter; Mischel, Paul S; Horvath, Steve

    2013-01-01

    Since hub nodes have been found to play important roles in many networks, highly connected hub genes are expected to play an important role in biology as well. However, the empirical evidence remains ambiguous. An open question is whether (or when) hub gene selection leads to more meaningful gene lists than a standard statistical analysis based on significance testing when analyzing genomic data sets (e.g., gene expression or DNA methylation data). Here we address this question for the special case when multiple genomic data sets are available. This is of great practical importance since for many research questions multiple data sets are publicly available. In this case, the data analyst can decide between a standard statistical approach (e.g., based on meta-analysis) and a co-expression network analysis approach that selects intramodular hubs in consensus modules. We assess the performance of these two types of approaches according to two criteria. The first criterion evaluates the biological insights gained and is relevant in basic research. The second criterion evaluates the validation success (reproducibility) in independent data sets and often applies in clinical diagnostic or prognostic applications. We compare meta-analysis with consensus network analysis based on weighted correlation network analysis (WGCNA) in three comprehensive and unbiased empirical studies: (1) Finding genes predictive of lung cancer survival, (2) finding methylation markers related to age, and (3) finding mouse genes related to total cholesterol. The results demonstrate that intramodular hub gene status with respect to consensus modules is more useful than a meta-analysis p-value when identifying biologically meaningful gene lists (reflecting criterion 1). However, standard meta-analysis methods perform as good as (if not better than) a consensus network approach in terms of validation success (criterion 2). The article also reports a comparison of meta-analysis techniques applied to

  9. When Is Hub Gene Selection Better than Standard Meta-Analysis?

    Science.gov (United States)

    Langfelder, Peter; Mischel, Paul S.; Horvath, Steve

    2013-01-01

    Since hub nodes have been found to play important roles in many networks, highly connected hub genes are expected to play an important role in biology as well. However, the empirical evidence remains ambiguous. An open question is whether (or when) hub gene selection leads to more meaningful gene lists than a standard statistical analysis based on significance testing when analyzing genomic data sets (e.g., gene expression or DNA methylation data). Here we address this question for the special case when multiple genomic data sets are available. This is of great practical importance since for many research questions multiple data sets are publicly available. In this case, the data analyst can decide between a standard statistical approach (e.g., based on meta-analysis) and a co-expression network analysis approach that selects intramodular hubs in consensus modules. We assess the performance of these two types of approaches according to two criteria. The first criterion evaluates the biological insights gained and is relevant in basic research. The second criterion evaluates the validation success (reproducibility) in independent data sets and often applies in clinical diagnostic or prognostic applications. We compare meta-analysis with consensus network analysis based on weighted correlation network analysis (WGCNA) in three comprehensive and unbiased empirical studies: (1) Finding genes predictive of lung cancer survival, (2) finding methylation markers related to age, and (3) finding mouse genes related to total cholesterol. The results demonstrate that intramodular hub gene status with respect to consensus modules is more useful than a meta-analysis p-value when identifying biologically meaningful gene lists (reflecting criterion 1). However, standard meta-analysis methods perform as good as (if not better than) a consensus network approach in terms of validation success (criterion 2). The article also reports a comparison of meta-analysis techniques applied to

  10. When is hub gene selection better than standard meta-analysis?

    Directory of Open Access Journals (Sweden)

    Peter Langfelder

    Full Text Available Since hub nodes have been found to play important roles in many networks, highly connected hub genes are expected to play an important role in biology as well. However, the empirical evidence remains ambiguous. An open question is whether (or when hub gene selection leads to more meaningful gene lists than a standard statistical analysis based on significance testing when analyzing genomic data sets (e.g., gene expression or DNA methylation data. Here we address this question for the special case when multiple genomic data sets are available. This is of great practical importance since for many research questions multiple data sets are publicly available. In this case, the data analyst can decide between a standard statistical approach (e.g., based on meta-analysis and a co-expression network analysis approach that selects intramodular hubs in consensus modules. We assess the performance of these two types of approaches according to two criteria. The first criterion evaluates the biological insights gained and is relevant in basic research. The second criterion evaluates the validation success (reproducibility in independent data sets and often applies in clinical diagnostic or prognostic applications. We compare meta-analysis with consensus network analysis based on weighted correlation network analysis (WGCNA in three comprehensive and unbiased empirical studies: (1 Finding genes predictive of lung cancer survival, (2 finding methylation markers related to age, and (3 finding mouse genes related to total cholesterol. The results demonstrate that intramodular hub gene status with respect to consensus modules is more useful than a meta-analysis p-value when identifying biologically meaningful gene lists (reflecting criterion 1. However, standard meta-analysis methods perform as good as (if not better than a consensus network approach in terms of validation success (criterion 2. The article also reports a comparison of meta-analysis techniques

  11. Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis.

    Science.gov (United States)

    Dong, Zhiyong; Zheng, Longzhi; Liu, Weimin; Wang, Cunchuan

    2018-01-01

    The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations. The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI. We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P =0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P =0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P =0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P =0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians.

  12. Meta-analysis methods for combining multiple expression profiles: comparisons, statistical characterization and an application guideline.

    Science.gov (United States)

    Chang, Lun-Ching; Lin, Hui-Min; Sibille, Etienne; Tseng, George C

    2013-12-21

    As high-throughput genomic technologies become accurate and affordable, an increasing number of data sets have been accumulated in the public domain and genomic information integration and meta-analysis have become routine in biomedical research. In this paper, we focus on microarray meta-analysis, where multiple microarray studies with relevant biological hypotheses are combined in order to improve candidate marker detection. Many methods have been developed and applied in the literature, but their performance and properties have only been minimally investigated. There is currently no clear conclusion or guideline as to the proper choice of a meta-analysis method given an application; the decision essentially requires both statistical and biological considerations. We performed 12 microarray meta-analysis methods for combining multiple simulated expression profiles, and such methods can be categorized for different hypothesis setting purposes: (1) HS(A): DE genes with non-zero effect sizes in all studies, (2) HS(B): DE genes with non-zero effect sizes in one or more studies and (3) HS(r): DE gene with non-zero effect in "majority" of studies. We then performed a comprehensive comparative analysis through six large-scale real applications using four quantitative statistical evaluation criteria: detection capability, biological association, stability and robustness. We elucidated hypothesis settings behind the methods and further apply multi-dimensional scaling (MDS) and an entropy measure to characterize the meta-analysis methods and data structure, respectively. The aggregated results from the simulation study categorized the 12 methods into three hypothesis settings (HS(A), HS(B), and HS(r)). Evaluation in real data and results from MDS and entropy analyses provided an insightful and practical guideline to the choice of the most suitable method in a given application. All source files for simulation and real data are available on the author's publication website.

  13. Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jonathan A Ewald

    Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

  14. Temporal profiling of cytokine-induced genes in pancreatic β-cells by meta-analysis and network inference

    DEFF Research Database (Denmark)

    Lopes, Miguel; Kutlu, Burak; Miani, Michela

    2014-01-01

    Type 1 Diabetes (T1D) is an autoimmune disease where local release of cytokines such as IL-1β and IFN-γ contributes to β-cell apoptosis. To identify relevant genes regulating this process we performed a meta-analysis of 8 datasets of β-cell gene expression after exposure to IL-1β and IFN-γ. Two...

  15. Exercise-associated DNA methylation change in skeletal muscle and the importance of imprinted genes: a bioinformatics meta-analysis.

    Science.gov (United States)

    Brown, William M

    2015-12-01

    Epigenetics is the study of processes--beyond DNA sequence alteration--producing heritable characteristics. For example, DNA methylation modifies gene expression without altering the nucleotide sequence. A well-studied DNA methylation-based phenomenon is genomic imprinting (ie, genotype-independent parent-of-origin effects). We aimed to elucidate: (1) the effect of exercise on DNA methylation and (2) the role of imprinted genes in skeletal muscle gene networks (ie, gene group functional profiling analyses). Gene ontology (ie, gene product elucidation)/meta-analysis. 26 skeletal muscle and 86 imprinted genes were subjected to g:Profiler ontology analysis. Meta-analysis assessed exercise-associated DNA methylation change. g:Profiler found four muscle gene networks with imprinted loci. Meta-analysis identified 16 articles (387 genes/1580 individuals) associated with exercise. Age, method, sample size, sex and tissue variation could elevate effect size bias. Only skeletal muscle gene networks including imprinted genes were reported. Exercise-associated effect sizes were calculated by gene. Age, method, sample size, sex and tissue variation were moderators. Six imprinted loci (RB1, MEG3, UBE3A, PLAGL1, SGCE, INS) were important for muscle gene networks, while meta-analysis uncovered five exercise-associated imprinted loci (KCNQ1, MEG3, GRB10, L3MBTL1, PLAGL1). DNA methylation decreased with exercise (60% of loci). Exercise-associated DNA methylation change was stronger among older people (ie, age accounted for 30% of the variation). Among older people, genes exhibiting DNA methylation decreases were part of a microRNA-regulated gene network functioning to suppress cancer. Imprinted genes were identified in skeletal muscle gene networks and exercise-associated DNA methylation change. Exercise-associated DNA methylation modification could rewind the 'epigenetic clock' as we age. CRD42014009800. Published by the BMJ Publishing Group Limited. For permission to use (where

  16. Identification of conserved drought-adaptive genes using a cross-species meta-analysis approach.

    Science.gov (United States)

    Shaar-Moshe, Lidor; Hübner, Sariel; Peleg, Zvi

    2015-05-03

    Drought is the major environmental stress threatening crop-plant productivity worldwide. Identification of new genes and metabolic pathways involved in plant adaptation to progressive drought stress at the reproductive stage is of great interest for agricultural research. We developed a novel Cross-Species meta-Analysis of progressive Drought stress at the reproductive stage (CSA:Drought) to identify key drought adaptive genes and mechanisms and to test their evolutionary conservation. Empirically defined filtering criteria were used to facilitate a robust integration of 17 deposited microarray experiments (148 arrays) of Arabidopsis, rice, wheat and barley. By prioritizing consistency over intensity, our approach was able to identify 225 differentially expressed genes shared across studies and taxa. Gene ontology enrichment and pathway analyses classified the shared genes into functional categories involved predominantly in metabolic processes (e.g. amino acid and carbohydrate metabolism), regulatory function (e.g. protein degradation and transcription) and response to stimulus. We further investigated drought related cis-acting elements in the shared gene promoters, and the evolutionary conservation of shared genes. The universal nature of the identified drought-adaptive genes was further validated in a fifth species, Brachypodium distachyon that was not included in the meta-analysis. qPCR analysis of 27, randomly selected, shared orthologs showed similar expression pattern as was found by the CSA:Drought.In accordance, morpho-physiological characterization of progressive drought stress, in B. distachyon, highlighted the key role of osmotic adjustment as evolutionary conserved drought-adaptive mechanism. Our CSA:Drought strategy highlights major drought-adaptive genes and metabolic pathways that were only partially, if at all, reported in the original studies included in the meta-analysis. These genes include a group of unclassified genes that could be involved

  17. Identification of cytokinin-responsive genes using microarray meta-analysis and RNA-Seq in Arabidopsis.

    Science.gov (United States)

    Bhargava, Apurva; Clabaugh, Ivory; To, Jenn P; Maxwell, Bridey B; Chiang, Yi-Hsuan; Schaller, G Eric; Loraine, Ann; Kieber, Joseph J

    2013-05-01

    Cytokinins are N(6)-substituted adenine derivatives that play diverse roles in plant growth and development. We sought to define a robust set of genes regulated by cytokinin as well as to query the response of genes not represented on microarrays. To this end, we performed a meta-analysis of microarray data from a variety of cytokinin-treated samples and used RNA-seq to examine cytokinin-regulated gene expression in Arabidopsis (Arabidopsis thaliana). Microarray meta-analysis using 13 microarray experiments combined with empirically defined filtering criteria identified a set of 226 genes differentially regulated by cytokinin, a subset of which has previously been validated by other methods. RNA-seq validated about 73% of the up-regulated genes identified by this meta-analysis. In silico promoter analysis indicated an overrepresentation of type-B Arabidopsis response regulator binding elements, consistent with the role of type-B Arabidopsis response regulators as primary mediators of cytokinin-responsive gene expression. RNA-seq analysis identified 73 cytokinin-regulated genes that were not represented on the ATH1 microarray. Representative genes were verified using quantitative reverse transcription-polymerase chain reaction and NanoString analysis. Analysis of the genes identified reveals a substantial effect of cytokinin on genes encoding proteins involved in secondary metabolism, particularly those acting in flavonoid and phenylpropanoid biosynthesis, as well as in the regulation of redox state of the cell, particularly a set of glutaredoxin genes. Novel splicing events were found in members of some gene families that are known to play a role in cytokinin signaling or metabolism. The genes identified in this analysis represent a robust set of cytokinin-responsive genes that are useful in the analysis of cytokinin function in plants.

  18. A meta-analysis of adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility

    Directory of Open Access Journals (Sweden)

    Xiuju Chen

    2016-01-01

    Full Text Available Several studies have investigated the correlation between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk. However, the results were not conclusive with each other. Therefore, to overcome this obstacle, we performed this meta-analysis to further explicate the adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility. Case-control or cohort studies focused on adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk were electronic searched in the databases of Medline, Pubmed, Cochrane library, Excerpta Medica database(EMBASE and China National Knowledge Infrastructure (CNKI. All the potentially relevant studies were included in this meta-analysis. The association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke was expressed by odds ratio with its confidence interval. Publication bias has been assessed by begg’s funnel plot. All the analyses have been performed by Revman 5.1 statistical software. Finally, a total of six studies with 1,345 cases and 1,421 controls were included in this meta-analysis. Our results demonstrated that there was a significant association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk (p<0.05. People with G single nucleotide of adiponectin gene have the increased risk of developing ischemic stroke compared to T single nucleotide.

  19. DNA repair gene polymorphisms and risk of cutaneous melanoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Mocellin, Simone; Verdi, Daunia; Nitti, Donato

    2009-10-01

    Polymorphisms of DNA repair-related genes might modulate cancer predisposition. We performed a systematic review and meta-analysis of the available evidence regarding the relationship between these polymorphisms and the risk of developing cutaneous melanoma. Relevant studies were searched using PubMed, Medline, Embase, Cancerlit, Cochrane and ISI Web of Knowledge databases. Data were gathered according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The model-free approach was adopted to perform the meta-analysis of the retrieved data. We identified 20 original reports that describe the relationship between melanoma risk and the single-nucleotide polymorphisms (SNPs) of 16 genes (cases = 4195). For seven SNPs considered in at least two studies, the findings were heterogeneous. Data were suitable for meta-analysis only in the case of the XPD/ERCC2 SNP rs13181 (cases = 2308, controls = 3698) and demonstrated that the variant C allele is associated with increased melanoma risk (odds ratio = 1.12, 95% confidence interval = 1.03-1.21, P = 0.01; population attributable risk = 9.6%). This is the first meta-analysis suggesting that XPD/ERCC2 might represent a low-penetrance melanoma susceptibility gene. Much work is still to be done before definitive conclusions can be drawn on the role of DNA repair alterations in melanomagenesis since for the other genes involved in this highly complex process, the available information is scarce or null.

  20. Meta-analysis of expression and function of neprilysin in Alzheimer's disease.

    Science.gov (United States)

    Zhang, Huifeng; Liu, Dan; Wang, Yixing; Huang, Huanhuan; Zhao, Yujia; Zhou, Hui

    2017-09-14

    Neprilysin (NEP) is one of the most important Aβ-degrading enzymes, and its expression and activity in Alzheimer's brain have been widely reported, but the results remain debatable. Thus, the meta-analysis was performed to elucidate the role of NEP in Alzheimer's disease (AD). The relevant case-control or cohort studies were retrieved according to our inclusion/exclusion criteria. Six studies with 123 controls and 141 AD cases, seven studies with 102 controls and 90 AD cases, and four studies with 93 controls and 132 AD cases were included in meta-analysis of NEP's protein, mRNA, and enzyme activity respectively. We conducted Meta regression to detect the sources of heterogeneity and further performed cumulative meta-analysis or subgroup analysis. Our meta-analysis revealed a significantly lower level of NEP mRNA (SMD=-0.44, 95%CI: -0.87, -0.00, p=0.049) in AD cases than in non-AD cases, and such pattern was not altered over time in the cumulative meta-analysis. However, the decrease of NEP protein (SMD=-0.18, 95%CI: -0.62, 0.25) and enzyme activity (SMD=-0.35, 95%CI: -1.03, 0.32) in AD cases did not pass the significance check, while the cumulative meta-analysis by average age showed the pooled effect became insignificant as adding the studies with younger subjects, which indicates that the protein expression and enzyme activity of NEP in the cortex are affected by age. Therefore, the present meta-analysis suggests the need of further investigation of roles of NEP in AD pathogenesis and treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. A Meta-Analysis of Multiple Matched Copy Number and Transcriptomics Data Sets for Inferring Gene Regulatory Relationships

    Science.gov (United States)

    Newton, Richard; Wernisch, Lorenz

    2014-01-01

    Inferring gene regulatory relationships from observational data is challenging. Manipulation and intervention is often required to unravel causal relationships unambiguously. However, gene copy number changes, as they frequently occur in cancer cells, might be considered natural manipulation experiments on gene expression. An increasing number of data sets on matched array comparative genomic hybridisation and transcriptomics experiments from a variety of cancer pathologies are becoming publicly available. Here we explore the potential of a meta-analysis of thirty such data sets. The aim of our analysis was to assess the potential of in silico inference of trans-acting gene regulatory relationships from this type of data. We found sufficient correlation signal in the data to infer gene regulatory relationships, with interesting similarities between data sets. A number of genes had highly correlated copy number and expression changes in many of the data sets and we present predicted potential trans-acted regulatory relationships for each of these genes. The study also investigates to what extent heterogeneity between cell types and between pathologies determines the number of statistically significant predictions available from a meta-analysis of experiments. PMID:25148247

  2. The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta - analysis

    NARCIS (Netherlands)

    Vaessen, Thomas Stephanus Johannes; de Jong, Lea; Schäfer, Annika Theresia; Damen, Thomas; Uittenboogaard, Aniek; Krolinski, Pauline; Nwosu, Chinyere Vicky; Pinckaers, Florentina Maria Egidius; Rotee, Iris Leah Marije; Smeets, Antonius Petrus Wilhelmus; Ermiş, Ayşegül; Kennedy, James L.; Nieman, Dorien H.; Tiwari, Arun; van Os, Jim; Drukker, Marjan

    2018-01-01

    Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl

  3. Asthma susceptible genes in Chinese population: A meta-analysis

    Directory of Open Access Journals (Sweden)

    He Chao

    2010-09-01

    Full Text Available Abstract Background Published data regarding the associations between genetic variants and asthma risk in Chinese population were inconclusive. The aim of this study was to investigate asthma susceptible genes in Chinese population. Methods The authors conducted 18 meta-analyzes for 18 polymorphisms in 13 genes from eighty-two publications. Results Seven polymorphisms were found being associated with risk of asthma, namely: A Disintegrin and Metalloprotease 33 (ADAM33 T1-C/T (odds ratio [OR] = 6.07, 95% confidence interval [CI]: 2.69-13.73, Angiotensin-Converting Enzyme (ACE D/I (OR = 3.85, 95%CI: 2.49-5.94, High-affinity IgE receptor β chain (FcεRIβ -6843G/A (OR = 1.49, 95%CI: 1.01-2.22, Interleukin 13(IL-13 -1923C/T (OR = 2.99, 95%CI: 2.12-4.24, IL-13 -2044A/G (OR = 1.49, 95%CI: 1.07-2.08, Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES -28C/G (OR = 1.64, 95%CI: 1.09-2.46, Tumor Necrosis Factor-α (TNF-α -308G/A(OR = 1.42, 95%CI: 1.09, 1.85. After subgroup analysis by age, the ACE D/I, β2-Adrenergic Receptor (β2-AR -79G/C, TNF-α -308G/A, Interleukin 4 receptor(IL-4R -1902G/A and IL-13 -1923C/T polymorphisms were found significantly associated with asthma risk in Chinese children. In addition, the ACE D/I, FcεRIβ -6843G/A, TNF-α -308G/A, IL-13 -1923C/T and IL-13 -2044A/G polymorphisms were associated with asthma risk in Chinese adults. Conclusion ADAM33, FcεRIβ, RANTES, TNF-α, ACE, β2-AR, IL-4R and IL-13 genes could be proposed as asthma susceptible genes in Chinese population. Given the limited number of studies, more data are required to validate these associations.

  4. Meta-analysis of Cancer Gene Profiling Data.

    Science.gov (United States)

    Roy, Janine; Winter, Christof; Schroeder, Michael

    2016-01-01

    The simultaneous measurement of thousands of genes gives the opportunity to personalize and improve cancer therapy. In addition, the integration of meta-data such as protein-protein interaction (PPI) information into the analyses helps in the identification and prioritization of genes from these screens. Here, we describe a computational approach that identifies genes prognostic for outcome by combining gene profiling data from any source with a network of known relationships between genes.

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

    OpenAIRE

    Zhao, Shanchao; Bao, Jiming; Song, Xianlu

    2016-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  7. Meta-Analysis of the First Facial Expression Recognition Challenge

    NARCIS (Netherlands)

    Valstar, M.F.; Mehu, M.; Jiang, Bihan; Pantic, Maja; Scherer, K.

    Automatic facial expression recognition has been an active topic in computer science for over two decades, in particular facial action coding system action unit (AU) detection and classification of a number of discrete emotion states from facial expressive imagery. Standardization and comparability

  8. Prognostic value of Notch-1 expression in hepatocellular carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Wu T

    2015-10-01

    Full Text Available Tao Wu,1 Min Jiao,1 Li Jing,1 Min-Cong Wang,1 Hai-Feng Sun,2 Qing Li,1 Yi-Yang Bai,1 Yong-Chang Wei,1 Ke-Jun Nan,1 Hui Guo1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Oncology, Shaanxi Cancer Hospital, Xi’an, People’s Republic of China Abstract: Association of Notch-1 expression with prognosis of patients with hepatocellular carcinoma (HCC remains controversial. We conducted a meta-analysis to reevaluate the association of Notch-1 expression with clinicopathological characteristics and prognosis of HCC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to look for relevant studies. The association between Notch-1 expression and clinicopathological parameters and overall survival (OS was then reassessed using the meta-analysis for odds ratio (OR or hazard ratio (HR and 95% confidence interval (CI. A total of seven studies, including 810 HCC patients, were eligible for the meta-analysis. Our data showed that high Notch-1 expression was able to predict poor OS (HR 1.50, 95% CI 1.17–1.83, P=0.0001. The pooled OR showed that high Notch-1 expression was significantly associated with tumor metastasis (OR 0.37, 95% CI 0.16–0.86, P=0.02 and tumor size >5 cm (OR 0.48, 95% CI 0.26–0.88, P=0.02. In contrast, there was no association between high Notch-1 expression and tumor differentiation, late TNM stage, tumor number, and portal vein invasion of HCC. In conclusion, Notch-1 overexpression might predict poorer survival and more aggressive behavior in patients with HCC. Keywords: hepatocellular carcinoma, Notch-1, prognosis, clinicopathological features, meta-analysis

  9. QTL global meta-analysis: are trait determining genes clustered?

    Directory of Open Access Journals (Sweden)

    Adelson David L

    2009-04-01

    Full Text Available Abstract Background A key open question in biology is if genes are physically clustered with respect to their known functions or phenotypic effects. This is of particular interest for Quantitative Trait Loci (QTL where a QTL region could contain a number of genes that contribute to the trait being measured. Results We observed a significant increase in gene density within QTL regions compared to non-QTL regions and/or the entire bovine genome. By grouping QTL from the Bovine QTL Viewer database into 8 categories of non-redundant regions, we have been able to analyze gene density and gene function distribution, based on Gene Ontology (GO with relation to their location within QTL regions, outside of QTL regions and across the entire bovine genome. We identified a number of GO terms that were significantly over represented within particular QTL categories. Furthermore, select GO terms expected to be associated with the QTL category based on common biological knowledge have also proved to be significantly over represented in QTL regions. Conclusion Our analysis provides evidence of over represented GO terms in QTL regions. This increased GO term density indicates possible clustering of gene functions within QTL regions of the bovine genome. Genes with similar functions may be grouped in specific locales and could be contributing to QTL traits. Moreover, we have identified over-represented GO terminology that from a biological standpoint, makes sense with respect to QTL category type.

  10. LncRNA expression and implication in osteosarcoma: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Wang Y

    2017-11-01

    Full Text Available Ying Wang,1,2,* Yuelong Huang,2,* Peng Xiang,3 Wei Tian2 1Department of Molecular Orthopaedics, Beijing Institute of Traumatology and Orthopaedics, 2Department of Spinal Surgery, Beijing Jishuitan Hospital, The Fourth Clinical Medical College of Peking University, 3Department of Urology, Peking University First Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Purpose: Osteosarcoma is the most prevalent primary bone tumor in children, adolescents, and older adults, typically presenting with poor survival outcomes. In recent years, ample evidence has shown that many long noncoding RNAs (lncRNAs have been aberrantly expressed in osteosarcoma, demonstrating their potential to serve as prognostic markers. In this study, we performed a meta-analysis on four lncRNAs (TUG1, UCA1, BCAR4, and HULC to systematically evaluate their prognostic value in osteosarcoma.Materials and methods: The eligible articles were systematically searched in PubMed, Web of Science, Embase, and Elsevier ScienceDirect (up to September 22, 2017, and one meta-analysis concerning the association between lncRNA expression and the overall survival (OS of osteosarcoma patients was performed. Survival outcomes were analyzed by OS. Subgroup analyses were performed.Results: A total of 1,361 patients with osteosarcoma and 12 lncRNAs from 16 articles were included in the study. Of the listed lncRNAs, the high expression of 10 lncRNAs indicated worse survival outcomes, while only two lncRNAs were shown to positively affect patients’ OS.Conclusion: This meta-analysis indicated that the abnormally expressed lncRNAs might significantly affect the survival of osteosarcoma patients. Combined use of these lncRNAs may serve as potential novel biomarkers for the indication of clinical outcomes of osteosarcoma patients as well as the selection of adjuvant chemotherapy strategies for clinical treatment of this disease. Keywords: lncRNAs, osteosarcoma

  11. Prognostic value of stromal decorin expression in patients with breast cancer: a meta-analysis.

    Science.gov (United States)

    Li, Shuang-Jiang; Chen, Da-Li; Zhang, Wen-Biao; Shen, Cheng; Che, Guo-Wei

    2015-11-01

    Numbers of studies have investigated the biological functions of decorin (DCN) in oncogenesis, tumor progression, angiogenesis and metastasis. Although many of them aim to highlight the prognostic value of stromal DCN expression in breast cancer, some controversial results still exist and a consensus has not been reached until now. Therefore, our meta-analysis aims to determine the prognostic significance of stromal DCN expression in breast cancer patients. PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literatures met out inclusion criteria. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I(2) statistic were employed to estimate the level of heterogeneity across the included studies. Sensitivity analysis was conducted to further identify the possible origins of heterogeneity. The publication bias was detected by Begg's test and Egger's test. There were three English literatures (involving 6 studies) included into our meta-analysis. On the one hand, both the summarized outcomes based on univariate analysis (HR: 0.513; 95% CI: 0.406-0.648; Panalysis (HR: 0.544; 95% CI: 0.388-0.763; Panalysis (HR: 0.504; 95% CI: 0.389-0.651; Panalysis (HR: 0.568; 95% CI: 0.400-0.806; P=0.002) also indicated that stromal DCN expression was positively associated with high disease-free survival (DFS) of breast cancer patients. No significant heterogeneity or publication bias was observed within this meta-analysis. The present evidences indicate that high stromal DCN expression can significantly predict the good prognosis in patients with breast cancer. The discoveries from our meta-analysis have better be confirmed in the updated review pooling more relevant investigations in the future.

  12. Prognostic and clinical significance of histone deacetylase 1 expression in breast cancer: A meta-analysis.

    Science.gov (United States)

    Qiao, Weiqiang; Liu, Heyang; Liu, Ruidong; Liu, Qipeng; Zhang, Ting; Guo, Wanying; Li, Peng; Deng, Miao

    2018-05-05

    There are conflicting reports about the role of histone deacetylase 1 (HDAC1) in breast cancer prognosis. Here, we conducted a meta-analysis to investigate the prognostic significance of HDAC1 in breast cancer. We searched different databases to identify studies evaluating the association between HDAC1 expression and its prognostic value in breast cancer. The pooled hazard ratios (HRs) and odds radios (ORs) with 95% confidence intervals (95% CIs) were calculated from these studies to assess specific correlation. Our meta-analysis of four databases identified 7 eligible studies with 1429 total patients. We found that HDAC1 over-expression did not correlate with disease-free survival (DFS) and overall survival (OS) in breast cancer. Subgroup analysis indicated an association between up-regulated HDAC1 expression and better OS (HR = 0.47, 95% CI: 0.23-0.97; P = 0.04) in Asian breast cancer patients. However, false-positive report probability (FPRP) analysis and trial sequential analysis (TSA) indicated that the results need further validation. Furthermore, HDAC1 over-expression was associated with positive estrogen receptor (ER) expression (OR, 3.30; 95% CI, 1.11-9.83; P = 0.03) and negative human epidermal growth factor receptor 2 (HER2) expression (OR, 1.79; 95% CI, 1.22-2.61; P = 0.003), but there were no significant differences between patients based on age, tumor size, lymph node metastasis, nuclear grade, or progesterone receptor (PR) expression. Overall, our meta-analysis demonstrated an association between increased HDAC1 expression and better OS in Asian breast cancer patients. In addition, HDAC1 over-expression correlated with positive ER and negative HER2 expression in breast cancer. However, researches in large patients' randomised controlled trials (RCTs) are needed to confirm the results. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Meta-analysis of inter-species liver co-expression networks elucidates traits associated with common human diseases.

    Directory of Open Access Journals (Sweden)

    Kai Wang

    2009-12-01

    Full Text Available Co-expression networks are routinely used to study human diseases like obesity and diabetes. Systematic comparison of these networks between species has the potential to elucidate common mechanisms that are conserved between human and rodent species, as well as those that are species-specific characterizing evolutionary plasticity. We developed a semi-parametric meta-analysis approach for combining gene-gene co-expression relationships across expression profile datasets from multiple species. The simulation results showed that the semi-parametric method is robust against noise. When applied to human, mouse, and rat liver co-expression networks, our method out-performed existing methods in identifying gene pairs with coherent biological functions. We identified a network conserved across species that highlighted cell-cell signaling, cell-adhesion and sterol biosynthesis as main biological processes represented in genome-wide association study candidate gene sets for blood lipid levels. We further developed a heterogeneity statistic to test for network differences among multiple datasets, and demonstrated that genes with species-specific interactions tend to be under positive selection throughout evolution. Finally, we identified a human-specific sub-network regulated by RXRG, which has been validated to play a different role in hyperlipidemia and Type 2 diabetes between human and mouse. Taken together, our approach represents a novel step forward in integrating gene co-expression networks from multiple large scale datasets to leverage not only common information but also differences that are dataset-specific.

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

    Directory of Open Access Journals (Sweden)

    Liang Zhou

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

  15. Meta-analysis and candidate gene mining of low-phosphorus tolerance in maize.

    Science.gov (United States)

    Zhang, Hongwei; Uddin, Mohammed Shalim; Zou, Cheng; Xie, Chuanxiao; Xu, Yunbi; Li, Wen-Xue

    2014-03-01

    Plants with tolerance to low-phosphorus (P) can grow better under low-P conditions, and understanding of genetic mechanisms of low-P tolerance can not only facilitate identifying relevant genes but also help to develop low-P tolerant cultivars. QTL meta-analysis was conducted after a comprehensive review of the reports on QTL mapping for low-P tolerance-related traits in maize. Meta-analysis produced 23 consensus QTL (cQTL), 17 of which located in similar chromosome regions to those previously reported to influence root traits. Meanwhile, candidate gene mining yielded 215 genes, 22 of which located in the cQTL regions. These 22 genes are homologous to 14 functionally characterized genes that were found to participate in plant low-P tolerance, including genes encoding miR399s, Pi transporters and purple acid phosphatases. Four cQTL loci (cQTL2-1, cQTL5-3, cQTL6-2, and cQTL10-2) may play important roles for low-P tolerance because each contains more original QTL and has better consistency across previous reports. © 2014 Institute of Botany, Chinese Academy of Sciences.

  16. Meta-analysis of expression of l(3)mbt tumor-associated germline genes supports the model that a soma-to-germline transition is a hallmark of human cancers.

    Science.gov (United States)

    Feichtinger, Julia; Larcombe, Lee; McFarlane, Ramsay J

    2014-05-15

    Evidence is starting to emerge indicating that tumorigenesis in metazoans involves a soma-to-germline transition, which may contribute to the acquisition of neoplastic characteristics. Here, we have meta-analyzed gene expression profiles of the human orthologs of Drosophila melanogaster germline genes that are ectopically expressed in l(3)mbt brain tumors using gene expression datasets derived from a large cohort of human tumors. We find these germline genes, some of which drive oncogenesis in D. melanogaster, are similarly ectopically activated in a wide range of human cancers. Some of these genes normally have expression restricted to the germline, making them of particular clinical interest. Importantly, these analyses provide additional support to the emerging model that proposes a soma-to-germline transition is a general hallmark of a wide range of human tumors. This has implications for our understanding of human oncogenesis and the development of new therapeutic and biomarker targets with clinical potential. © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  17. The Relationship between FHIT Gene Promoter Methylation and Lung Cancer Risk: 
a Meta-analysis

    Directory of Open Access Journals (Sweden)

    Yichang SUN

    2014-03-01

    Full Text Available Background and objective Tumor-suppressor gene promoter DNA methylation in tumor cells is associated with its reduced expression. FHIT (fragile histindine triad was one of the important tumor suppressor genes which was found hypermethylated in the promoter region in most of tumors. The aim of this study is to evaluate the relationship between FIHT gene promother methylation and lung cancer risk by meta-analysis. Methods By searching Pubmed, CNKI and Wanfang, the open published articles related to FHIT gene promoter methylation and lung carcinoma risk were collected. The odds ratio (OR and range of FHIT gene of cancer tissue of lung cancer patients compared with normal lung tissue, plasma and the bronchial lavage fluid were pooled by statistical software Stata 11.0. Results Eleven studies were finally included in this meta-analysis. The median methylation rate were Pmedian=40.0% (0-68.3%, Pmedian=8.7% (0-35.0%, Pmedian=33.3% (17.1%-38.3% and Pmedian=35.9% (31.1%-50.8% in cancer tissue, NLT, BALF and plasm respectively. The pooled results showed the methylation rate in tumor tissue was much higer than that of NLT OR=5.82 (95%CI: 3.74-9.06, P0.05 and plasma OR=1.41 (95%CI: 0.90-2.20, P>0.05. Conclusion Hypermethylation of FHIT gene promoter region was found more frequent in cancer tissue than that of NLT which may demonstrated association between lung cancer risk and FHIT gene promoter methylation.

  18. A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas.

    Science.gov (United States)

    Assou, Said; Le Carrour, Tanguy; Tondeur, Sylvie; Ström, Susanne; Gabelle, Audrey; Marty, Sophie; Nadal, Laure; Pantesco, Véronique; Réme, Thierry; Hugnot, Jean-Philippe; Gasca, Stéphan; Hovatta, Outi; Hamamah, Samir; Klein, Bernard; De Vos, John

    2007-04-01

    Microarray technology provides a unique opportunity to examine gene expression patterns in human embryonic stem cells (hESCs). We performed a meta-analysis of 38 original studies reporting on the transcriptome of hESCs. We determined that 1,076 genes were found to be overexpressed in hESCs by at least three studies when compared to differentiated cell types, thus composing a "consensus hESC gene list." Only one gene was reported by all studies: the homeodomain transcription factor POU5F1/OCT3/4. The list comprised other genes critical for pluripotency such as the transcription factors NANOG and SOX2, and the growth factors TDGF1/CRIPTO and Galanin. We show that CD24 and SEMA6A, two cell surface protein-coding genes from the top of the consensus hESC gene list, display a strong and specific membrane protein expression on hESCs. Moreover, CD24 labeling permits the purification by flow cytometry of hESCs cocultured on human fibroblasts. The consensus hESC gene list also included the FZD7 WNT receptor, the G protein-coupled receptor GPR19, and the HELLS helicase, which could play an important role in hESCs biology. Conversely, we identified 783 genes downregulated in hESCs and reported in at least three studies. This "consensus differentiation gene list" included the IL6ST/GP130 LIF receptor. We created an online hESC expression atlas, http://amazonia.montp.inserm.fr, to provide an easy access to this public transcriptome dataset. Expression histograms comparing hESCs to a broad collection of fetal and adult tissues can be retrieved with this web tool for more than 15,000 genes.

  19. The role of CD147 expression in prostate cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Ye, Yun; Li, Su-Liang; Wang, Yao; Yao, Yang; Wang, Juan; Ma, Yue-Yun; Hao, Xiao-Ke

    2016-01-01

    There are a number of studies which show that expression of CD147 is increased significantly in prostate cancer (PCa). However, conflicting conclusions have also been reported by other researchers lately. In order to arrive at a clear conclusion, a meta-analysis of eligible studies was conducted. We searched PubMed, MEDLINE, Cochrane Library, and the China National Knowledge Infrastructure databases to identify all the published case-control studies on the relationship between the expression of CD147 and PCa until February 2016. In the end, a total of 930 patients in eight studies were included in the meta-analysis. CD147 expression in the PCa patients increased significantly (odds ratio [OR], 4.65; 95% confidence interval [CI], 3.52-6.14; Z=10.79; PCD147 was associated with PCa among the Asian population (OR, 21.01; 95% CI, 12.88-34.28; Z=12.19; PCD147 was related to PCa, significant heterogeneity was not found between Asian studies, and the result became more significant. The positive expression of CD147 was significantly related to the clinicopathological characteristics of PCa. This suggests that CD147 plays an essential role in poor prognosis and recurrence prediction.

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

    Science.gov (United States)

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

    2012-09-01

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

  1. Clinical Significance of Resistin Expression in Osteoarthritis: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xiao-Chuan Li

    2014-01-01

    Full Text Available Background. The objective of this study was to conduct a systematic review of literature evaluating human resistin expression as a diagnostic factor in osteoarthritis development and to quantify the overall diagnostic effect. Method. Relevant studies were identified and evaluated for quality through multiple search strategies. Studies analyzing resistin expression in the development of OA were eligible for inclusion. Data from eligible studies were extracted and included into the meta-analysis using a random-effects model. Results. Four case-control studies consisting of a total of 375 OA patients and 214 controls as well as three sex-stratified analyses composed of 53 males and 104 females were incorporated into our meta-analysis. Our results revealed that resistin levels were significantly higher in male OA subjects and OA patients overall. Country-stratified analysis yielded significantly different estimates in resistin levels between male OA subjects and female OA subjects in the Canadian subgroup but not among the French and USA subgroups. Based on the resistin levels in OA cases and controls, resistin levels were heightened in OA patients in the Dutch population. Conclusion. These results support the hypothesis that high expression of resistin represents a significant and reproducible marker of poor progression in OA patients, especially in males.

  2. Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity

    DEFF Research Database (Denmark)

    Hägg, Sara; Ganna, Andrea; Van Der Laan, Sander W

    2015-01-01

    ) approach to assign variants to genes and to calculate gene-based P-values based on simulations. The VEGAS method was applied to each cohort separately before a gene-based meta-analysis was performed. In Stage 1, two known (FTO and TMEM18) and six novel (PEX2, MTFR2, SSFA2, IARS2, CEP295 and TXNDC12) loci...

  3. Brain Responses to Dynamic Facial Expressions: A Normative Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Oksana Zinchenko

    2018-06-01

    Full Text Available Identifying facial expressions is crucial for social interactions. Functional neuroimaging studies show that a set of brain areas, such as the fusiform gyrus and amygdala, become active when viewing emotional facial expressions. The majority of functional magnetic resonance imaging (fMRI studies investigating face perception typically employ static images of faces. However, studies that use dynamic facial expressions (e.g., videos are accumulating and suggest that a dynamic presentation may be more sensitive and ecologically valid for investigating faces. By using quantitative fMRI meta-analysis the present study examined concordance of brain regions associated with viewing dynamic facial expressions. We analyzed data from 216 participants that participated in 14 studies, which reported coordinates for 28 experiments. Our analysis revealed bilateral fusiform and middle temporal gyri, left amygdala, left declive of the cerebellum and the right inferior frontal gyrus. These regions are discussed in terms of their relation to models of face processing.

  4. Brain Responses to Dynamic Facial Expressions: A Normative Meta-Analysis.

    Science.gov (United States)

    Zinchenko, Oksana; Yaple, Zachary A; Arsalidou, Marie

    2018-01-01

    Identifying facial expressions is crucial for social interactions. Functional neuroimaging studies show that a set of brain areas, such as the fusiform gyrus and amygdala, become active when viewing emotional facial expressions. The majority of functional magnetic resonance imaging (fMRI) studies investigating face perception typically employ static images of faces. However, studies that use dynamic facial expressions (e.g., videos) are accumulating and suggest that a dynamic presentation may be more sensitive and ecologically valid for investigating faces. By using quantitative fMRI meta-analysis the present study examined concordance of brain regions associated with viewing dynamic facial expressions. We analyzed data from 216 participants that participated in 14 studies, which reported coordinates for 28 experiments. Our analysis revealed bilateral fusiform and middle temporal gyri, left amygdala, left declive of the cerebellum and the right inferior frontal gyrus. These regions are discussed in terms of their relation to models of face processing.

  5. Prognostic significance of p53 expression in patients with esophageal cancer: a meta-analysis

    International Nuclear Information System (INIS)

    Wang, Lianghai; Yu, Xiaodan; Li, Jing; Zhang, Zhiyu; Hou, Jun; Li, Feng

    2016-01-01

    The prognostic value of p53 protein expression in esophageal cancer has been evaluated, but the results remain inconclusive and no consensus has yet been achieved. This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in esophageal cancer. Publications that assessed the clinical or prognostic significance of p53 expression in esophageal cancer and were published before July 1, 2015 were identified by searching the PubMed and EMBASE databases. A meta-analysis was performed to clarify the association between p53 expression and the clinical outcomes. A total of 36 publications met the criteria and included 4577 cases. Analysis of these data showed that p53 expression in esophageal cancer was significantly associated with poorer 5-year survival (RR = 1.30, 95 % CI: 1.11–1.51, P = 0.0008). Subgroup analyses according to histological type, continent of the patients, and cut-off value revealed the similar results. The results also indicated that p53 expression was highly associated with advanced TNM stages (I/II vs. III/IV, OR = 0.74, 95 % CI: 0.55–0.99, P = 0.04), lymph node metastasis (OR = 0.77, 95 % CI: 0.66–0.90, P = 0.001), and distant metastasis (OR = 0.46, 95 % CI: 0.26–0.80, P = 0.006). However, p53 expression in the included studies was not significantly associated with tumor size (≤ 5 cm vs. > 5 cm, OR = 1.13, 95 % CI: 0.92–1.40, P = 0.24), tumor location (upper + middle vs. lower, OR = 0.91, 95 % CI: 0.70–1.17, P = 0.45), grade of differentiation (well + moderate vs. poor, OR = 1.10, 95 % CI: 0.90–1.34, P = 0.35), and the depth of invasion (T1/T2 vs. T3/T4, OR = 0.86, 95 % CI: 0.71–1.03, P = 0.09). This meta-analysis showed that p53 expression may be a useful biomarker for predicting poorer prognosis in patients with esophageal cancer

  6. An expression meta-analysis of predicted microRNA targets identifies a diagnostic signature for lung cancer

    Directory of Open Access Journals (Sweden)

    Liang Yu

    2008-12-01

    Full Text Available Abstract Background Patients diagnosed with lung adenocarcinoma (AD and squamous cell carcinoma (SCC, two major histologic subtypes of lung cancer, currently receive similar standard treatments, but resistance to adjuvant chemotherapy is prevalent. Identification of differentially expressed genes marking AD and SCC may prove to be of diagnostic value and help unravel molecular basis of their histogenesis and biologies, and deliver more effective and specific systemic therapy. Methods MiRNA target genes were predicted by union of miRanda, TargetScan, and PicTar, followed by screening for matched gene symbols in NCBI human sequences and Gene Ontology (GO terms using the PANTHER database that was also used for analyzing the significance of biological processes and pathways within each ontology term. Microarray data were extracted from Gene Expression Omnibus repository, and tumor subtype prediction by gene expression used Prediction Analysis of Microarrays. Results Computationally predicted target genes of three microRNAs, miR-34b/34c/449, that were detected in human lung, testis, and fallopian tubes but not in other normal tissues, were filtered by representation of GO terms and their ability to classify lung cancer subtypes, followed by a meta-analysis of microarray data to classify AD and SCC. Expression of a minimal set of 17 predicted miR-34b/34c/449 target genes derived from the developmental process GO category was identified from a training set to classify 41 AD and 17 SCC, and correctly predicted in average 87% of 354 AD and 82% of 282 SCC specimens from total 9 independent published datasets. The accuracy of prediction still remains comparable when classifying 103 AD and 79 SCC samples from another 4 published datasets that have only 14 to 16 of the 17 genes available for prediction (84% and 85% for AD and SCC, respectively. Expression of this signature in two published datasets of epithelial cells obtained at bronchoscopy from cigarette

  7. The role of CD147 expression in prostate cancer: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ye Y

    2016-08-01

    Full Text Available Yun Ye,1,2,* Su-Liang Li,2,* Yao Wang,2 Yang Yao,2 Juan Wang,1 Yue-Yun Ma,1 Xiao-Ke Hao1 1Department of Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, 2Department of Clinical Laboratory, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Background: There are a number of studies which show that expression of CD147 is increased significantly in prostate cancer (PCa. However, conflicting conclusions have also been reported by other researchers lately. In order to arrive at a clear conclusion, a meta-analysis of eligible studies was conducted.Materials and methods: We searched PubMed, MEDLINE, Cochrane Library, and the China National Knowledge Infrastructure databases to identify all the published case–control studies on the relationship between the expression of CD147 and PCa until February 2016. In the end, a total of 930 patients in eight studies were included in the meta-analysis.Results: CD147 expression in the PCa patients increased significantly (odds ratio [OR], 4.65; 95% confidence interval [CI], 3.52–6.14; Z=10.79; P<0.05, but there was obvious heterogeneity between studies (I2=92.9%, P<0.05. Subgroup analysis showed that positive expression of CD147 was associated with PCa among the Asian population (OR, 21.01; 95% CI, 12.88–34.28; Z=12.19; P<0.05. Furthermore, it was significantly related to TNM stage (OR, 0.24; 95% CI, 0.17–0.35; Z=7.74; P<0.05, Gleason score (OR, 0.41; 95% CI, 0.31–0.56; Z=5.62; P<0.05, differentiation grade (OR, 0.27; 95% CI, 0.13–0.56; Z=3.47; P<0.05, and pretreatment serum prostate-specific antigen level (OR, 0.07; 95% CI, 0.03–0.16; Z=6.47; P<0.05.Conclusion: Positive expression of CD147 was related to PCa, significant heterogeneity was not found between Asian studies, and the result became more significant. The positive expression of CD147 was significantly related to

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

    Directory of Open Access Journals (Sweden)

    Pengfei Du

    2014-01-01

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

  9. Mucin Expression in Colorectal Cancer (CRC): Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Niv, Yaron; Rokkas, Theodore

    2018-05-18

    A body of evidence has suggested that mucins play an important role in adhesion, invasion, and cancer metastasis. However, this evidence is scarce and sometimes confusing. We performed a systematic review and meta-analysis of available studies to better define the role of mucins in the behavior of colorectal cancer (CRC). Medical literature was searched through November 30, 2017, using suitable keywords. Pooled estimates, that is, odd ratios (ORs), were obtained using fixed or random-effects models, as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test and I values, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test and by the Egger regression test. A total of 2234 CRC patients were included in 12 studies, eligible for meta-analysis. There was a significant difference concerning total mucin expression between CRC patients and controls [pooled ORs (95% confidence interval)=8.156 (2.624-25.354), test for overall effect Z=3.627, PCRC, that is advanced stage versus localized disease [ORs (95% confidence interval)=2.724 (1.211-6.127), Z= 2.423, P=0.015], as opposed to MUC2 and MUC4. MUC1 is overexpressed in CRC tissue comparing with healthy mucosa, and may have a role in the neoplastic transformation and metastatic process. MUC2 has probably no role in carcinogenesis.

  10. E-selectin gene polymorphisms and essential hypertension in Asian population: an updated meta-analysis.

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    Gaojun Cai

    Full Text Available Epidemiological studies have shown that E-selectin gene polymorphisms (A561C and C1839T may be associated with essential hypertension (EH, but the results are conflicting in different ethnic populations. Thus, we performed this meta-analysis to investigate a more authentic association between E-selectin gene polymorphisms and the risk of EH.We searched the relevant studies for the present meta-analysis from the following electronic databases: PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, Wanfang Data, and China National Knowledge Infrastructure (CNKI. Odds ratios (OR with 95% confidence interval (CI were used to evaluate the strength of the association between E-selectin gene polymorphisms and EH susceptibility. The pooled ORs were performed for dominant model, allelic model and recessive model. The publication bias was examined by Begg's funnel plots and Egger's test.A total of eleven studies met the inclusion criteria. All studies came from Asians. Ten studies (12 cohorts evaluated the A561C polymorphism and EH risk, including 2,813 cases and 2,817 controls. The pooled OR was 2.280 (95%CI: 1.893-2.748, P<0.001 in dominant model, 5.284 (95%CI: 2.679-10.420, P<0.001 in recessive model and 2.359 (95%CI: 1.981-2.808, P = 0.001 in allelic model. Four studies (six cohorts evaluated C1839T polymorphism and EH risk, including 1,700 cases and 1,681 controls. The pooled OR was 0.785 (95%CI: 0.627-0.983, P = 0.035 in dominant model, 1.250 (95%CI: 0.336-4.652, P = 0.739 in recessive model and 0.805 (95%CI: 0.649-0.999, P = 0.049 in allelic model.The current meta-analysis concludes that the C allele of E-selectin A561C gene polymorphism might increase the EH risk in Asian population, whereas the T allele of E-selectin C1839T gene polymorphism might decrease the EH risk.

  11. Association between variations in the disrupted in schizophrenia 1 gene and schizophrenia: A meta-analysis.

    Science.gov (United States)

    Xu, Yiliang; Ren, Jun; Ye, Haihong

    2018-04-20

    Schizophrenia is a severe psychiatric disorder. Genetic and functional studies have strongly implicated the disrupted in schizophrenia 1 gene (DISC1) as a candidate susceptibility gene for schizophrenia. Moreover, recent association studies have indicated that several DISC1 single nucleotide polymorphisms (SNPs) are associated with schizophrenia. However, the association is hardly replicate in different ethnic group. Here, we performed a meta-analysis of the association between DISC1 SNPs and schizophrenia in which the samples were divided into subgroups according to ethnicity. Both rs3738401 and rs821616 showed not significantly association with schizophrenia in the Caucasian, Asian, Japanese or Han Chinese populations. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Three polymorphisms in interleukin-1β gene and risk for breast cancer: a meta-analysis.

    Science.gov (United States)

    Liu, Xiaoan; Wang, Zhanwei; Yu, Jinhua; Lei, Gang; Wang, Shui

    2010-12-01

    Interleukin-1β (IL-1β), which is involved in inflammatory and immunological responses, plays an important role in the development and progression of breast cancer. Three functional single nucleotide polymorphisms (SNPs) identified in IL-1β gene are thought to influence breast cancer risk. The results of the association between IL-1β polymorphisms and breast cancer remain inconsistent. Therefore, we conducted a meta-analysis of eight case-control studies with rs1143627 (T > C), rs16944 (C > T), and rs1143634 (C > T). We found that the variant CC genotype of rs1143627 was associated with a significantly increased breast cancer risk (CC vs. TT: OR = 1.37, 95% CI = 1.10-1.70, P = 0.22 for heterogeneity; the recessive model CC vs. TT/TC: OR = 1.40, 95% CI = 1.17-1.67, P = 0.49 for heterogeneity). For rs16944 (C > T) and rs1143634 (C > T), no significant associations were found in all genetic models. In conclusion, the present meta-analysis suggests that rs1143627 is associated with breast cancer risk.

  13. Association between MASP-2 gene polymorphism and risk of infection diseases: A meta-analysis.

    Science.gov (United States)

    Fu, Jie; Wang, Jingqiu; Luo, Yanping; Zhang, Lifeng; Zhang, Yuan; Dong, Xinfang; Yu, Hongjuan; Cao, Mingqiang; Ma, Xingming

    2016-11-01

    The role of MASP-2 is vital in the process of complement activation by the lectin pathway. It is generally considered that the functional activation of MASP-2 contribute to the infection disease development process. To analyze the association between MASP-2 functional gene (rs72550870) polymorphism and the infection disease risk by a meta-analysis. Relevant case-control studies were identified by searching Cochrane Library, PubMed, Emabase, DOAJ, CAB Abstracts, CSA, CINAHL, EBSCO, Scopus, Global Health, Index Copernicus, CA, China National Knowledge Infrastructure (CNKI) databases up to 10th January 2016. The data were extracted and the methodological quality of studies were evaluated. The STATA 12.0 software was used to perform statistical analysis. 9 studies were included. There was no significant association between masp-2 gene (p.D120G, rs72550870) polymorphism and the risk of infection disease under the allele model (G vs. A: OR = 0.89, 95%CI = 0.66-1.21)(P = 0.445>0.05) and the recessive model (AG + GG vs.AA: OR = 0.88, 95%CI = 0.65-1.20) (P = 0.428>0.05). This is the first comprehensive meta-analysis indicates that the MASP-2 functional gene (rs72550870) polymorphism is not associated with the infection diseases, and the key functional gene polymorphism of rs72550870 did not increase susceptibility to the infection diseases. Similarly, there were no obvious difference in subgroup analysis based on geographical areas and pathogenic microorganisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Gene expression

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

    1983-01-01

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

  15. Suppression and expression of emotion in social and interpersonal outcomes: A meta-analysis.

    Science.gov (United States)

    Chervonsky, Elizabeth; Hunt, Caroline

    2017-06-01

    Emotion expression is critical for the communication of important social information, such as emotional states and behavioral intentions. However, people tend to vary in their level of emotional expression. This meta-analysis investigated the relationships between levels of emotion expression and suppression, and social and interpersonal outcomes. PsycINFO databases, as well as reference lists were searched. Forty-three papers from a total of 3,200 papers met inclusion criteria, allowing for 105 effect sizes to be calculated. Meta-analyses revealed that greater suppression of emotion was significantly associated with poorer social wellbeing, including more negative first impressions, lower social support, lower social satisfaction and quality, and poorer romantic relationship quality. Furthermore, the expression of positive and general/nonspecific emotion was related to better social outcomes, while the expression of anger was associated with poorer social wellbeing. Expression of negative emotion generally was also associated with poorer social outcomes, although this effect size was very small and consisted of mixed results. These findings highlight the importance of considering the role that regulation of emotional expression can play in the development of social dysfunction and interpersonal problems. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

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    Ji-Ming Bao

    2014-06-01

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

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

    Science.gov (United States)

    Zhao, Shanchao; Bao, Jiming; Song, Xianlu

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  19. Association between polymorphism in STAT4 gene and risk of rheumatoid arthritis: a meta-analysis.

    Science.gov (United States)

    Tong, Guanghui; Zhang, Xiaochen; Tong, Weiwei; Liu, Yong

    2013-05-01

    Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease, affecting 1% of the population worldwide. Single nucleotide polymorphisms (SNPs) of signal transducer and activator of transcription 4 (STAT4) gene are suspected to have some relationship with the risk of RA. This meta-analysis aimed to evaluate the relationship between the polymorphism rs7574865 in STAT4 gene with RA and also examine whether the associations that have been reported in these studies differ between ethnic groups. We retrieved the relevant articles from PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) databases. The odds ratios (ORs) and their 95% confidence intervals (95% CIs) associated with the minor T allele of STAT4 rs7574865 SNP were extracted from the published studies and included in the analysis. Meta-analyses were performed on the total data set and separately for the major ethnic groups and RF and anti-CCP status. All analyses were performed using the Stata software. Twenty-three articles were included in the present analysis. Meta-analysis showed an association between the STAT4 polymorphism and RA in all subjects (OR=1.299, 95%CI=1.230-1.371, Prs7574865 T allele was significantly associated with RA in both Caucasians and Asians, in both positive and negative RF patients versus controls, also significantly in the presence of anti-CCP, both positive and negative. As for genotypes of rs7574865 polymorphism, all the results were significant, no matter in total subjects or stratified analyses by ethnic groups or by RF and anti-CCP status. Genetic polymorphism rs7574865 in STAT4 gene might be associated with RA susceptibility in total subjects, major ethnic groups and different status of anti-CCP or RF. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  20. MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

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    Wu Wei

    2011-05-01

    Full Text Available Abstract Background The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory. Methods To investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls. Results The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR = 1.25, 95% confidence interval (CI = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17. We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively. In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively. However, no association was seen between MDM2 SNP309 and tumor susceptibility

  1. A Systematic Review and Meta-Analysis of Predictors of Expressive-Language Outcomes among Late Talkers

    Science.gov (United States)

    Fisher, Evelyn L.

    2017-01-01

    Purpose: The purpose of this study was to explore the literature on predictors of outcomes among late talkers using systematic review and meta-analysis methods. We sought to answer the question: What factors predict preschool-age expressive-language outcomes among late-talking toddlers? Method: We entered carefully selected search terms into the…

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

    Directory of Open Access Journals (Sweden)

    Jun Wang

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

  3. Meta-analysis of the prognostic value of abnormally expressed lncRNAs in hepatocellular carcinoma.

    Science.gov (United States)

    Qu, Zhen; Yuan, Chun-Hui; Yin, Chang-Qing; Guan, Qing; Chen, Hao; Wang, Fu-Bing

    2016-01-01

    Many long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in hepatocellular carcinoma (HCC), and may have the potential to serve as prognostic markers. In this study, a meta-analysis was conducted to systematically evaluate the prognostic value of various lncRNAs in HCC. Eligible literatures were systematically collected from PubMed, Embase, Web of Science, and Cochrane Library (up to December 30, 2015). The main outcomes including overall survival, relapse-free survival, and disease-free survival were analyzed. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using random- or fixed-effects models. A total of 2,991 patients with HCC in People's Republic of China from 27 studies were included in the analysis. The level of lncRNAs showed a significant association with clinical outcomes. Abnormally elevated lncRNA transcription level predicted poor overall survival (HR: 1.68, 95% CI: 1.20-2.34, P=0.002; I (2)=75.5%, P=0.000) and relapse-free survival (HR: 2.08, 95% CI: 1.65-2.61, Panalysis further showed that lncRNA transcription level was significantly associated with tumor size (relative risk [RR]: 1.19, 95% CI: 1.01-1.39, P=0.035), microvascular invasion (RR: 1.44, 95% CI: 1.10-1.89, P=0.009), and portal vein tumor thrombus (RR: 1.50, 95% CI: 1.03-2.20, P=0.036). Publication bias and sensitivity analysis further confirmed the stability of our results. Our present meta-analysis indicates that abnormal lncRNA transcription level may serve as a promising indicator for prognostic evaluation of patients with HCC in People's Republic of China.

  4. Genetic variation of clock genes and cancer risk: a field synopsis and meta-analysis.

    Science.gov (United States)

    Benna, Clara; Helfrich-Förster, Charlotte; Rajendran, Senthilkumar; Monticelli, Halenya; Pilati, Pierluigi; Nitti, Donato; Mocellin, Simone

    2017-04-04

    The number of studies on the association between clock genes' polymorphisms and cancer susceptibility has increased over the last years but the results are often conflicting and no comprehensive overview and quantitative summary of the evidence in this field is available. Literature search identified 27 eligible studies comprising 96756 subjects (cases: 38231) and investigating 687 polymorphisms involving 14 clock genes. Overall, 1025 primary and subgroup meta-analyses on 366 gene variants were performed. Study distribution by tumor was as follows: breast cancer (n=15), prostate cancer (n=3), pancreatic cancer (n=2), non-Hodgkin's lymphoma (n=2), glioma (n=1), chronic lymphocytic leukemia (n=1), colorectal cancer (n=1), non-small cell lung cancer (n=1) and ovarian cancer (n=1).We identified 10 single nucleotide polymorphisms (SNPs) significantly associated with cancer risk: NPAS2 rs10165970 (mixed and breast cancer shiftworkers), rs895520 (mixed), rs17024869 (breast) and rs7581886 (breast); CLOCK rs3749474 (breast) and rs11943456 (breast); RORA rs7164773 (breast and breast cancer postmenopausal), rs10519097 (breast); RORB rs7867494 (breast cancer postmenopausal), PER3 rs1012477 (breast cancer subgroups) and assessed the level of quality evidence to be intermediate. We also identified polymorphisms with lower quality statistically significant associations (n=30). Our work supports the hypothesis that genetic variation of clock genes might affect cancer risk. These findings also highlight the need for more efforts in this research field in order to fully establish the contribution of clock gene variants to the risk of developing cancer. We conducted a systematic review and meta-analysis of the evidence on the association between clock genes' germline variants and the risk of developing cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate

  5. The SPO11-C631T gene polymorphism and male infertility risk: a meta-analysis.

    Science.gov (United States)

    Ren, Zheng-Ju; Ren, Peng-Wei; Yang, Bo; Liao, Jian; Liu, Sheng-Zhuo; Fang, Kun; Ren, Shang-Qing; Liu, Liang-Ren; Dong, Qiang

    2017-11-01

    To evaluate the association between the SPO11 gene C631T polymorphism and the risk of male infertility. We conducted a search on PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature database (CBM), VIP, and Chinese literature database (Wan Fang) on 31 March 2016. Odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of associations. A total of five studies including 542 cases and 510 controls were involved in this meta-analysis. The pooled results indicated that the SPO11 gene C631T polymorphism was significantly associated with increased risk of male infertility (TT + CT vs. CC: OR = 4.14, 95%CI = 2.48-6.89; CT vs. CC: OR = 4.34, 95%CI = 2.56-7.34; T vs. C: OR = 4.35, 95%CI = 2.58-7.34). Subgroup analysis of different countries proved the relationship between SPO11 gene C631T polymorphism and male infertility risk in Chinese, but not in Iranian peoples. In conclusion, this study suggested that SPO11 gene C631T polymorphism may contribute as a genetic factor susceptible to cause male infertility. Furthermore, more large sample and representative population-based cases and well-matched controls are needed to validate our results.

  6. Meta-analysis of microsomal epoxide hydrolase gene polymorphism and risk of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Jian-Hong Zhong

    Full Text Available BACKGROUND: Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in microsomal epoxide hydrolase (mEH. Previous work suggests an association between the Tyr113His and His139Arg mEH polymorphisms and susceptibility to hepatocellular carcinoma (HCC, but the results have been inconsistent. METHODS: PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphism and susceptibility to HCC. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated. RESULTS: Eleven studies were included in the meta-analysis, involving 1,696 HCC cases and 3,600 controls. The 113His- mEH allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.35, 95% CI = 1.04-1.75, p = 0.02, homozygote comparison (OR = 1.65, 95% CI = 1.07-2.54, p = 0.02 and a recessive genetic model (OR = 1.54, 95% CI = 1.21-1.96, p<0.001, while individuals carrying the Arg139Arg mEH genotype had no association with increased or decreased risk of HCC. CONCLUSION: The 113His- allele polymorphism in mEH may be a risk factor for hepatocarcinogenesis, while the mEH 139Arg- allele may not be a risk or protective factor. There is substantial evidence that mEH polymorphisms interact synergistically with other genes and the environment to modulate risk of HCC. Further large and well-designed studies are needed to confirm these conclusions.

  7. C-reactive protein gene polymorphisms and myocardial infarction risk: a meta-analysis and meta-regression.

    Science.gov (United States)

    Zhu, Yanbin; Liu, Tongku; He, Haitao; Sun, Yuqing; Zhuo, Fengling

    2013-12-01

    C-reactive protein (CRP), the classic acute-phase protein, plays an important role in the etiology of myocardial infarction (MI). Emerging evidence has shown that the common polymorphisms in the CRP gene may influence an individual's susceptibility to MI; but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the associations between CRP gene polymorphisms and MI risk. A literature search of PubMed, Embase, Web of Science, and China BioMedicine (CBM) databases was conducted on articles published before June 1st, 2013. Crude odds ratio (OR) with 95% confidence interval (CI) were calculated. Nine case-control studies were included with a total of 2992 MI patients and 4711 healthy controls. The meta-analysis results indicated that CRP rs3093059 (T>C) polymorphism was associated with decreased risk of MI, especially among Asian populations. However, similar associations were not observed in CRP rs1800947 (G>C) and rs2794521 (G>A) polymorphisms (all p>0.05) among both Asian and Caucasian populations. Univariate and multivariate meta-regression analyses showed that ethnicity may be a major source of heterogeneity. No publication bias was detected in this meta-analysis. In conclusion, the current meta-analysis indicates that CRP rs3093059 (T>C) polymorphism may be associated with decreased risk of MI, especially among Asian populations.

  8. Dissociation between recognition and detection advantage for facial expressions: a meta-analysis.

    Science.gov (United States)

    Nummenmaa, Lauri; Calvo, Manuel G

    2015-04-01

    Happy facial expressions are recognized faster and more accurately than other expressions in categorization tasks, whereas detection in visual search tasks is widely believed to be faster for angry than happy faces. We used meta-analytic techniques for resolving this categorization versus detection advantage discrepancy for positive versus negative facial expressions. Effect sizes were computed on the basis of the r statistic for a total of 34 recognition studies with 3,561 participants and 37 visual search studies with 2,455 participants, yielding a total of 41 effect sizes for recognition accuracy, 25 for recognition speed, and 125 for visual search speed. Random effects meta-analysis was conducted to estimate effect sizes at population level. For recognition tasks, an advantage in recognition accuracy and speed for happy expressions was found for all stimulus types. In contrast, for visual search tasks, moderator analysis revealed that a happy face detection advantage was restricted to photographic faces, whereas a clear angry face advantage was found for schematic and "smiley" faces. Robust detection advantage for nonhappy faces was observed even when stimulus emotionality was distorted by inversion or rearrangement of the facial features, suggesting that visual features primarily drive the search. We conclude that the recognition advantage for happy faces is a genuine phenomenon related to processing of facial expression category and affective valence. In contrast, detection advantages toward either happy (photographic stimuli) or nonhappy (schematic) faces is contingent on visual stimulus features rather than facial expression, and may not involve categorical or affective processing. (c) 2015 APA, all rights reserved).

  9. Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Tomasello, Gianluca; Barni, Sandro; Turati, Luca; Ghidini, Michele; Pezzica, Ezio; Passalacqua, Rodolfo; Petrelli, Fausto

    2018-02-15

    CDX2 is a homeobox gene encoding transcriptional factors for intestinal organogenesis and represents a specific marker of colorectal adenocarcinoma (CRC) differentiation. We have evaluated if CDX2 expression is associated with better overall and disease-free survival (OS and DFS) in patients with CRC. PubMed, SCOPUS, EMBASE, The Cochrane Library, and Web of Science (from inception to July 2017) were systematically reviewed for relevant studies on adult patients with CRC where OS and DFS were calculated according to CDX2 expression in uni- or multivariate analysis were included. Hazard ratio (HR) for mortality and/or disease progression was calculated. The search produced 16 studies suitable for inclusion (6291 individual patients). The meta-analysis showed a reduced risk of death for patients with CDX2-positive CRC in 14 studies (HR, 0.5; 95% confidence interval [CI], 0.38-0.66; P < .001 according to random effect model). In 6 studies where only DFS data was available, CDX2 expression led to a 52% lower risk of relapse or death (HR, 0.48; 95% CI, 0.39-0.59; P < .001 according to random effect model). The results did not change as a function of ethnicity, type of study, CDX2 detection modality, or stage. Interestingly, in stages II to III, CDX2 expression was associated with a 70% lower risk of death (HR, 0.3; 95% CI, 0.12-0.77; P = .01). CDX2 expression confirms to be a strong prognostic factor in stage II and III CRC. In this setting, along with other clinical and pathologic factors, the lack of expression of CDX2 may be considered an important variable when deciding for adjuvant chemotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Yang, Jingjing; Chen, Sai; Abecasis, Gonçalo

    2018-06-01

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

  11. Prognostic role of hypoxia-inducible factor-1 alpha expression in osteosarcoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Ren HY

    2016-03-01

    Full Text Available Hai-Yong Ren,1 Yin-Hua Zhang,1,2 Heng-Yuan Li,1 Tao Xie,1 Ling-Ling Sun,1 Ting Zhu,1 Sheng-Dong Wang,1 Zhao-Ming Ye1 1Department of Orthopaedics, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 2The First Department of Orthopaedics, Hospital of Zhejiang General Corps of Armed Police Forces, Jiaxing, People’s Republic of China Background: Hypoxia-inducible factor-1α (HIF-1α plays an important role in tumor progression and metastasis. A number of studies have investigated the association of HIF-1α with prognosis and clinicopathological characteristics of osteosarcoma but yielded inconsistent results.  Method: Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs and odds ratios (ORs with corresponding confidence intervals (CIs were calculated to assess the prognostic value of HIF-1α expression. The standard mean difference was used to analyze the continuous variable.  Results: Finally, nine studies comprising 486 patients were subjected to final analysis. Protein expression level of HIF-1α was found to be significantly related to overall survival (HR =3.0; 95% CI: 1.46–6.15, disease-free survival (HR =2.23; 95% CI: 1.26–3.92, pathologic grade (OR =21.33; 95% CI: 4.60–98.88, tumor stage (OR =10.29; 95% CI: 3.55–29.82, chemotherapy response (OR =9.68; 95% CI: 1.87–50.18, metastasis (OR =5.06; 95% CI: 2.87–8.92, and microvessel density (standard mean difference =2.83; 95% CI: 2.28–3.39.  Conclusion: This meta-analysis revealed that overexpression of HIF-1α is a predictive factor of poor outcomes for osteosarcoma. HIF-1α appeared to play an important role in prognostic evaluation and may be a potential target in antitumoral therapy. Keywords: HIF-1α, osteosarcoma, prognosis, meta-analysis

  12. Meta-analysis suggests choosy females get sexy sons more than "good genes".

    Science.gov (United States)

    Prokop, Zofia M; Michalczyk, Łukasz; Drobniak, Szymon M; Herdegen, Magdalena; Radwan, Jacek

    2012-09-01

    Female preferences for specific male phenotypes have been documented across a wide range of animal taxa, including numerous species where males contribute only gametes to offspring production. Yet, selective pressures maintaining such preferences are among the major unknowns of evolutionary biology. Theoretical studies suggest that preferences can evolve if they confer genetic benefits in terms of increased attractiveness of sons ("Fisherian" models) or overall fitness of offspring ("good genes" models). These two types of models predict, respectively, that male attractiveness is heritable and genetically correlated with fitness. In this meta-analysis, we draw general conclusions from over two decades worth of empirical studies testing these predictions (90 studies on 55 species in total). We found evidence for heritability of male attractiveness. However, attractiveness showed no association with traits directly associated with fitness (life-history traits). Interestingly, it did show a positive correlation with physiological traits, which include immunocompetence and condition. In conclusion, our results support "Fisherian" models of preference evolution, while providing equivocal evidence for "good genes." We pinpoint research directions that should stimulate progress in our understanding of the evolution of female choice. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  13. The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure: a meta-analysis involving 13,949 individuals

    DEFF Research Database (Denmark)

    Vimaleswaran, Karani Santhanakrishnan; Luan, Jian'an; Andersen, Gitte

    2008-01-01

    The protein encoded by the PPARGC1A gene is expressed at high levels in metabolically active tissues and is involved in the control of oxidative stress via reactive oxygen species detoxification. Several recent reports suggest that the PPARGC1A Gly482Ser (rs8192678) missense polymorphism may relate...... inversely with blood pressure. We used conventional meta-analysis methods to assess the association between Gly482Ser and systolic (SBP) or diastolic blood pressures (DBP) or hypertension in 13,949 individuals from 17 studies, of which 6,042 were previously unpublished observations. The studies comprised...

  14. Association between BHMT gene rs3733890 polymorphism and cancer risk: evidence from a meta-analysis

    Directory of Open Access Journals (Sweden)

    Xu Y

    2016-08-01

    Full Text Available Yue Xu,1,* Cunye Yan,2,* Zongyao Hao,1 Jun Zhou,1 Song Fan,1 Sheng Tai,1 Cheng Yang,1 Li Zhang,1 Chaozhao Liang1 1Department of Urology, The First Affiliated Hospital of Anhui Medical University and Institute of Urology, 2First School of Clinical Medicine, Anhui Medical University, Hefei, Anhui, People’s Republic of China *These authors contributed equally to this work Background and objective: The gene betaine-homocysteine methyltransferase (BHMT has drawn much attention during the past decades. An increasing number of clinical and genetic investigations have supposed that BHMT rs3733890 polymorphism might be associated with risk of breast cancer and ovarian cancer. As no consistent conclusion has been achieved, we conducted an up-to-date summary of BHMT rs3733890 polymorphism and cancer risk through a meta-analysis. Materials and methods: The articles were collected from PubMed, Google Scholar, and CNKI (Chinese databases up to December 2015. Then, the correlations were determined by reading the titles and abstracts and by further reading the full text to filter the unqualified articles. Odds ratio (OR and the corresponding 95% confidence intervals (CI were used to assess the results. Results: Among 187 articles collected in the analysis, seven studies with a total of 2,832 cases and 3,958 controls were included for evaluation of the association between BHMT rs3733890 polymorphism and susceptibility of cancer risk. The heterogeneity test showed no significant differences. Furthermore, we found that BHMT –742G>A polymorphism in case and control groups showed no statistically significant association with susceptibility in various cancer types except for uterine cervical cancer (A vs G: OR =0.641, 95% CI =0.445–0.923, P=0.017; AA+AG vs GG: OR =0.579, 95% CI =0.362–0.924, P=0.022. In addition, no statistically significant association was uncovered when stratification analyses were conducted by ethnicity and genotyping methods. Conclusion

  15. Association between interleukin 1 receptor antagonist gene 86-bp VNTR polymorphism and sepsis: a meta-analysis.

    Science.gov (United States)

    Fang, Fang; Pan, Jian; Li, Yiping; Xu, Lixiao; Su, Guanghao; Li, Gang; Wang, Jian

    2015-01-01

    Many studies have focused on the relationship between interleukin 1 receptor antagonist (IL1RN) gene 86-bp VNTR polymorphism and sepsis, but the results remain inconsistent. Thus, a meta-analysis was carried out to derive a more precise estimation of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Relevant publications were searched in several widely used databases and six eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Significant associations between IL1RN 86-bp VNTR polymorphism and sepsis risk were observed in both overall meta-analysis for L2 versus 22 (OR=0.75, 95% CI=0.59-0.94) and severe sepsis subgroup for LL+L2 versus 22 (OR=0.67, 95% CI=0.47-0.93). L stands for long alleles containing three to six repeats; 2 stands for short allele containing two repeats. However, no significant sepsis mortality variation was detected for all genetic models. According to the results of our meta-analysis, the IL1RN 86-bp VNTR polymorphism probably associates with sepsis risk but not with sepsis-related mortality. Copyright © 2014. Published by Elsevier Inc.

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

    Directory of Open Access Journals (Sweden)

    Xianli Cai

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

  17. The Effects of Expressive Writing Interventions for Patients With Cancer: A Meta-Analysis.

    Science.gov (United States)

    Oh, Pok-Ja; Kim, Soo Hyun

    2016-07-01

    To evaluate the effects of expressive writing (EW) interventions in patients with cancer.
. Electronic databases searched included both international and Korean databases through January 2015.
. Of the 20 trials that met the eligibility criteria of this review, a meta-analysis was conducted of 14 articles involving 13 randomized and 1 nonrandomized trials with 1,718 patients with cancer. EW interventions were compared with a neutral writing intervention or usual care (no writing). A significant small effect was noted on relieving cancer symptoms; however, the effects on psychological and cognitive outcomes were not significant. When subgroup analysis by control condition was performed, a significant effect on health-related quality of life was found between the EW intervention group and the usual care group. 
. EW had significant small effects only on cancer symptoms. The findings suggest that the traditional EW intervention protocol may need to be intensified to confirm its effect on patients with cancer.
. Current evidence for EW as a nursing intervention for improving physical, psychological, and cognitive outcomes among patients with cancer is promising, but not conclusive.

  18. Association between promoter polymorphisms of OPN gene and cancer risk: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Liu JW

    2015-12-01

    Full Text Available Jingwei Liu,1–2 Caiyun He,1–2 Quan Yuan,1–2 Zhenning Wang,1–2 Chengzhong Xing,1–2 Yuan Yuan1–2 1Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, 2Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, People’s Republic of China Background: Results of the association between polymorphisms of osteopontin (OPN gene promoter region and risk of cancer were inconclusive. The aim of this meta-analysis was to elucidate whether OPN promoter polymorphisms were associated with cancer risk.Methods: Electronic databases including PubMed, Web of Science, and Chinese National Knowledge Infrastructure were systematically searched. Odd ratios (ORs and their 95% confidential interval (CI were used to assess the strength of association between OPN promoter polymorphisms and cancer risks.Results: Nine studies were finally included in this meta-analysis. For OPN rs17524488 polymorphism, carriers of GG or -/G genotype were significantly associated with increased cancer risk compared with wild-type -/- carriers, respectively (GG vs -/-: OR =1.40, 95% CI =1.03–1.91, P=0.033; -/G vs -/-: OR =1.22, 95% CI =1.07–1.40, P=0.002. Additionally, G allele was significantly associated with increased cancer risk compared with (- allele (OR =1.21, 95% CI =1.04–1.40, P=0.016. However, no significant association was observed of OPN rs11730582 polymorphism and cancer risk (CC vs TT: OR =0.98, 95% CI =0.49–1.97, P=0.964; CT vs TT: OR =0.88, 95% CI =0.54–1.43, P=0.610.Conclusion: Carriers of GG or -/G genotype of OPN promoter rs17524488 (-156-/G polymorphism might be associated with increased risk of cancer compared with wild-type -/- carriers, respectively. However, no significant association was observed between OPN promoter rs11730582 (-443C/T polymorphism and risk of cancer. Keywords: OPN

  19. Human longevity and common variations in the LMNA gene: a meta-analysis

    Science.gov (United States)

    Conneely, Karen N.; Capell, Brian C.; Erdos, Michael R.; Sebastiani, Paola; Solovieff, Nadia; Swift, Amy J.; Baldwin, Clinton T.; Budagov, Temuri; Barzilai, Nir; Atzmon, Gil; Puca, Annibale A.; Perls, Thomas T.; Geesaman, Bard J.; Boehnke, Michael; Collins, Francis S.

    2012-01-01

    Summary A mutation in the LMNA gene is responsible for the most dramatic form of premature aging, Hutchinson-Gilford progeria syndrome (HGPS). Several recent studies have suggested that protein products of this gene might have a role in normal physiological cellular senescence. To explore further LMNA's possible role in normal aging, we genotyped 16 SNPs over a span of 75.4 kb of the LMNA gene on a sample of long-lived individuals (US Caucasians with age ≥95 years, N=873) and genetically matched younger controls (N=443). We tested all common non-redundant haplotypes (frequency ≥ 0.05) based on subgroups of these 16 SNPs for association with longevity. The most significant haplotype, based on 4 SNPs, remained significant after adjustment for multiple testing (OR = 1.56, P=2.5×10−5, multiple-testing-adjusted P=0.0045). To attempt to replicate these results, we genotyped 3448 subjects from four independent samples of long-lived individuals and control subjects from 1) the New England Centenarian Study (NECS) (N=738), 2) the Southern Italian Centenarian Study (SICS) (N=905), 3) France (N=1103), and 4) the Einstein Ashkenazi Longevity Study (N=702). We replicated the association with the most significant haplotype from our initial analysis in the NECS sample (OR = 1.60, P=0.0023), but not in the other three samples (P>.15). In a meta-analysis combining all five samples, the best haplotype remained significantly associated with longevity after adjustment for multiple testing in the initial and follow-up samples (OR = 1.18, P=7.5×10−4, multiple-testing-adjusted P=0.037). These results suggest that LMNA variants may play a role in human lifespan. PMID:22340368

  20. The VNTR Polymorphism of the DC-SIGNR Gene and Susceptibility to HIV-1 Infection: A Meta-Analysis

    OpenAIRE

    Li, Hui; Yu, Xiao-Min; Wang, Jia-Xin; Hong, Ze-Hui; Tang, Nelson Leung-Sang

    2012-01-01

    BACKGROUND: Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin related (DC-SIGNR) can bind to the human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein and is thus important for the host-pathogen interaction in HIV-1 infection. Studies of the association between the variable number tandem repeat (VNTR) polymorphism of the DC-SIGNR gene and HIV-1 susceptibility have produced controversial results. METHODS AND FINDINGS: We conducted a meta-analysis of th...

  1. Vitamin D receptor gene polymorphisms and the risk of rickets among Asians: a meta-analysis.

    Science.gov (United States)

    Mao, Song; Huang, Songming

    2014-03-01

    To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the risk of rickets among Asians. Eligible studies were included in our meta-analysis by searching PubMed, Embase, Cochrane and China National Knowledge Infrastructure databases according to a predefined criteria. A random effects model was used to calculate the combined ORs and its corresponding 95% CI. 16 studies were recruited for the analysis of the association between VDR BsmI (rs1544410), TaqI (rs731236), FokI (rs2228570) and ApaI (rs7975232) gene polymorphisms and the risk of rickets among Asians, most of whom were from China. B allele/BB genotype was associated with the susceptibility of rickets (p=0.017 and 0.044, respectively), and bb genotype was associated with lower risk of rickets (p=0.033). F allele/FF genotype was associated with the susceptibility of rickets (prickets (prickets (p=0.044). No significant association was observed between TaqI polymorphism the risk of rickets. A allele/aa genotype was not associated with the risk of rickets. No evidence of publication bias was observed. B allele/BB genotype at the BsmI site, F allele/FF genotype at the FokI site and AA genotype at the ApaI site may be risk factors for the onset of rickets among Asians; bb genotype at the BsmI site and ff genotype at the FokI site may be protective factors against the risk of rickets among Asians.

  2. Antibiotics and antibiotic resistance genes in global lakes: A review and meta-analysis.

    Science.gov (United States)

    Yang, Yuyi; Song, Wenjuan; Lin, Hui; Wang, Weibo; Du, Linna; Xing, Wei

    2018-04-10

    Lakes are an important source of freshwater, containing nearly 90% of the liquid surface fresh water worldwide. Long retention times in lakes mean pollutants from discharges slowly circulate around the lakes and may lead to high ecological risk for ecosystem and human health. In recent decades, antibiotics and antibiotic resistance genes (ARGs) have been regarded as emerging pollutants. The occurrence and distribution of antibiotics and ARGs in global freshwater lakes are summarized to show the pollution level of antibiotics and ARGs and to identify some of the potential risks to ecosystem and human health. Fifty-seven antibiotics were reported at least once in the studied lakes. Our meta-analysis shows that sulfamethoxazole, sulfamerazine, sulfameter, tetracycline, oxytetracycline, erythromycin, and roxithromycin were found at high concentrations in both lake water and lake sediment. There is no significant difference in the concentration of sulfonamides in lake water from China and that from other countries worldwide; however, there was a significant difference in quinolones. Erythromycin had the lowest predicted hazardous concentration for 5% of the species (HC 5 ) and the highest ecological risk in lakes. There was no significant difference in the concentration of sulfonamide resistance genes (sul1 and sul2) in lake water and river water. There is surprisingly limited research on the role of aquatic biota in propagation of ARGs in freshwater lakes. As an environment that is susceptible to cumulative build-up of pollutants, lakes provide an important environment to study the fate of antibiotics and transport of ARGs with a broad range of niches including bacterial community, aquatic plants and animals. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Polymorphisms in interleukins 17A and 17F genes and periodontitis: results from a meta-analysis.

    Science.gov (United States)

    da Silva, Felipe Rodolfo Pereira; Pessoa, Larissa Dos Santos; Vasconcelos, Any Carolina Cardoso Guimarães; de Aquino Lima, Weberson; Alves, Even Herlany Pereira; Vasconcelos, Daniel Fernando Pereira

    2017-12-01

    Polymorphisms in inflammatory genes such as interleukins 17A and 17F are associated with the risk of development of periodontitis, although the results remain contradictory. Hence, the aim of this study was perform a meta-analysis focusing on two polymorphisms (rs2275913 and rs763780) in interleukins 17A and 17F genes, respectively, in both chronic (CP) and aggressive periodontitis (AgP). A review in literature was performed in several databases for studies published before 25, September 2016. The meta-analysis was obtained through the review manager statistical software (version 5.2) with odds ratio (OR) calculation and funnel plot (P < 0.05) for heterogeneity, as well as the comprehensive meta-analysis software (version 3.3.070) for the assessment of publication bias. Seven articles with 1540 participants composed the results in which the mutant allele in the rs2275913 polymorphism did not present significant association with the risk of CP or AgP (OR 1.56, 95% CI 0.77, 3.15, P = 0.21; OR 1.12, 95% CI 0.05, 23.44, P = 0.94, respectively) nor was the mutant allele in rs763780 associated with the risk of CP (OR 1.19, 95% CI 0.80, 1.76, P = 0.39) or AgP (OR 1.07, 95% CI 0.63, 1.84, P = 0.79). No bias of publication was observed by Egger's and Begg's tests in any allelic evaluation. This meta-analysis showed a non-significant association between the polymorphisms rs2275913 and rs763780 in interleukins 17A and 17F genes and chronic and aggressive periodontitis in the allelic evaluation.

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

    Science.gov (United States)

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

    2013-08-01

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

  5. Meta-analysis of Arabidopsis KANADI1 direct target genes identifies basic growth-promoting module acting upstream of hormonal signaling pathways

    DEFF Research Database (Denmark)

    Xie, Yakun; Straub, Daniel; Eguen, Teinai Ebimienere

    2015-01-01

    An intricate network of antagonistically acting transcription factors mediates formation of a flat leaf lamina of Arabidopsis thaliana plants. In this context, members of the class III homeodomain leucine zipper (HD-ZIPIII) transcription factor family specify the adaxial domain (future upper side......) of the leaf, while antagonistically acting KANADI transcription factors determine the abaxial domain (future lower side). Here we used an mRNA-seq approach to identify genes regulated by KANADI1 (KAN1) and subsequently performed a meta-analysis approach combining our datasets with published genome......-wide datasets. Our analysis revealed that KAN1 acts upstream of several genes encoding auxin biosynthetic enzymes. When exposed to shade, we find three YUCCA genes, YUC2, YUC5 and YUC8 to be transcriptionally upregulated, which correlates with an increase in the levels of free auxin. When ectopically expressed...

  6. Prognostic value of FGFR gene amplification in patients with different types of cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jinjia Chang

    Full Text Available BACKGROUND: Fibroblast growth factor receptor (FGFR gene amplification has been reported in different types of cancer. We performed an up-to-date meta-analysis to further characterize the prognostic value of FGFR gene amplification in patients with cancer. METHODS: A search of several databases, including MEDLINE (PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure, was conducted to identify studies examining the association between FGFR gene amplification and cancer. A total of 24 studies met the inclusion criteria, and overall incidence rates, hazard risk (HR, overall survival, disease-free survival, and 95% confidence intervals (CIs were calculated employing fixed- or random-effects models depending on the heterogeneity of the included studies. RESULTS: In the meta-analysis of 24 studies, the prevalence of FGFR gene amplification was FGFR1: 0.11 (95% CI: 0.08-0.13 and FGFR2: 0.04 (95% CI: 0.02-0.06. Overall survival was significantly worse among patients with FGFR gene amplification: FGFR1 [HR 1.57 (95% CI: 1.23-1.99; p = 0.0002] and FGFR2 [HR 2.27 (95% CI: 1.73-3.00; p<0.00001]. CONCLUSIONS: Current evidence supports the conclusion that the outcomes of patients with FGFR gene amplified cancers is worse than for those with non-FGFR gene amplified cancers.

  7. The role of the Cys23Ser (rs6318) polymorphism of the HTR2C gene in suicidal behavior: systematic review and meta-analysis.

    Science.gov (United States)

    González-Castro, Thelma B; Hernandez-Diaz, Yazmín; Juárez-Rojop, Isela E; López-Narváez, Lilia; Tovilla-Zárate, Carlos A; Rodriguez-Perez, José M; Sánchez-de la Cruz, Juan P

    2017-12-01

    The polymorphisms of the serotonin receptor 2C (HTR2C) gene have been proposed to influence suicidal behavior. The aim of our study was to explore the role of the HTR2C gene variant Cys23Ser (rs6318) in the pathogenesis of suicidal behavior through a systematic review and meta-analysis. The search was performed using EBSCO and PubMed databases. To be included in the analysis, the studies had to evaluate suicidal behavior (attempted, ideation, or completed suicide). The results of the meta-analysis were expressed as odds ratios (ORs). Because HTR2C lies on chromosome X, pooled ORs were calculated, respectively, for each of the models used, namely: allelic, homozygous, dominant, and recessive for the female group and allelic for the male group. The meta-analysis comprised 3867 individuals, including 1668 cases and 2199 controls. The HTR2C Cys23Ser (rs6318) polymorphism did not show a significant association with suicidal behavior either in women (OR: 0.75; 95% confidence interval: 0.55-1.00) or in men (OR: 0.89; 95% confidence interval: 0.64-1.23). Similarly, nonsignificant associations were observed for all of the genetic models used in any of the populations/subgroups studied. Our findings suggest that the rs6318 (Cys23Ser) polymorphism is not associated with suicidal behavior. However, because of the study limitations, we suggest more researches should be performed, increasing the sample sizes and statistical power, to determine the association between the rs6318 variant and suicidal behavior.

  8. Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA Splicing Regulatory Genes

    Directory of Open Access Journals (Sweden)

    Elvezia Maria Paraboschi

    2015-09-01

    Full Text Available Abnormalities in RNA metabolism and alternative splicing (AS are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls, followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p = 0.0015 by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes.

  9. Note of the methodological flaws in the paper entitled "Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis".

    Science.gov (United States)

    Wang, Ting-Ting; Li, Jin-Mei; Zhou, Dong

    2016-01-01

    With great interest, we read the paper "Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis" (by Chen PQ et al.) [1], which has reached important conclusions about the relationship between polymorphisms in interleukin (IL)-4/IL-13 pathway genes and glioma risk. Through quantitative analysis, the meta-analysis found no association between IL-4/IL-13 pathway genetic polymorphisms and glioma risk (Chen et al. in Tumor Biol 36:121-127, 2015). The meta-analysis is the most comprehensive study of polymorphisms in the IL-4/IL-13 pathway and glioma risk. Nevertheless, some deficiencies still exist in this meta-analysis that we would like to raise.

  10. Systematic review and meta-analysis: the relationship between the Helicobacter pylori dupA gene and clinical outcomes

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    Shiota Seiji

    2010-10-01

    Full Text Available Abstract Background In 2005, the first disease-specific Helicobacter pylori virulence factor that induced duodenal ulcer and had a suppressive action on gastric cancer has been identified, and was named duodenal ulcer promoting gene (dupA. However, the importance of the dupA gene on clinical outcomes is conflicting in subsequent studies. The aim of this study was to estimate the magnitude of the risk for clinical outcomes associated with dupA gene. Methods A meta-analysis of case-control studies which provided raw data on the infection rates with the dupA-positive H. pylori detected by polymerase chain reaction was performed. Results Seventeen studies with a total of 2,466 patients were identified in the search. Infection with the dupA-positive H. pylori increased the risk for duodenal ulcer by 1.41-fold (95% confidence interval [CI], 1.12-1.76 overall. Subgroup analysis showed that the summary odds ratio (OR was 1.57 (95% CI, 1.19-2.06 in Asian countries and 1.09 (95% CI, 0.73-1.62 in Western countries. There was no association between the presence of the dupA gene and gastric cancer and gastric ulcer. Publication bias did not exist. Conclusion Our meta-analysis confirmed the importance of the presence of the dupA gene for duodenal ulcer, especially in Asian countries.

  11. Systematic review and meta-analysis: the relationship between the Helicobacter pylori dupA gene and clinical outcomes.

    Science.gov (United States)

    Shiota, Seiji; Matsunari, Osamu; Watada, Masahide; Hanada, Katsuhiro; Yamaoka, Yoshio

    2010-10-31

    In 2005, the first disease-specific Helicobacter pylori virulence factor that induced duodenal ulcer and had a suppressive action on gastric cancer has been identified, and was named duodenal ulcer promoting gene (dupA). However, the importance of the dupA gene on clinical outcomes is conflicting in subsequent studies. The aim of this study was to estimate the magnitude of the risk for clinical outcomes associated with dupA gene. A meta-analysis of case-control studies which provided raw data on the infection rates with the dupA-positive H. pylori detected by polymerase chain reaction was performed. Seventeen studies with a total of 2,466 patients were identified in the search. Infection with the dupA-positive H. pylori increased the risk for duodenal ulcer by 1.41-fold (95% confidence interval [CI], 1.12-1.76) overall. Subgroup analysis showed that the summary odds ratio (OR) was 1.57 (95% CI, 1.19-2.06) in Asian countries and 1.09 (95% CI, 0.73-1.62) in Western countries. There was no association between the presence of the dupA gene and gastric cancer and gastric ulcer. Publication bias did not exist. Our meta-analysis confirmed the importance of the presence of the dupA gene for duodenal ulcer, especially in Asian countries.

  12. Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review.

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    Kim, Bum Jun; Kim, Jung Han; Kim, Hyeong Su; Zang, Dae Young

    2017-02-21

    The von Hippel-Lindau (VHL) gene is often inactivated in sporadic renal cell carcinoma (RCC) by mutation or promoter hypermethylation. The prognostic or predictive value of VHL gene alteration is not well established. We conducted this meta-analysis to evaluate the association between the VHL alteration and clinical outcomes in patients with RCC. We searched PUBMED, MEDLINE and EMBASE for articles including following terms in their titles, abstracts, or keywords: 'kidney or renal', 'carcinoma or cancer or neoplasm or malignancy', 'von Hippel-Lindau or VHL', 'alteration or mutation or methylation', and 'prognostic or predictive'. There were six studies fulfilling inclusion criteria and a total of 633 patients with clear cell RCC were included in the study: 244 patients who received anti-vascular endothelial growth factor (VEGF) therapy in the predictive value analysis and 419 in the prognostic value analysis. Out of 663 patients, 410 (61.8%) had VHL alteration. The meta-analysis showed no association between the VHL gene alteration and overall response rate (relative risk = 1.47 [95% CI, 0.81-2.67], P = 0.20) or progression free survival (hazard ratio = 1.02 [95% CI, 0.72-1.44], P = 0.91) in patients with RCC who received VEGF-targeted therapy. There was also no correlation between the VHL alteration and overall survival (HR = 0.80 [95% CI, 0.56-1.14], P = 0.21). In conclusion, this meta-analysis indicates that VHL gene alteration has no prognostic or predictive value in patients with clear cell RCC.

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

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    Kai Zhang

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

  14. Recent adaptive events in human brain revealed by meta-analysis of positively selected genes.

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    Yue Huang

    Full Text Available BACKGROUND AND OBJECTIVES: Analysis of positively-selected genes can help us understand how human evolved, especially the evolution of highly developed cognitive functions. However, previous works have reached conflicting conclusions regarding whether human neuronal genes are over-represented among genes under positive selection. METHODS AND RESULTS: We divided positively-selected genes into four groups according to the identification approaches, compiling a comprehensive list from 27 previous studies. We showed that genes that are highly expressed in the central nervous system are enriched in recent positive selection events in human history identified by intra-species genomic scan, especially in brain regions related to cognitive functions. This pattern holds when different datasets, parameters and analysis pipelines were used. Functional category enrichment analysis supported these findings, showing that synapse-related functions are enriched in genes under recent positive selection. In contrast, immune-related functions, for instance, are enriched in genes under ancient positive selection revealed by inter-species coding region comparison. We further demonstrated that most of these patterns still hold even after controlling for genomic characteristics that might bias genome-wide identification of positively-selected genes including gene length, gene density, GC composition, and intensity of negative selection. CONCLUSION: Our rigorous analysis resolved previous conflicting conclusions and revealed recent adaptation of human brain functions.

  15. A meta-analysis of xeroderma pigmentosum gene D Ls751Gln polymorphism and susceptibility to hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Yu; Zhao, Yingren; Zhang, Aiyun; Ma, Juan; Wang, Zhenzhen; Zhang, Xu

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of most common malignant tumors worldwide, but with unclear mechanisms. Xeroderma pigmentosum gene D (XPD) is one important DNA damage repair gene and can be involved in protein mutation. Currently little has been known about XPD polymorphism and HCC susceptibility in Chinese people. This study used a meta-analysis approach to comprehensively investigate the correlation between XPD polymorphism and HCC susceptibility in Chinese population, based on previously published literatures. A computer retrieval system was used to collect all case-control studies about XPD Lys751Gln polymorphism and HCC susceptibility. Data in literatures were extracted for meta-analysis. After the primary screening, four independent studies, which were published in 3 English articles and one Chinese article, were recruited in this study. There were 1,717 samples included in all studies. Using Gln/Gln + Lys/Gln, Lys/Lys + Lys/Gln and Lys allels as the reference, HCC disease alleles including Lys/Lys, Gln/Gln and Gln had OR values (95% CI, I(2)) of 1.007 (0.657~4.672, 91%), 3.516 (0.220~20.661, 48%) and 3.225 (0.278~12.326, 84%), respectively. The polymorphism of XPD751 loci is closely correlated with primary HCC. Lys751Gln polymorphism of XPD gene can be used as one susceptibility factor for HCC.

  16. Associations between dopamine D2 receptor gene polymorphisms and schizophrenia risk: a PRISMA compliant meta-analysis

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    He HR

    2016-12-01

    Full Text Available Hairong He,1 Huanhuan Wu,1,2 Lihong Yang,1 Fan Gao,1 Yajuan Fan,3 Junqin Feng,3 Xiancang Ma1,3 1Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, 2College of Pharmacy, Xi’an Medical University, 3Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China Objective: To determine the relationships between dopamine D2 receptor gene polymorphisms and the risk of schizophrenia using meta-analysis.Method: The PubMed, Embase, and China National Knowledge Infrastructure databases were searched to identify relevant literature published up to February 2016. The allele contrast model was used. STATA software was used for statistical analysis, with odds ratios (ORs and 95% confidence intervals (CIs calculated to evaluate the associations between dopamine D2 receptor gene polymorphisms and the risk of schizophrenia. Meta-regression and publication bias, trim-and-fill, subgroup, sensitivity, cumulative, and fail-safe number analyses were also performed.Results: This meta-analysis included 81 studies. The rs1801028 and rs1799732 were associated with schizophrenia risk among Asians (P=0.04, OR =1.25, 95% CI =1.01–1.55; P<0.01, OR =0.76, 95% CI =0.63–0.92, respectively, while the rs6277 was associated with schizophrenia risk in Caucasians (P<0.01, OR=0.72, 95% CI =0.66–0.79. The rs1800497 was also associated with schizophrenia risk in population-based controls (P<0.01, OR =0.84, 95% CI =0.72–0.97. The rs6275, rs1079597, and rs1800498 were not associated with schizophrenia risk. In addition, meta-regression indicated that the controls may be sources of heterogeneity for the rs1801028 single-nucleotide polymorphism (SNP, while ethnicity may be sources of heterogeneity for the rs6277 SNP. Publication bias was significant for the rs1801028 SNP, and this result changed after the publication bias was adjusted using the trim-and-fill method

  17. Prognostic and clinicopathological significance of serum interleukin-6 expression in colorectal cancer: a systematic review and meta-analysis

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    Wang Z

    2015-12-01

    Full Text Available Zhen Wang,1 Pin Wu,1,2 Dang Wu,1 Zhigang Zhang,3 Guoming Hu,1 Shuai Zhao,1 Yucheng Lai,1 Jian Huang1,41Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Key Laboratory of Molecular Biology in Medical Sciences, China National Ministry of Education, 2Department of Thoracic Surgery, 3Department of Gynecology, 4Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of ChinaPurpose: Interleukin-6 (IL-6 plays an important role in human colorectal cancer (CRC development. However, the exact clinical and prognostic significance of IL-6 in CRC is still unclear. Here, we conducted this meta-analysis to explore this issue in detail.Methods: A meta-analysis was performed to clarify the association between serum IL-6 expression and clinical outcomes in articles published up to June 2015. Weighted mean difference (WMD and its corresponding 95% confidence interval (CI were used to assess the association between serum IL-6 expression and the clinicopathological characteristics of CRC. Hazard ratio (HR with 95% CI was used to quantify the predictive value of IL-6 on CRC prognosis.Results: Fourteen studies comprising 1,245 patients were included. Analysis of these data showed that serum IL-6 expression was highly correlated with poor 5-year overall survival (OS rate (HR =0.43, 95% CI: 0.31–0.59, P=0.755. Simultaneously, we also found that serum IL-6 expression was associated with certain clinical parameters of CRC, such as tumor invasion (T category: T0–T2, T3–T4 (WMD =3.15, 95% CI: 1.92–4.39, P=0.816, distant metastasis (M category: M0, M1 (WMD =4.69, 95% CI: 3.33–6.06, P=0.377, and tumor stage (I–II, III–IV (WMD =2.65, 95% CI: 1.09–4.21, P=0.066.Conclusion: A high serum IL-6 expression is associated with adverse OS in CRC. The IL-6 expression can be an important supplement in establishing prognostic score

  18. Impact of S100A4 Expression on Clinicopathological Characteristics and Prognosis in Pancreatic Cancer: A Meta-Analysis

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    Shanshan Huang

    2016-01-01

    Full Text Available Background. The small Ca2+-binding protein S100A4 is identified as a metastasis-associated or metastasis-inducing protein in various types of cancer. The goal of this meta-analysis was to evaluate the relationship between S100A4 expression and clinicopathological characteristics and prognosis of patients with pancreatic cancer. Methods. A comprehensive literature search was carried out in the electronic databases PubMed and Chinese CNKI. Only the studies reporting the correlation between S100A4 expression and clinicopathological characteristics or overall survival (OS of patients with pancreatic cancer are enrolled. Extracted data was analyzed using the RevMan 5.3 software to calculate the pooled relative risks (95% confidence interval, CI for statistical analyses. Results. Seven studies including a total of 474 patients were enrolled into this meta-analysis. Negative expression of S100A4 was significantly associated with higher 3-year OS rate (RR = 3.92, 95% CI = 2.24–6.87, P<0.0001, compared to S100A4-positive cases. Moreover, negative expression of S100A4 was also related to N0 stage for lymph node metastasis (RR = 2.15, 95% CI = 1.60–2.88, P<0.0001. However, S100A4 expression was not significantly correlated with histological types and distant metastasis status. Conclusion. S100A4 expression represents a potential marker for lymph node metastasis of pancreatic cancer and a potential unfavorable factor for prognosis of patients with this disease.

  19. ESR1 Gene Polymorphisms and Prostate Cancer Risk: A HuGE Review and Meta-Analysis.

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    Yu-Mei Wang

    Full Text Available Many published data on the association between single nucleotide polymorphisms (SNPs in the ESR1 gene and prostate cancer susceptibility are inconclusive. The aim of this Human Genome Epidemiology (HuGE review and meta-analysis is to derive a more precise estimation of this relationship.A literature search of PubMed, Embase, Web of Science and Chinese Biomedical (CBM databases was conducted from their inception through July 1st, 2012. Crude odds ratios (ORs with 95% confidence intervals (CIs were calculated to assess the strength of association.Twelve case-control studies were included with a total 2,165 prostate cancer cases and 3,361 healthy controls. When all the eligible studies were pooled into the meta-analysis, ESR1 PvuII (C>T and XbaI (A>G polymorphisms showed no association with the risk of prostate cancer. However, in the stratified analyses based on ethnicity and country, the results indicated that ESR1 PvuII (C>T polymorphism was significantly associated with increased risk of prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G polymorphism may significantly increase the risk of prostate cancer among American population. Furthermore, we also performed a pooled analysis for all eligible case-control studies to explore the role of codon 10 (T>C, codon 325 (C>G, codon 594 (G>A and +261G>C polymorphisms in prostate cancer risk. Nevertheless, no significant associations between these polymorphisms and the risk of prostate cancer were observed.Results from the current meta-analysis indicate that ESR1 PvuII (C>T polymorphism may be a risk factor for prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G polymorphism may increase the risk of prostate cancer among American population.

  20. Quantitative Trait Locus (QTL meta-analysis and comparative genomics for candidate gene prediction in perennial ryegrass (Lolium perenne L.

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    Shinozuka Hiroshi

    2012-11-01

    Full Text Available Abstract Background In crop species, QTL analysis is commonly used for identification of factors contributing to variation of agronomically important traits. As an important pasture species, a large number of QTLs have been reported for perennial ryegrass based on analysis of biparental mapping populations. Further characterisation of those QTLs is, however, essential for utilisation in varietal improvement programs. Results A bibliographic survey of perennial ryegrass trait-dissection studies identified a total of 560 QTLs from previously published papers, of which 189, 270 and 101 were classified as morphology-, physiology- and resistance/tolerance-related loci, respectively. The collected dataset permitted a subsequent meta-QTL study and implementation of a cross-species candidate gene identification approach. A meta-QTL analysis based on use of the BioMercator software was performed to identify two consensus regions for pathogen resistance traits. Genes that are candidates for causal polymorphism underpinning perennial ryegrass QTLs were identified through in silico comparative mapping using rice databases, and 7 genes were assigned to the p150/112 reference map. Markers linked to the LpDGL1, LpPh1 and LpPIPK1 genes were located close to plant size, leaf extension time and heading date-related QTLs, respectively, suggesting that these genes may be functionally associated with important agronomic traits in perennial ryegrass. Conclusions Functional markers are valuable for QTL meta-analysis and comparative genomics. Enrichment of such genetic markers may permit further detailed characterisation of QTLs. The outcomes of QTL meta-analysis and comparative genomics studies may be useful for accelerated development of novel perennial ryegrass cultivars with desirable traits.

  1. Meta-analysis of microsomal epoxide hydrolase gene polymorphism and risk of hepatocellular carcinoma.

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    Zhong, Jian-Hong; Xiang, Bang-De; Ma, Liang; You, Xue-Mei; Li, Le-Qun; Xie, Gui-Sheng

    2013-01-01

    Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in microsomal epoxide hydrolase (mEH). Previous work suggests an association between the Tyr113His and His139Arg mEH polymorphisms and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent. PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphism and susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Eleven studies were included in the meta-analysis, involving 1,696 HCC cases and 3,600 controls. The 113His- mEH allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.35, 95% CI = 1.04-1.75, p = 0.02), homozygote comparison (OR = 1.65, 95% CI = 1.07-2.54, p = 0.02) and a recessive genetic model (OR = 1.54, 95% CI = 1.21-1.96, penvironment to modulate risk of HCC. Further large and well-designed studies are needed to confirm these conclusions.

  2. Meta-analysis of studies using suppression subtractive hybridization and microarrays to investigate the effects of environmental stress on gene transcription in oysters.

    Science.gov (United States)

    Anderson, Kelli; Taylor, Daisy A; Thompson, Emma L; Melwani, Aroon R; Nair, Sham V; Raftos, David A

    2015-01-01

    Many microarray and suppression subtractive hybridization (SSH) studies have analyzed the effects of environmental stress on gene transcription in marine species. However, there have been no unifying analyses of these data to identify common stress response pathways. To address this shortfall, we conducted a meta-analysis of 14 studies that investigated the effects of different environmental stressors on gene expression in oysters. The stressors tested included chemical contamination, hypoxia and infection, as well as extremes of temperature, pH and turbidity. We found that the expression of over 400 genes in a range of oyster species changed significantly after exposure to environmental stress. A repeating pattern was evident in these transcriptional responses, regardless of the type of stress applied. Many of the genes that responded to environmental stress encoded proteins involved in translation and protein processing (including molecular chaperones), the mitochondrial electron transport chain, anti-oxidant activity and the cytoskeleton. In light of these findings, we put forward a consensus model of sub-cellular stress responses in oysters.

  3. Common variant in the glucokinase regulatory gene rs780094 and risk of nonalcoholic fatty liver disease: a meta-analysis.

    Science.gov (United States)

    Zain, Shamsul Mohd; Mohamed, Zahurin; Mohamed, Rosmawati

    2015-01-01

    Although studies have suggested that rs780094, a common variant in the glucokinase regulatory (GCKR) gene to be associated with type 2 diabetes, obesity, and their related traits, the genetic basis of the association between GCKR rs780094 and nonalcoholic fatty liver disease (NAFLD) is still being examined. This meta-analysis was performed to evaluate the effect strength caused by GCKR rs780094 on NAFLD. We searched Medline, PubMed, Scopus, and Embase for relevant articles published up to April 2014. Data were extracted, and summary estimates of the association between GCKR rs780094 and NAFLD were examined. Heterogeneity and publication bias were also examined. This meta-analysis incorporated a total of 2091 NAFLD cases and 3003 controls from five studies. Overall, the pooled result indicated that the GCKR rs780094 was significantly associated with increased risk of NAFLD (additive: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.14-1.36, P risk of NAFLD. Similar effect size was demonstrated in both Asian and non-Asian populations. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  4. Height outcome of the recombinant human growth hormone treatment in patients with SHOX gene haploinsufficiency: a meta-analysis.

    Science.gov (United States)

    Massart, Francesco; Bizzi, Martina; Baggiani, Angelo; Miccoli, Mario

    2013-04-01

    Patients with mutations or deletions of the SHOX gene present variable growth impairment, with or without mesomelic skeletal dysplasia. If untreated, short patients with SHOX haplodeficiency (SHOXD) remain short into adulthood. Although recombinant human growth hormone (rhGH) treatment improves short-term linear growth, there are episodic data on the final height of treated SHOXD subjects. After a thorough search of the published literature for pertinent studies, we undertook a meta-analysis evaluation of the efficacy and safety of rhGH treatment in SHOXD patients. In SHOXD patients, administration of rhGH progressively improved the height deficit from baseline to 24 months, although the major catch-up growth was detected after 12 months. The rhGH-induced growth appeared constant until final height. Our meta-analysis suggested rhGH therapy improves height outcome of SHOXD patients, though future studies using carefully titrated rhGH protocols are needed. Original submitted 29 October 2012; Revision submitted 22 February 2013.

  5. Association between alcohol dehydrogenase 1C gene *1/*2 polymorphism and pancreatitis risk: a meta-analysis.

    Science.gov (United States)

    Fang, F; Pan, J; Su, G H; Xu, L X; Li, G; Li, Z H; Zhao, H; Wang, J

    2015-11-30

    Numerous studies have focused on the relationship be-tween alcohol dehydrogenase 1C gene (ADH1C) *1/*2 polymorphism (Ile350Val, rs698, also known as ADH1C *1/*2) and pancreatitis risk, but the results have been inconsistent. Thus, we conducted a meta-anal-ysis to more precisely estimate this association. Relevant publications were searched in several widely used databases and 9 eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Significant associations between ADH1C *1/*2 poly-morphism and pancreatitis risk were observed in both overall meta-analysis for 12 vs 22 (OR = 1.53, 95%CI = 1.12-2.10) and 11 + 12 vs 22 (OR = 1.44, 95%CI = 1.07-1.95), and the chronic alcoholic pancre-atitis subgroup for 12 vs 22 (OR = 1.64, 95%CI = 1.17-2.29) and 11 + 12 vs 22 (OR = 1.53, 95%CI = 1.11-2.11). Significant pancreatitis risk variation was also detected in Caucasians for 11 + 12 vs 22 (OR = 1.45, 95%CI = 1.07-1.98). In conclusion, the ADH1C *1/*2 polymorphism is likely associated with pancreatitis risk, particularly chronic alcoholic pancreatitis risk, with the *1 allele functioning as a risk factor.

  6. The Association between Abnormal Long Noncoding RNA MALAT-1 Expression and Cancer Lymph Node Metastasis: A Meta-Analysis

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    Jun Wang

    2016-01-01

    Full Text Available Previous studies have investigated that the expression levels of MALAT-1 were higher in cancerous tissues than matched histologically normal tissues. And, to some extent, overexpression of MALAT-1 was inclined to lymph node metastasis. This meta-analysis collected all relevant articles and explored the association between MALAT-1 expression levels and lymph node metastasis. We searched PubMed, EmBase, Web of Science, Cochrane Library, and OVID to address the level of MALAT-1 expression in cancer cases and noncancerous controls (accessed February 2015. And 8 studies comprising 696 multiple cancer patients were included to assess this association. The odds ratio (OR and its corresponding 95% confidence interval (CI were calculated to assess the strength of the association using Stata 12.0 version software. The results revealed there was a significant difference in the incidence of lymph node metastasis between high MALAT-1 expression group and low MALAT-1 expression group (OR = 1.94, 95% CI 1.15–3.28, P=0.013 random-effects model. Subgroup analysis indicated that MALAT-1 high expression had an unfavorable impact on lymph node metastasis in Chinese patients (OR = 1.87, 95% CI 1.01–2.46. This study demonstrated that the incidence of lymph node metastasis in patients detected with high MALAT-1 expression was higher than that in patients with low MALAT-1 expression in China.

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

    Science.gov (United States)

    2014-01-01

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

  8. A meta-analysis based method for prioritizing candidate genes involved in a pre-specific function

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    Jingjing Zhai

    2016-12-01

    Full Text Available The identification of genes associated with a given biological function in plants remains a challenge, although network-based gene prioritization algorithms have been developed for Arabidopsis thaliana and many non-model plant species. Nevertheless, these network-based gene prioritization algorithms have encountered several problems; one in particular is that of unsatisfactory prediction accuracy due to limited network coverage, varying link quality, and/or uncertain network connectivity. Thus a model that integrates complementary biological data may be expected to increase the prediction accuracy of gene prioritization. Towards this goal, we developed a novel gene prioritization method named RafSee, to rank candidate genes using a random forest algorithm that integrates sequence, evolutionary, and epigenetic features of plants. Subsequently, we proposed an integrative approach named RAP (Rank Aggregation-based data fusion for gene Prioritization, in which an order statistics-based meta-analysis was used to aggregate the rank of the network-based gene prioritization method and RafSee, for accurately prioritizing candidate genes involved in a pre-specific biological function. Finally, we showcased the utility of RAP by prioritizing 380 flowering-time genes in Arabidopsis. The ‘leave-one-out’ cross-validation experiment showed that RafSee could work as a complement to a current state-of-art network-based gene prioritization system (AraNet v2. Moreover, RAP ranked 53.68% (204/380 flowering-time genes higher than AraNet v2, resulting in an 39.46% improvement in term of the first quartile rank. Further evaluations also showed that RAP was effective in prioritizing genes-related to different abiotic stresses. To enhance the usability of RAP for Arabidopsis and non-model plant species, an R package implementing the method is freely available at http://bioinfo.nwafu.edu.cn/software.

  9. Association of Interleukin-1 gene clusters polymorphisms with primary open-angle glaucoma: a meta-analysis.

    Science.gov (United States)

    Li, Junhua; Feng, Yifan; Sung, Mi Sun; Lee, Tae Hee; Park, Sang Woo

    2017-11-28

    Previous studies have associated the Interleukin-1 (IL-1) gene clusters polymorphisms with the risk of primary open-angle glaucoma (POAG). However, the results were not consistent. Here, we performed a meta-analysis to evaluate the role of IL-1 gene clusters polymorphisms in POAG susceptibility. PubMed, EMBASE and Cochrane Library (up to July 15, 2017) were searched by two independent investigators. All case-control studies investigating the association between single-nucleotide polymorphisms (SNPs) of IL-1 gene clusters and POAG risk were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for quantifying the strength of association that has been involved in at least two studies. Five studies on IL-1β rs16944 (c. -511C > T) (1053 cases and 986 controls), 4 studies on IL-1α rs1800587 (c. -889C > T) (822 cases and 714 controls), and 4 studies on IL-1β rs1143634 (c. +3953C > T) (798 cases and 730 controls) were included. The results suggest that all three SNPs were not associated with POAG risk. Stratification analyses indicated that the rs1143634 has a suggestive associated with high tension glaucoma (HTG) under dominant (P = 0.03), heterozygote (P = 0.04) and allelic models (P = 0.02), however, the weak association was nullified after Bonferroni adjustments for multiple tests. Based on current meta-analysis, we indicated that there is lack of association between the three SNPs of IL-1 and POAG. However, this conclusion should be interpreted with caution and further well designed studies with large sample-size are required to validate the conclusion as low statistical powers.

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

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    Nishi Gupta

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

  11. Association between polymorphisms in ERCC2 gene and oral cancer risk: evidence from a meta-analysis

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    Zhang, Enjiao; Cui, Zhigang; Xu, Zhongfei; Duan, Weiyi; Huang, Shaohui; Tan, Xuexin; Yin, Zhihua; Sun, Changfu; Lu, Li

    2013-01-01

    Excision repair cross-complementing group 2 (ERCC2) plays important roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of ERCC2 gene are suspected to influence the risks of oral cancer. We performed a meta-analysis to systematically summarize the possible association of ERCC2 rs1799793 and rs13181 polymorphisms with oral cancer risks. We retrieved the relevant articles from PubMed and Embase databases. Studies were selected using specific criteria. ORs and 95% CIs were calculated to assess the association. All analyses were performed using the Stata software. Six studies were included in this meta-analysis. There were no significant associations between ERCC2 rs1799793 and rs13181 polymorphism with overall oral cancer risk. In the stratified analysis by ethnicity, no significant associations were found. In the stratified analysis by tumor type, the risk of oral leukoplakia was significant associated with rs13181 polymorphism (AC vs. AA: OR = 1.28, 95% CI = 1.01-1.62, P = 0.546 for heterogeneity, I 2 = 0.0%; CC vs. AA: OR = 1.94, 95% CI = 0.99-3.79, P = 0.057 for heterogeneity, I 2 = 60.1%; dominant model AC + CC vs. AA: OR = 1.35, 95% CI = 1.08–1.69, P = 0.303 for heterogeneity, I 2 = 17.6%; allele C vs. A: OR = 1.38, 95% CI = 1.04–1.82. P = 0.043 for heterogeneity, I 2 = 56.4%). Rs13181 in ERCC2 gene might be associated with oral leukoplakia risk

  12. Meta- analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

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    Wen-Ying; Fan; Ning-Pu; Liu

    2015-01-01

    AIM: To collectively evaluate the association of intercellular adhesion molecule-1(ICAM-1) gene K469 E polymorphism(rs5498) with diabetic retinopathy(DR) in patients with type 2 diabetic mellitus(T2DM). METHODS: Overall review of available literatures relating K469 E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios(ORs). Potential sources of heterogeneity and bias were explored.RESULTS: Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469 E polymorphism with DR(P >0.05). A statistically significant association was detected between the K469 E polymorphism and proliferative DR(PDR) in Asians only in dominant model(GG+AG vs AA) with pooled OR of 0.729(95%CI: 0.564-0.942, P=0.016, P heterogeneity=0.143), however, this association was not detected in recessive model(AG +AA vs GG;OR=1.178, 95%CI: 0.898-1.545, P =0.236, P heterogeneity=0.248)or allelic model(G vs A; OR=0.769, 95% CI: 0.576-1.026,P =0.074, P heterogeneity=0.094). No publication bias was found by Funnel plot, Begg’s and Egger’s test. CONCLUSION: This research found no statistically significant association between ICAM-1 gene K469 E polymorphism and DR in patients with T2 DM, but showed significant association of the K469 E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion.

  13. Prognostic and predictive values of PD-L1 expression in patients with digestive system cancer: a meta-analysis.

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    Dai, Cong; Wang, Meng; Lu, Jun; Dai, Zhiming; Lin, Shuai; Yang, Pengtao; Tian, Tian; Liu, Xinghan; Min, Weili; Dai, Zhijun

    2017-01-01

    PD-L1 has been reported to be expressed in diverse human malignancies. However, the prognostic value of PD-L1 in digestive system cancers remains inconclusive. Therefore, we conducted this meta-analysis to evaluate the prognostic impact of PD-L1 expression in digestive system cancers. We searched the PubMed, Embase, and the Chinese National Knowledge Infrastructure for publications concerning PD-L1 expression in digestive system cancers. Correlations of PD-L1 expression level with overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were analyzed. Finally, 32 studies with 7,308 patients were included. Our results show that PD-L1 expression was significantly associated with poorer OS (hazard ratio [HR] =1.44, 95% confidence interval [CI] =1.18-1.76, P digestive system cancers, especially in gastric cancer and pancreatic cancer. In addition, PD-L1 may act as a new parameter for predicting poor prognosis and a promising target for anticancer therapy in digestive system cancers.

  14. Meta-analysis of genome wide association studies for the stature of cattle reveals numerous common genes that regulate size in mammals

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    Stature is affected by many polymorphisms of small effect in humans but in contrast variation in dogs, even within breeds is largely due to variants in six genes. Here we use data from cattle to compare genetic architecture of stature to that in humans and dogs. We conducted a meta-analysis for stat...

  15. Correlation between leptin receptor gene polymorphism and type 2 diabetes in Chinese population: a meta-analysis

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    Miao HE

    2015-11-01

    Full Text Available Objective To evaluate the correlation between leptin receptor gene (LEPR polymorphism and type 2 diabetes (T2DM in Chinese population. Methods The literature concerning the correlation between LEPR polymorphism and T2DM in Chinese population were searched from Chinese databases (CNKI, VIP, WanFang, CBM with "leptin receptor gene" and "type 2 diabetes" as keywords, and from English databases (PubMed, Web of Knowledge, EBSCO with "leptin receptor gene", "LEPR", "OBR", "OB-R", "type 2 diabetes" and "T2DM" as keywords. The relevant articles were searched up to September 20, 2014. Then, meta-analysis was performed using RevMan 5.1 and Stata 11.0 software. The Newcastle-Ottawa Scale was applied to assess methodological quality of included articles from 3 aspects, namely, selection of participants, comparability and outcome assessment. Results Seventeen case-control studies involving 12 533 cases of T2DM and 3348 controls were included in Meta-analysis. A significant correlation was found between rs1137100 polymorphism in LEPR gene and T2DM (for recessive genetic model: OR=0.67, 95%CI 0.52-0.88, P=0.00; for allele contrast genetic model: OR=1.46, 95%CI 1.15-1.85, P=0.00. A strong correlation was also found between rs1137101 polymorphism and T2DM (for additive genetic model: OR=1.54, 95%CI 1.20-1.98, P=0.00; for allele contrast genetic model: OR=1.15, 95%CI 1.01-1.30, P=0.00. In addition, rs1805096 polymorphism was closely correlated with T2DM (for dominant genetic model: OR=1.32, 95%CI 1.07-1.62, P=0.00; for recessive genetic model: OR=1.30, 95%CI 1.09-1.54, P=0.00; for allele contrast genetic model: OR=0.67, 95%CI 0.59-0.75, P=0.00. Conclusions There is a significant correlation between rs1137100, rs1805096 of LEPR gene and T2DM in Chinese population under allele contrast genetic model as well as in recessive genetic model. Rs1137101 of LEPR gene is closely correlated with T2DM in Chinese population under additive genetic model. For dominant

  16. MUC2 Expression Is Correlated with Tumor Differentiation and Inhibits Tumor Invasion in Gastric Carcinomas: A Systematic Review and Meta-analysis

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    Jung-Soo Pyo

    2015-05-01

    Full Text Available Background: While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinicopathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC. Methods: The present study investigated the correlation between MUC2 expression and clinicopathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. Results: MUC2 expression was found in 58 of 167 GCs (34.7%. MUC2-expressing GC showed lower primary tumor (T, regional lymph node (N, and tumor node metastasis (TNM stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively. However, MUC2 expression was not correlated with Lauren’s classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively but not with Lauren’s classification, pN stage, or pTNM stage. Conclusions: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.

  17. The impact of IGF-1R expression on the outcomes of patients with breast cancer: a meta-analysis

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    Yan S

    2015-01-01

    Full Text Available Shunchao Yan,1 Xin Jiao,2 Kai Li,1 Wusheng Li,1 Huawei Zou11Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Respiratory Medicine, Shenyang Chest Hospital, Shenyang, People’s Republic of ChinaPurpose: The value of insulin-like growth factor 1 receptor (IGF-1R for predicting survival of patients with breast cancer remains controversial. The purpose of this study was to perform a meta-analysis of the published data to attempt to clarify the impact of IGF-1R.Methods: Studies published between January 1, 1990 and October 1, 2014 were identified using an electronic search to aggregate the available survival results. Studies were included if they reported detecting IGF-1R expression in the primary breast cancer and analyzed patient survival data according to IGF-1R status. The principal outcome measures were hazard ratios (HRs for survival of IGF-1R-positive patients. Combined HRs and 95% confidence intervals (CIs were estimated using fixed- or random-effects models according to between-study heterogeneity.Results: Ten studies, involving 5,406 patients, satisfied our inclusion criteria. Data from five studies provided the impact of IGF-1R on overall survival (OS, three studies the impact on breast cancer-specific survival (BCSS, and seven studies the impact on disease-free survival (DFS. The results of meta-analysis showed that for DFS, membranous IGF-1R positivity was not a significant predictor. The combined HR for OS/BCSS was 0.63 (95% CI: 0.42–0.95, P=0.03, indicating that membranous IGF-1R positivity was a significant predictor of better survival. IGF-1R cytoplasmic positivity was significantly associated with longer DFS and OS/BCSS (combined HR: 0.56, 95% CI: 0.35–0.89, P=0.01; combined HR: 0.55, 95% CI: 0.35–0.85, P=0.008, respectively. The results of subgroup analysis suggested that membranous IGF-1R positivity in hormone-receptor-positive breast cancer was

  18. A meta-analysis of data associating DRD4 gene polymorphisms with schizophrenia

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    Xu F

    2018-01-01

    Full Text Available Feng-ling Xu, Xue Wu, Jing-jing Zhang, Bao-jie Wang, Jun Yao Department of Forensic, Genetic and Biology Medicine, School of Forensic Medicine, China Medical University, Shenyang, China Abstract: To explore the association between DRD4 polymorphisms and schizophrenia risk, a meta-analysis was carried out with 41 case–control articles. Specifically, we included 28 articles (5,735 cases and 5,278 controls that pertained to the 48 bp variable number tandem repeat (VNTR polymorphism, nine articles (1,517 cases and 1,746 controls that corresponded to the 12 bp tandem repeat (TR, six articles (1,912 cases and 1,836 controls that addressed the 120 bp TR, 10 articles (2,927 cases and 2,938 controls that entailed the −521 C>T polymorphism, six articles (1,735 cases and 1,724 controls that pertained to the −616 C>G polymorphism, and four articles (1,191 cases and 1,215 controls that involved the −376 C>T polymorphism. Pooled analysis, subgroup analysis, and sensitivity analysis were performed, and the data were visualized by means of forest and funnel plots. Results of pooled analysis indicated that the -521 CC variant (Pz=0.009, odds ratio [OR] =1.218, 95% confidence interval [CI] =1.050–1.413 and genotype L/L (ie, long allele of the 120 bp TR were risk factors of schizophrenia (Pz=0.004, OR =1.275, 95% CI =1.081–1.504. The 48 bp VNTR, the 12 bp TR, the −616 C>G polymorphism, and the −376 C>T polymorphism were not associated with schizophrenia. Additional research is warranted to explore the association between polymorphisms of DRD4 and schizophrenia risk. Keywords: DRD4, schizophrenia, meta-analysis, polymorphism

  19. Association between TNF-α-238G/A gene polymorphism and OCD susceptibility: A meta-analysis.

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    Jiang, Caixiao; Ma, Xinyan; Qi, Shunxiang; Han, Guangyue; Li, Yan; Liu, Yanfang; Liu, Lanfen

    2018-02-01

    Tumor necrosis factor-alpha (TNF-α) is an important cytokine and has been reported to be associated with the pathogenesis of many autoimmune and inflammatory diseases. TNF-α gene is located on a region that has been found to be associated with obsessive-compulsive disorder (OCD). We performed this meta-analysis to assess the relationship between susceptibility to OCD and the TNF-α-238G/A gene polymorphism. An extensive search of the available literature on the association between the susceptibility to OCD and the TNF gene polymorphism was conducted by searching PubMed, Web of Knowledge, Embase, Chinese Web of Knowledge, Wanfang, and Chongqing VIP database. The database was searched up to December 2016 and includes language of English and/or Chinese with the keywords of "obsessive-compulsive disorder" or "OCD," polymorphism or variant or mutation, "tumor necrosis factor" or "TNF" or "cytokine." The association between TNF-α-238G/A gene polymorphism and the susceptibility of OCD was anticipated by odds ratio (OR) with the corresponding 95% confidence interval (95% CI). Four studies including 435 cases and 1073 controls were incorporated in our meta-analysis. In general, TNF-α-238G/A gene polymorphism might lead to a decreased risk of OCD susceptibility (G vs A genotype model: OR = 1.01, 95% CI = 0.37-2.77, P = .981; GG vs AA+AG model: OR = 0.93, 95% CI = 0.37-2.36, P = .879; GG+AG vs AA model: OR = 0.22, 95% CI = 0.06-0.73, P = .014; GG vs AA model: OR = 0.21, 95% CI = 0.06-0.71, P = .012; AG vs AA model: OR = 0.29, 95% CI = 0.07-1.16, P = .081; GG+AA vs AG model: OR = 1.17, 95% CI = 0.55-2.51, P = .683). TNF-α-238G/A gene polymorphism might lead to a decreased risk of OCD susceptibility.

  20. Prognostic value of HER-2/neu expression in epithelial ovarian cancer: a systematic review and meta-analysis.

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    Wang, Kai; Guan, Chenan; Yu, Junhui; Jin, Xiaoxiao; Sun, Ling; Zheng, Lingzhi; Xia, Liang; Zhang, Yuquan

    2017-09-26

    This study aimed to conduct a meta-analysis to investigate the association between human epidermal growth factor receptor 2 (HER-2/neu) expression and survival in patients with epithelial ovarian cancer (EOC). HER-2/neu is one of the most frequently studied molecular biological parameters in EOC, but its prognostic impact has not been fully assessed. PubMed and Embase were searched for studies that reported HER-2/neu expression and survival in patients with EOC. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Hazard ratios (HRs) with 95% confidence interval (CI) were determined using Mantel-Haenszel random-effects model. Publication bias was investigated using funnel plots and Egger's test. A total of 56 studies (N=7212) were included in the analysis. The results showed that patients possessing HER-2/neu expression had significant disadvantages in OS (HR = 1.41; 95%CI, 1.31 to 1.51; P present study findings provided further indication that HER-2/neu expression in patients with EOC has an adverse impact on OS and PFS.

  1. Mink S38G Gene Polymorphism and Atrial Fibrillation in the Chinese Population: A Meta-Analysis of 1871 Participants

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    Yan-yan Li

    2014-01-01

    Full Text Available Mink gene S38G polymorphism in the β-subunit of slow activating component of the delayed rectifier potassium channel current potassium channel has been associated with increased atrial fibrillation (AF risk. However, the individual studies results were still controversial. To investigate the association of Mink S38G gene polymorphisms with AF, a meta-analysis including 1871 subjects from six individual studies was conducted. Mink S38G gene polymorphism was significantly related to AF under allelic (OR: 1.380, 95% CI: 1.200–1.600, P<0.00001, recessive (OR: 1.193, 95% CI: 1.033–1.377, P=0.017, dominant (OR: 1.057, 95% CI: 1.025–1.089, P<0.00001, additive (OR: 1.105, 95% CI: 1.036–1.178, P=0.002, homozygous (OR: 1.128, 95% CI: 1.068–1.191, P<0.00001, and heterozygous genetic models (OR: 1.078, 95% CI: 1.014–1.146, P=0.016. A significant association between Mink S38G gene polymorphism and AF risk was found. G allele carriers may predispose to AF.

  2. Mutations in the HFE gene and sporadic amyotrophic lateral sclerosis risk: a meta-analysis of observational studies

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    M. Li

    2014-03-01

    Full Text Available Iron homeostasis dysregulation has been regarded as an important mechanism in neurodegenerative diseases. The H63D and C282Y polymorphisms in the HFE gene may be involved in the development of sporadic amyotrophic lateral sclerosis (ALS through the disruption of iron homeostasis. However, studies investigating the relationship between ALS and these two polymorphisms have yielded contradictory outcomes. We performed a meta-analysis to assess the roles of the H63D and C282Y polymorphisms of HFE in ALS susceptibility. PubMed, MEDLINE, EMBASE, and Cochrane Library databases were systematically searched to identify relevant studies. Strict selection criteria and exclusion criteria were applied. Odds ratios (ORs with 95% confidence intervals (CIs were used to assess the strength of associations. A fixed- or random-effect model was selected, depending on the results of the heterogeneity test. Fourteen studies were included in the meta-analysis (six studies with 1692 cases and 8359 controls for C282Y; 14 studies with 5849 cases and 13,710 controls for H63D. For the C282Y polymorphism, significant associations were observed in the allele model (Y vs C: OR=0.76, 95%CI=0.62-0.92, P=0.005 and the dominant model (YY+CY vs CC: OR=0.75, 95%CI=0.61-0.92, P=0.006. No associations were found for any genetic model for the H63D polymorphism. The C282Y polymorphism in HFE could be a potential protective factor for ALS in Caucasians. However, the H63D polymorphism does not appear to be associated with ALS.

  3. Association between allelic variants of the human glucocorticoid receptor gene and autoimmune diseases: A systematic review and meta-analysis.

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    Herrera, Cristian; Marcos, Miguel; Carbonell, Cristina; Mirón-Canelo, José Antonio; Espinosa, Gerard; Cervera, Ricard; Chamorro, Antonio-Javier

    2018-05-01

    The human glucocorticoid receptor gene (NR3C1) is considered to play a role in the differences and sensitivities of the glucocorticoid response in individuals with autoimmune diseases. The objective of this study was to examine by means of a systematic review previous findings regarding allelic variants of NR3C1 in relation to the risk of developing systemic autoimmune diseases. Studies that analysed the genotype distribution of NR3C1 allelic variants among patients with systemic autoimmune diseases were retrieved. A meta-analysis was conducted with a random effects model. Odds ratios (ORs) and their confidence intervals (CIs) were calculated. In addition, sub-analysis by ethnicity, sensitivity analysis and tests for heterogeneity of the results were performed. Eleven studies met the inclusion criteria for meta-analysis. We found no evidence that the analysed NR3C1 polymorphisms, rs6198, rs56149945, and rs6189/rs6190, modulate the risk of developing a systemic autoimmune disease. Nonetheless, a protective role for the minor allele of rs41423247 was found among Caucasians (OR=0.78; 95% CI: 0.65, 0.92; P=0.004). A subgroup analysis according to underlying diseases revealed no significant association either for Behçet's disease or rheumatoid arthritis, while correlations between NR3C1 polymorphisms and disease activity or response to glucocorticoids could not be evaluated due to insufficient data. There is no clear evidence that the analysed NR3C1 allelic variants confer a risk for developing systemic autoimmune diseases although the minor G allele of rs41423247 may be protective among Caucasians. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Meta-Analysis of Microarray Data Identifies GAS6 Expression as an Independent Predictor of Poor Survival in Ovarian Cancer

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    Michelle Buehler

    2013-01-01

    Full Text Available Seeking new biomarkers for epithelial ovarian cancer, the fifth most common cause of death from all cancers in women and the leading cause of death from gynaecological malignancies, we performed a meta-analysis of three independent studies and compared the results in regard to clinicopathological parameters. This analysis revealed that GAS6 was highly expressed in ovarian cancer and therefore was selected as our candidate of choice. GAS6 encodes a secreted protein involved in physiological processes including cell proliferation, chemotaxis, and cell survival. We performed immunohistochemistry on various ovarian cancer tissues and found that GAS6 expression was elevated in tumour tissue samples compared to healthy control samples (. In addition, GAS6 expression was also higher in tumours from patients with residual disease compared to those without. Our data propose GAS6 as an independent predictor of poor survival, suggesting GAS6, both on the mRNA and on the protein level, as a potential biomarker for ovarian cancer. In clinical practice, the staining of a tumour biopsy for GAS6 may be useful to assess cancer prognosis and/or to monitor disease progression.

  5. Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis.

    Science.gov (United States)

    Wang, Qingzhong; Shelton, Richard C; Dwivedi, Yogesh

    2018-01-01

    Gene-environment interaction contributes to the risks of psychiatric disorders. Interactions between FKBP5 gene variants and early-life stress may enhance the risk not only for mood disorder, but also for a number of other behavioral phenotypes. The aim of the present study was to review and conduct a meta-analysis on the results from published studies examining interaction between FKBP5 gene variants and early-life stress and their associations with stress-related disorders such as major depression and PTSD. A literature search was conducted using PsychINFO and PubMed databases until May 2017. A total of 14 studies with a pooled total of 15109 participants met the inclusion criteria, the results of which were combined and a meta-analysis was performed using the differences in correlations as the effect measure. Based on literature, rs1360780, rs3800373, and rs9470080 SNPs were selected within the FKBP5 gene and systematic review was conducted. Based on the Comprehensive Meta-Analysis software, no publication bias was detected. Sensitivity analysis and credibility of meta-analysis results also indicated that the analyses were stable. The meta-analysis showed that individuals who carry T allele of rs1360780, C-allele of rs3800373 or T-allele of rs9470080 exposed to early-life trauma had higher risks for depression or PTSD. The effects of ethnicity, age, sex, and different stress measures were not examined due to limited sample size. These results provide strong evidence of interactions between FKBP5 genotypes and early-life stress, which could pose a significant risk factor for stress-associated disorders such as major depression and PTSD. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Association between CD14 gene C-260T polymorphism and inflammatory bowel disease: a meta-analysis.

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    Zhengting Wang

    Full Text Available BACKGROUND: The gene encoding CD14 has been proposed as an IBD-susceptibility gene with its polymorphism C-260T being widely evaluated, yet with conflicting results. The aim of this study was to investigate the association between this polymorphism and IBD by conducting a meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Seventeen articles met the inclusion criteria, which included a total of 18 case-control studies, including 1900 ulcerative colitis (UC cases, 2535 Crohn's disease (CD cases, and 4004 controls. Data were analyzed using STATA software. Overall, association between C-260T polymorphism and increased UC risk was significant in allelic comparison (odds ratio [OR]  =1.21, 95% confidence interval [CI]: 1.02-1.43; P=0.027, homozygote model (OR  =1.44, 95% CI: 1.03-2.01; P=0.033, as well as dominant model (OR  =1.36, 95% CI: 1.06-1.75; P=0.016. However, there was negative association between this polymorphism and CD risk across all genetic models. Subgroup analyses by ethnicity suggested the risk-conferring profiles of -260T allele and -260 TT genotype with UC in Asians, but not in Caucasians. There was a low probability of publication bias. CONCLUSIONS/SIGNIFICANCE: Expanding previous results of individual studies, our findings demonstrated that CD14 gene C-260T polymorphism might be a promising candidate marker in susceptibility to UC, especially in Asians.

  7. Meta-analysis of archived DNA microarrays identifies genes regulated by hypoxia and involved in a metastatic phenotype in cancer cells

    International Nuclear Information System (INIS)

    Pierre, Michael; DeHertogh, Benoît; Gaigneaux, Anthoula; DeMeulder, Bertrand; Berger, Fabrice; Bareke, Eric; Michiels, Carine; Depiereux, Eric

    2010-01-01

    Metastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear. Another key feature of a tumor is the presence of hypoxic areas caused by a lack of oxygen at the center of the tumor. Hypoxia leads to the expression of pro-metastatic genes as well as the repression of anti-metastatic genes. As many Affymetrix datasets about metastasis and hypoxia are publicly available and not fully exploited, this study proposes to re-analyze these datasets to extract new information about the metastatic phenotype induced by hypoxia in different cancer cell lines. Affymetrix datasets about metastasis and/or hypoxia were downloaded from GEO and ArrayExpress. AffyProbeMiner and GCRMA packages were used for pre-processing and the Window Welch t test was used for processing. Three approaches of meta-analysis were eventually used for the selection of genes of interest. Three complementary approaches were used, that eventually selected 183 genes of interest. Out of these 183 genes, 99, among which the well known JUNB, FOS and TP63, have already been described in the literature to be involved in cancer. Moreover, 39 genes of those, such as SERPINE1 and MMP7, are known to regulate metastasis. Twenty-one genes including VEGFA and ID2 have also been described to be involved in the response to hypoxia. Lastly, DAVID classified those 183 genes in 24 different pathways, among which 8 are directly related to cancer while 5 others are related to proliferation and cell motility. A negative control composed of 183 random genes failed to provide such results. Interestingly, 6 pathways retrieved by DAVID with the 183 genes of interest concern pathogen recognition and phagocytosis. The proposed methodology was able to find genes actually known to be involved in cancer, metastasis and hypoxia and, thus, we propose that the other genes selected based on the same methodology are of prime interest in

  8. Glutathione S-transferase P1, gene-gene interaction, and lung cancer susceptibility in the Chinese population: An updated meta-analysis and review

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    Xue-Ming Li

    2015-01-01

    Full Text Available Aim of Study: To assess the impact of glutathione S-transferase P1 (GSTP1 Ile105Val polymorphism on the risk of lung cancer in the Chinese population, an updated meta-analysis and review was performed. Materials and Methods: Relevant studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine published through January 22, 2015. The odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the strength of the associations. Results: A total of 13 case-control studies, including 2026 lung cancer cases and 2451 controls, were included in this meta-analysis. Overall, significantly increased lung cancer risk was associated with the variant genotypes of GSTP1 polymorphism in the Chinese population (GG vs. AA: OR = 1.36, 95% CI = 1.01-1.84. In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies (GG vs. AA: OR = 1.62, 95% CI: 1.13-2.31; GG vs. AG: OR = 1.49, 95% CI: 1.03-2.16; GG vs. AA + AG: OR = 1.55, 95% CI: 1.12-2.26. A gene-gene interaction analysis showed that there was an interaction for individuals with combination of GSTM1 (or GSTT1 null genotype and GSTP1 (AG + GG mutant genotype for lung cancer risk in Chinese. Conclusion: This meta-analysis suggests that GSTP1 Ile105Val polymorphism may increase the risk of lung cancer in the Chinese population.

  9. The impact of IGF-1R expression on the outcomes of patients with breast cancer: a meta-analysis

    Science.gov (United States)

    Yan, Shunchao; Jiao, Xin; Li, Kai; Li, Wusheng; Zou, Huawei

    2015-01-01

    Purpose The value of insulin-like growth factor 1 receptor (IGF-1R) for predicting survival of patients with breast cancer remains controversial. The purpose of this study was to perform a meta-analysis of the published data to attempt to clarify the impact of IGF-1R. Methods Studies published between January 1, 1990 and October 1, 2014 were identified using an electronic search to aggregate the available survival results. Studies were included if they reported detecting IGF-1R expression in the primary breast cancer and analyzed patient survival data according to IGF-1R status. The principal outcome measures were hazard ratios (HRs) for survival of IGF-1R-positive patients. Combined HRs and 95% confidence intervals (CIs) were estimated using fixed- or random-effects models according to between-study heterogeneity. Results Ten studies, involving 5,406 patients, satisfied our inclusion criteria. Data from five studies provided the impact of IGF-1R on overall survival (OS), three studies the impact on breast cancer-specific survival (BCSS), and seven studies the impact on disease-free survival (DFS). The results of meta-analysis showed that for DFS, membranous IGF-1R positivity was not a significant predictor. The combined HR for OS/BCSS was 0.63 (95% CI: 0.42–0.95, P=0.03), indicating that membranous IGF-1R positivity was a significant predictor of better survival. IGF-1R cytoplasmic positivity was significantly associated with longer DFS and OS/BCSS (combined HR: 0.56, 95% CI: 0.35–0.89, P=0.01; combined HR: 0.55, 95% CI: 0.35–0.85, P=0.008, respectively). The results of subgroup analysis suggested that membranous IGF-1R positivity in hormone-receptor-positive breast cancer was correlated with favorable DFS (combined HR: 0.61, 95% CI: 0.41–0.92, P=0.02) and OS/BCSS (combined HR: 0.73, 95% CI: 0.57–0.93, P=0.01). Membranous IGF-1R positivity in triple-negative breast cancer predicted worse DFS (combined HR: 1.86, 95% CI: 1.03–3.34, P=0.04). Membranous

  10. Association between ADAM metallopeptidase domain 33 gene polymorphism and risk of childhood asthma: a meta-analysis.

    Science.gov (United States)

    Sun, F J; Zou, L Y; Tong, D M; Lu, X Y; Li, J; Deng, C B

    2017-08-31

    This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.

  11. BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction.

    Science.gov (United States)

    Zhao, Mingzhe; Chen, Lu; Yang, Jiarun; Han, Dong; Fang, Deyu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Ma, Jingsong; Wang, Lin; Jiang, Shixiang; Song, Xuejia; Zhou, Jiawei; Zhang, Jian; Chen, Mingqi; Qi, Dong; Yang, Yanjie; Pan, Hui

    2018-02-01

    Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Serine/threonine kinase 15 gene polymorphism and risk of digestive system cancers: A meta-analysis.

    Science.gov (United States)

    Luo, Jianfei; Yan, Ruicheng; Zou, Li

    2015-01-01

    Previous studies have reported an association between the two coding polymorphisms (91T>A and 169G>A) of the serine/threonine kinase 15 (STK15) gene and the risk of digestive system cancers; however, the results are inconsistent. In the present study, a meta-analysis was carried out to assess the association between the two STK15 polymorphisms and the risk of digestive system cancers. Relevant studies were identified using PubMed, Web of Science, China National Knowledge Infrastructure, WanFang and VIP databases up to February 18, 2014. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed or random effects model. A total of 15 case-control studies from 14 publications were included. Of these, 15 studies concerned the 91T>A polymorphism and included 7,619 cases and 7,196 controls and four studies concerned the 161G>A polymorphism and included 826 cases and 713 controls. A significantly increased risk of digestive system cancers was observed for the 91T>A polymorphism (recessive model: OR, 1.19; 95% CI, 1.07-1.31). In subgroup analysis by ethnicity, a significant association was detected in Asian populations (recessive model: OR, 1.21; 95% CI, 1.08-1.36) but not in Caucasian and mixed populations. Stratification by tumor type indicated that the 91T>A polymorphism was associated with an increased risk of esophageal and colorectal cancers under the recessive model (OR, 1.19; 95% CI, 1.03-1.38; and OR, 1.24; 95% CI, 1.04-1.46; respectively); however, no significant association was observed between the 169G>A polymorphism and the risk of digestive system cancers in any of the genetic models. Furthermore, in subgroup analysis by ethnicity, similar results were observed in the Asian and Caucasian populations. The present meta-analysis demonstrated that the STK15 gene 91T>A polymorphism, but not the 169G>A polymorphism, may be a risk factor for digestive system cancers, particularly for esophageal and colorectal cancers.

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

    Directory of Open Access Journals (Sweden)

    Shujie Guo

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

  14. Prognostic value of CD166 expression in cancers of the digestive system: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Chao Ni

    Full Text Available Many studies have reported the prognostic predictive value of CD166 as a cancer stem cell marker in cancers of the digestive system; however, its predictive value remains controversial. Here, we investigate the correlation between CD166 positivity in digestive system cancers and clinicopathological features using meta-analysis.A comprehensive search in PubMed and ISI Web of Science through March of 2013 was performed. Only articles containing CD166 antigen immunohistochemical staining in cancers of the digestive system were included,including pancreatic cancer, esophageal cancer, gastric cancer and colorectal cancer. Data comparing 3- and 5-year overall survival along with other clinicopathological features were collected.Nine studies with 2553 patients who met the inclusion criteria were included for the analysis. The median rate of CD166 immunohistochemical staining expression was 56% (25.4%-76.3%. In colorectal cancer specifically, the results of a fixed-effects model indicated that CD166-positive expression was an independent marker associated with a smaller tumor burden (T category; RR = 0.93, 95%, CI: 0.88-0.98 but worse spread to nearby lymph nodes (N category; RR = 1.17, 95% CI: 1.05-1.30. The 5-year overall survival rate was showed relationship with cytoplasmic positive staining of CD166 (RR = 1.47 95% 1.21-1.79, but no significant association was found in the pool or any other stratified analysis with 3- or 5- year overall survival rate.Based on the published studies, different cellular location of CD166 has distinct prognostic value and cytoplasmic positive expression is associated with worse prognosis outcome. Besides, our results also find CD166 expression indicate advanced T category and N-positive status in colorectal cancer specifically.

  15. Genetic polymorphisms of xeroderma pigmentosum group D gene Asp312Asn and Lys751Gln and susceptibility to prostate cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Ma, Qingtong; Qi, Can; Tie, Chong; Guo, Zhanjun

    2013-11-10

    Many studies have reported the role of xeroderma pigmentosum group D (XPD) with prostate cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. A total of 8 studies including 2620 cases and 3225 controls described Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582 controls described Lys751Gln genotypes and were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, a significant association between prostate cancer risk and XPD Asp312Asn polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by ethnicity and source of controls, prostate cancer risk was observed in co-dominant, dominant and recessive models, while no evidence of any associations of XPD Lys751Gln polymorphism with prostate cancer was found in the overall or subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism contributed to the risk of prostate cancer from currently available evidence. However, a study with a larger sample size is needed to further evaluate gene-environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. © 2013.

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

    Science.gov (United States)

    Zeng, Tianshu; Cai, Xiong; Kong, Wen

    2017-01-01

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

  17. 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.

  18. Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions.

    Science.gov (United States)

    Leppanen, Jenni; Ng, Kah Wee; Tchanturia, Kate; Treasure, Janet

    2017-07-01

    Accurate interpretation and appropriate expression of emotions are key aspects of social-cognition. Several mental disorders are characterised by transdiagnostic difficulties in these areas and, recently, there has been increasing interest in exploring the effects of oxytocin on social-emotional functioning. This review consists of 33 studies. Fifteen of the studies included people with autism spectrum disorder, schizophrenia, borderline personality disorder, frontotemporal dementia, anorexia nervosa, bulimia nervosa, post-traumatic stress disorder, depression, and opioid and alcohol dependence. We conducted ten meta-analyses examining the effects of intranasal oxytocin on expression of emotions, emotional theory of mind, sensitivity to recognise basic emotions, and recognition of basic emotions. A single dose of intranasal oxytocin significantly improved the recognition of basic emotions, particularly fear, and increased the expression of positive emotions among the healthy individuals. Oxytocin did not significantly influence theory of mind or the expression of negative emotions among the healthy individuals. Finally, intranasal oxytocin did not significantly influence interpretation or expression of emotions among the clinical populations. Copyright © 2017. Published by Elsevier Ltd.

  19. Use of meta-analysis to combine candidate gene association studies: application to study the relationship between the ESR PvuII polymorphism and sow litter size

    Directory of Open Access Journals (Sweden)

    Alfonso Leopoldo

    2005-07-01

    Full Text Available Abstract This article investigates the application of meta-analysis on livestock candidate gene effects. The PvuII polymorphism of the ESR gene is used as an example. The association among ESR PvuII alleles with the number of piglets born alive and total born in the first (NBA1, TNB1 and later parities (NBA, TNB is reviewed by conducting a meta-analysis of 15 published studies including 9329 sows. Under a fixed effects model, litter size values were significantly lower in the "AA" genotype groups when compared with "AB" and "BB" homozygotes. Under the random effects model, the results were similar although differences between "AA" and "AB" genotype groups were not clearly significant for NBA and TNB. Nevertheless, the most noticeable result was the high and significant heterogeneity estimated among studies. This heterogeneity could be assigned to error sampling, genotype by environment interaction, linkage or epistasis, as referred to in the literature, but also to the hypothesis of population admixture/stratification. It is concluded that meta-analysis can be considered as a helpful analytical tool to synthesise and discuss livestock candidate gene effects. The main difficulty found was the insufficient information on the standard errors of the estimated genotype effects in several publications. Consequently, the convenience of publishing the standard errors or the concrete P-values instead of the test significance level should be recommended to guarantee the quality of candidate gene effect meta-analyses.

  20. Significance of CD44 expression in head and neck cancer: a systemic review and meta-analysis

    International Nuclear Information System (INIS)

    Chen, Jianqiang; Zhou, Jianding; Lu, Jie; Xiong, Hua; Shi, Xueli; Gong, Liang

    2014-01-01

    CD44 has been reported to be involved with tumor growth and metastasis and has also been implicated as a CSC marker in head and neck squamous cell cancer (HNSCC). However, the prognostic value of CD44 still remains controversial; hence, we investigated the correlation between CD44 and the clinicopathological features of HNSCC by meta-analysis. A comprehensive search was performed using PubMed, ISI web of Science and China National Knowledge Infrastructure (CNKI) up to April 2013. Only studies with immunohistochemical staining of HNSCC were considered. Data on TNM classification, tumor grade, disease free survival and 3- or 5-year overall survival rate were extracted. Thirty studies with 2102 patients met the inclusion criteria for the meta-analysis. Fifteen studies used anti-pan-CD44 antibody, 9 used anti-CD44-v6 antibody, 2 used anti-CD44-v3 and 2 used anti-CD44s antibody, 1 used anti-CD44-v9, and 1 used anti-CD44-v6,-v3 and -v4-5 simultaneously. The total percentage of CD44 expression was 57.8%, with 49.3% in oral cancer patients, 66.4% in pharynx and 54.7% in larynx cancer patients expressing CD44. No significant correlation between clinical features and CD44 expression was revealed for oral cancer patients, but CD44 was shown to be associated with advanced T categories (larynx: RR = 1.33, 95% CI 1.01-1.76; larynx & pharynx RR = 1.21, 95% CI 1.08-1.35), worse N categories (larynx: RR = 2.53, 95% CI 1.99-3.21; larynx & pharynx RR = 1.95, 95% CI 1.35-2.82), higher tumor grades (larynx & pharynx RR = 1.71, 95% CI 1.04-2.79) and 5-year OS rates (larynx: RR = 0.62, 95% CI 0.47-0.83; larynx & pharynx RR = 0.66, 95% CI 0.47-0.94) in patients with laryngeal and pharyngolaryngeal cancer. In stratified analysis, pan-CD44 and CD44-v6 expression were both correlated with 5-year OS rate of patients with laryngeal (CD44: RR = 0.66, 95% CI 0.46-0.95; CD44-v6 RR = 0.53, 95% CI 0.37-0.77) and pharyngolaryngeal cancer (CD44: RR = 0.56, 95% CI 0.34-0.93; CD44-v6 RR = 0.53, 95% CI

  1. The ABCG2 gene Q141K polymorphism contributes to an increased risk of gout: a meta-analysis of 2185 cases.

    Science.gov (United States)

    Qiu, Ya; Liu, Hua; Qing, Yufeng; Yang, Min; Tan, Xiaoyao; Zhao, Mingcai; Lin, Monica; Zhou, Jingguo

    2014-09-01

    Individual genetic association studies examining the relationship between the ABCG2 gene polymorphisms and gout have yielded inconsistent results. This study aims to evaluate the association between the ABCG2 gene variants and gout using meta-analysis. Relevant studies were identified by searching databases extensively. The odds ratio (OR) was calculated using a random-effect or fixed-effect model. A Q statistic was used to evaluate homogeneity, and Egger's test and funnel plot were used to assess publication bias. Subgroup analyses on ethnicities and sex were also performed. A total of 7 studies, including 2185 gout patients and 8028 controls from 5 countries or regions, were included and identified for the current meta-analysis. It was found that the A allele or AA genotype of the ABCG2 Q141K polymorphism (rs2231142) had an increased risk of gout in the general population (A allele, p gout (p gout.

  2. Written Expression in Individuals with Autism Spectrum Disorder: A Meta-Analysis

    Science.gov (United States)

    Finnegan, Elizabeth; Accardo, Amy L.

    2018-01-01

    Although studies exist measuring the effectiveness of writing interventions for students with autism spectrum disorder (ASD), research assessing the writing skills for this group is sparse. The present study identified differences in the written expression of individuals with ASD compared to typically developing (TD) peers, using variables…

  3. Relationship between -889 C/T polymorphism in interleukin-1A gene and risk of chronic periodontitis: Evidence from a meta-analysis with new published findings.

    Science.gov (United States)

    da Silva, F-R-P; Guimarães-Vasconcelos, A-C-C; de-Carvalho-França, L-F; di-Lenardo, D; Rodrigues, L-S; Barreto-do-Nascimento, M-L-L; Vasconcelos, D-F-P

    2017-01-01

    Periodontitis results from an inflammatory response caused by accumulative microorganisms in periodontal sites. Several factors are involved in pathogenesis of periodontitis, for example the -889 C/T polymorphism in interleukin-1A gene. This study aimed to evaluate the relationship between this polymorphism and risk of development of chronic periodontitis by a meta-analysis based in new published findings. Thereunto a review in literature was performed in the electronic biomedical and education databases (Cochrane Library, Google Scholar, MEDLINE and PubMed) to studies published before August 2, 2015, the abstracts were evaluated and the data extraction performed by two calibrated examiners. The calculations of the meta-analysis were obtained through statistical software Review Manager version 5.2 with calculation of Odds Ratio (OR), heterogeneity (I²) and Funnel plots with P chronic periodontitis and 1, 756 controls. The meta-analysis showed T allele was associated with chronic periodontitis (OR = 1.22, 95% CI: 1.09, 1.36, P = 0.0004) with decreased value to heterogeneity (I² = 15%, P = 0.28). TT genotype was associated to patients with chronic periodontitis (OR = 1.40, 95% CI: 1.07, 1.83, P = 0.01). No publication bias was found in this meta-analysis by asymmetry in Funnel plots. This meta-analysis with 2,174 patients with chronic periodontitis and 1, 756 controls evidenced the -889 C/T polymorphism is associated to risk of development of chronic periodontitis with no significant value to heterogeneity to allelic evaluation.

  4. Global meta-analysis of transcriptomics studies.

    Directory of Open Access Journals (Sweden)

    José Caldas

    Full Text Available Transcriptomics meta-analysis aims at re-using existing data to derive novel biological hypotheses, and is motivated by the public availability of a large number of independent studies. Current methods are based on breaking down studies into multiple comparisons between phenotypes (e.g. disease vs. healthy, based on the studies' experimental designs, followed by computing the overlap between the resulting differential expression signatures. While useful, in this methodology each study yields multiple independent phenotype comparisons, and connections are established not between studies, but rather between subsets of the studies corresponding to phenotype comparisons. We propose a rank-based statistical meta-analysis framework that establishes global connections between transcriptomics studies without breaking down studies into sets of phenotype comparisons. By using a rank product method, our framework extracts global features from each study, corresponding to genes that are consistently among the most expressed or differentially expressed genes in that study. Those features are then statistically modelled via a term-frequency inverse-document frequency (TF-IDF model, which is then used for connecting studies. Our framework is fast and parameter-free; when applied to large collections of Homo sapiens and Streptococcus pneumoniae transcriptomics studies, it performs better than similarity-based approaches in retrieving related studies, using a Medical Subject Headings gold standard. Finally, we highlight via case studies how the framework can be used to derive novel biological hypotheses regarding related studies and the genes that drive those connections. Our proposed statistical framework shows that it is possible to perform a meta-analysis of transcriptomics studies with arbitrary experimental designs by deriving global expression features rather than decomposing studies into multiple phenotype comparisons.

  5. Geographical and Ethnic Distributions of the MTHFR C677T, A1298C and MTRR A66G Gene Polymorphisms in Chinese Populations: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Xingmin Wang

    Full Text Available The geographical and ethnic distributions of the polymorphic methylenetetrahydrofolate reductase (MTHFR mutations (C677T and A1298C and methionine synthase reductase (MTRR mutation (A66G remain heterogeneous in China. The goal of this study was to estimate the pooled frequencies of the alleles and associated genotypes of these gene polymorphisms among healthy populations in Mainland China.We systematically reviewed published epidemiological studies on the distributions of 3 genetic variants in Chinese healthy populations living in Mainland China through a meta-analysis. The relevant electronic databases were searched. All of the raw data of the eligible citations were extracted. The frequency estimates were stratified by geography, ethnicity and sex.Sixty-six studies were identified with a total of 92277 study participants. The meta-analysis revealed that the frequencies of the MTHFR C677T, A1298C, and MTRR A66G gene polymorphisms varied significantly between different ethnic groups and along geographical gradients. The frequencies of the 677T allele and 677TT genotype increased along the southern-central-northern direction across Mainland China (all Pvalues≤0.001. The frequencies of the 1298C, 1298CC, 66G and 66GG genotypes decreased along the south-central-north direction across the country (all Pvalues≤0.001.Our meta-analysis strongly indicates significant geographical and ethnic variations in the frequencies of the C677T, A1298C, and A66G gene polymorphisms in the folate metabolism pathway among Chinese populations.

  6. A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS

    NARCIS (Netherlands)

    Wills, A-M.; Cronin, S.; Slowik, A.; Kasperaviciute, D.; Van Es, M. A.; Morahan, J. M.; Valdmanis, P. N.; Meininger, V.; Melki, J.; Shaw, C. E.; Rouleau, G. A.; Fisher, E. M. C.; Shaw, P. J.; Morrison, K. E.; Pamphlett, R.; Van den Berg, L. H.; Figlewicz, D. A.; Andersen, P. M.; Al-Chalabi, A.; Hardiman, O.; Purcell, S.; Landers, J. E.; Brown, R. H.

    2009-01-01

    Background: Six candidate gene studies report a genetic association of DNA variants within the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). However, several other large studies, including five genome-wide association studies, have not duplicated this finding. Methods: We

  7. Association of endothelial nitric oxide synthase gene polymorphisms with coronary artery disease: an updated meta-analysis and systematic review.

    Directory of Open Access Journals (Sweden)

    Himanshu Rai

    Full Text Available Several association studies of endothelial nitric oxide synthase (NOS3 gene polymorphisms with respect to coronary artery disease (CAD have been published in the past two decades. However, their association with the disease, especially among different ethnic subgroups, still remains controversial. This prompted us to conduct a systematic review and an updated structured meta-analysis, which is the largest so far (89 articles, 132 separate studies, and a sample size of 69,235, examining association of three polymorphic forms of the NOS3 gene (i.e. Glu298Asp, T786-C and 27 bp VNTR b/a with CAD. In a subgroup analysis, we tested their association separately among published studies originating predominantly from European, Middle Eastern, Asian, Asian-Indian and African ancestries. The pooled analysis confirmed the association of all the three selected SNP with CAD in three different genetic models transcending all ancestries worldwide. The Glu298Asp polymorphism showed strongest association (OR range = 1.28-1.52, and P<0.00001 for all comparisons, followed by T786-C (OR range = 1.34-1.42, and P<0.00001 for all comparisons and 4b/a, (OR range = 1.19-1.41, and P ≤ 0.002 for all comparisons in our pooled analysis. Subgroup analysis revealed that Glu298Asp (OR range = 1.54-1.87, and P<0.004 for all comparisons and 4b/a (OR range = 1.71-3.02, and P<0.00001 for all comparisons have highest degree of association amongst the Middle Easterners. On the other hand, T786-C and its minor allele seem to carry a highest risk for CAD among subjects of Asian ancestry (OR range = 1.61-1.90, and P ≤ 0.01 for all comparisons.

  8. Gene polymorphisms and male infertility--a meta-analysis and literature review

    DEFF Research Database (Denmark)

    Tüttelmann, Frank; Rajpert-De Meyts, Ewa; Nieschlag, Eberhard

    2007-01-01

    (OR 1.81, 1.46-2.24 CI, PT (OR 1.39, 1.15-2.69 95% CI, P=0.0006) but not for POLG, DAZL, USP26 or FSHR. The influence of CAG repeat length in AR remains open and debated. Genes encoding nuclear proteins (PRM1/2, TNP1/2) and ER1 are possible candidates for further examination, while the role of TAF7L...

  9. Identification of genes highly downregulated in pancreatic cancer through a meta-analysis of microarray datasets: implications for discovery of novel tumor-suppressor genes and therapeutic targets.

    Science.gov (United States)

    Goonesekere, Nalin C W; Andersen, Wyatt; Smith, Alex; Wang, Xiaosheng

    2018-02-01

    The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a 5-year survival rate of about 7%. Recent failures of targeted therapies inhibiting kinase activity in clinical trials have highlighted the need for new approaches towards combating this deadly disease. In this study, we have identified genes that are significantly downregulated in PC, through a meta-analysis of large number of microarray datasets. We have used qRT-PCR to confirm the downregulation of selected genes in a panel of PC cell lines. This study has yielded several novel candidate tumor-suppressor genes (TSGs) including GNMT, CEL, PLA2G1B and SERPINI2. We highlight the role of GNMT, a methyl transferase associated with the methylation potential of the cell, and CEL, a lipase, as potential therapeutic targets. We have uncovered genetic links to risk factors associated with PC such as smoking and obesity. Genes important for patient survival and prognosis are also discussed, and we confirm the dysregulation of metabolic pathways previously observed in PC. While many of the genes downregulated in our dataset are associated with protein products normally produced by the pancreas for excretion, we have uncovered some genes whose downregulation appear to play a more causal role in PC. These genes will assist in providing a better understanding of the disease etiology of PC, and in the search for new therapeutic targets and biomarkers.

  10. ADRB3 Gene Trp64Arg Polymorphism and Essential Hypertension: A Meta-Analysis Including 9,555 Subjects.

    Science.gov (United States)

    Li, Yan-Yan; Lu, Xin-Zheng; Wang, Hui; Zhou, Yan-Hong; Yang, Xin-Xing; Geng, Hong-Yu; Gong, Ge; Kim, Hyun Jun

    2018-01-01

    Background: Presence of the β 3-Adrenergic receptor (ADRB3) gene Trp64Arg (T64A) polymorphism may be associated with an increased susceptibility for essential hypertension (EH). A clear consensus, however, has yet to be reached. Objective and methods: To further elucidate the relationship between the ADRB3 gene Trp64Arg polymorphism and EH, a meta-analysis of 9,555 subjects aggregated from 16 individual studies was performed. The combined odds ratios (ORs) and their corresponding 95% confidence intervals (CI) were evaluated using either a random or fixed effect model. Results: We found a marginally significant association between ADRB3 gene Trp64Arg polymorphism and EH in the whole population under the additive genetic model (OR: 1.200, 95% CI: 1.00-1.43, P = 0.049). Association within the Chinese subgroup, however, was significant under allelic (OR: 1.150, 95% CI: 1.002-1.320, P = 0.046), dominant (OR: 1.213, 95% CI: 1.005-1.464, P = 0.044), heterozygous (OR: 1.430, 95% CI:1.040-1.970, P = 0.03), and additive genetic models (OR: 1.280, 95% CI: 1.030-1.580, P = 0.02). A significant association was also found in the Caucasian subgroup under allelic (OR: 1.850, 95% CI: 1. 260-2.720, P = 0.002), dominant (OR: 2.004, 95% CI: 1.316-3.052, P = 0.001), heterozygous (OR: 2.220, 95% CI: 1.450-3.400, P = 0.0002), and additive genetic models (OR: 2.000, 95% CI: 1. 330-3.010, P = 0.0009). Conclusions: The presence of the ADRB3 gene Trp64Arg polymorphism is positively associated with EH, especially in the Chinese and Caucasian population. The Arg allele carriers of ADRB3 gene Trp64Arg polymorphism may be at an increased risk for developing EH.

  11. The Brassicaceae family displays divergent, shoot-skewed NLR resistance gene expression

    DEFF Research Database (Denmark)

    Munch, David; Gupta, Vikas; Bachmann, Asger

    2018-01-01

    Nucleotide-binding site leucine-rich repeat resistance genes (NLRs) allow plants to detect microbial effectors. We hypothesized that NLR expression patterns could reflect organ-specific differences in effector challenge and tested this by carrying out a meta-analysis of expression data for 1,235 ...

  12. Screening Key Genes Associated with the Development and Progression of Non-small Cell Lung Cancer Based on Gene-enrichment Analysis and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Wenwu HE

    2012-07-01

    Full Text Available Background and objective Non-small cell lung cancer (NSCLC is one of the most common malignant tumors; however, its causes are still not completely understood. This study was designed to screen the key genes and pathways related to NSCLC occurrence and development and to establish the scientific foundation for the genetic mechanisms and targeted therapy of NSCLC. Methods Both gene set-enrichment analysis (GSEA and meta-analysis (meta were used to screen the critical pathways and genes that might be corretacted with the development and progression of lung cancer at the transcription level. Results Using the GSEA and meta methods, focal adhesion and regulation of actin cytoskeleton were determined to be the more prominent overlapping significant pathways. In the focal adhesion pathway, 31 genes were statistically significant (P<0.05, whereas in the regulation of actin cytoskeleton pathway, 32 genes were statistically significant (P<0.05. Conclusion The focal adhesion and the regulation of actin cytoskeleton pathways might play important roles in the occurrence and development of NSCLC. Further studies are needed to determine the biological function for the positiue genes.

  13. Survivin protein expression is involved in the progression of non-small cell lung cancer in Asians: a meta-analysis

    International Nuclear Information System (INIS)

    Duan, Liang; Hu, Xuefei; Jin, Yuxing; Liu, Ruijun; You, Qingjun

    2016-01-01

    Surviving expression might serve as a prognostic biomarker predicting the clinical outcome of non-small cell lung cancer (NSCLC). The study was conducted to explore the potential correlation of survivin protein expression with NSCLC and its clinicopathologic characteristics. PubMed, Medline, Cochrane Library, CNKI and Wanfang database were searched through January 2016 with a set of inclusion and exclusion criteria. Data was extracted from these articles and all statistical analysis was conducted by using Stata 12.0. A total of 28 literatures (14 studies in Chinese and 14 studies in English) were enrolled in this meta-analysis, including 3206 NSCLC patients and 816 normal controls. The result of meta-analysis demonstrated a significant difference of survivin positive expression between NSCLC patients and normal controls (RR = 7.16, 95 % CI = 4.63-11.07, P < 0.001). To investigate the relationship of survivin expression and clinicopathologic characteristics, we performed a meta-analysis in NSCLC patients. Our results indicates survivin expression was associated with histological differentiation, tumor-node-metastasis (TNM) stage and lymph node metastasis (LNM) (RR = 0.80, 95 % CI = 0.73-0.87, P < 0.001; RR = 0.75, 95 % CI = 0.67-0.84, P < 0.001; RR = 1.14, 95 % CI = 1.01-1.29, P = 0.035, respectively), but not pathological type and tumor size. (RR = 1.00, 95 % CI = 0.93-1.07, P = 0.983; RR = 0.95, 95 % CI = 0.86-1.05, P = 0.336, respectively). Higher expression of survivin in NSCLC patients was found when compared to normal controls. Survivin expression was associated with the clinicopathologic characteristics of NSCLC and may serves as an important biomarker for NSCLC progression

  14. Gene Expression Commons: an open platform for absolute gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Jun Seita

    Full Text Available Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000 of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through meta-analysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford.edu/ which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples.

  15. A Meta-analysis on the correlation between the polymorphism of angiotensin converting enzyme gene and hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ling CHEN

    2014-01-01

    Full Text Available Objective To systematically investigate the correlation between the polymorphism of angiotensin converting enzyme (ACE gene I/D and hypertrophic cardiomyopathy. Methods The databases, such as PubMed, Embase, OVID, Web of Science, Cochrane library, CNKI, WanFang Data and VIP, were searched to collect the studies on the correlation between ACE I/D polymorphism and hypertrophic cardiomyopathy susceptibility. Studies that met the inclusion criteria were Meta-analyzed using Stata 11.0 software. Results Fifteen articles were collected including 1114 cases and 1648 controls. The Meta-analysis indicated that there was significant correlation between the 4 models of ACE I/D polymorphism and hypertrophic cardiomyopathy susceptibility [D vs I: OR=1.49, 95%CI (1.20, 1.84; DD vs (ID+II: OR=1.56, 95%CI (1.17, 2.08; (DD+ID vs II: OR=1.76, 95%CI (1.30, 2.38; DD vs II: OR=2.20, 95%CI (1.44, 3.37]. In subgroup analysis, the significant difference existed in Asian population, but no significance was found in European population (P<0.05. Conclusions There is a positive correlation between hypertrophic cardiomyopathy and ACE I/D polymorphism in population, and D allele and DD genotype are likely to be the risk factors of hypertrophic cardiomyopathy. But such correlation does not exist in European population. DOI: 10.11855/j.issn.0577-7402.2013.12.07

  16. Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis.

    Science.gov (United States)

    Wu, Shuai; Han, Yan; Hu, Qiang; Zhang, Xiaojie; Cui, Guangcheng; Li, Zezhi; Guan, Yangtai

    2017-05-01

    Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T and ACE I/D polymorphisms and DPN found in various types of electronic databases. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) quality score systems were used to determine the quality of the articles selected for inclusion. Odds ratios (ORs) and its corresponding 95 % confidence interval (95 % CI) were calculated. We used STATA statistical software (version 12.0, Stata Corporation, College Station, TX, USA) to deal with statistical data. Our results indicated an association of ACE D>I mutation (OR = 1.43, 95 % CI 1.12-1.83, P = 0.004) and MTHFR 677 C>T mutation (OR = 1.43, 95 % CI 1.08-1.90, P = 0.014) with DPN under the allele model, and similar results were also found under the dominant model (all P T polymorphism may be the main risk factor for DPN in Turkey under four genetic models. ACE D>I mutation was correlated with DPN in Japanese and Pakistani populations in the majority of groups. The relationships of MTHFR 677 C>T and ACE I/D polymorphisms with DPN patients presented in this meta-analyses support the view that the MTHFR and ACE genes might play an important role in the development of DPN.

  17. The catalase C-262T gene polymorphism and cancer risk: a systematic review and meta-analysis.

    Science.gov (United States)

    Shen, Yongchun; Li, Diandian; Tian, Panwen; Shen, Konglong; Zhu, Jing; Feng, Mei; Wan, Chun; Yang, Ting; Chen, Lei; Wen, Fuqiang

    2015-04-01

    Many studies suggest that catalase C-262T gene polymorphism is associated with cancer risk, but with inconsistent results. This study aimed to summarize the overall association between catalase C-262T polymorphism and cancer risk. Literature search was performed in PubMed, Embase, and other databases, studies regarding the association between catalase C-262T polymorphism and cancer risk were identified, and data were retrieved and analyzed by using Review Manager 5.0.24 and STATA 12.0. A total of 18 publications with 22 case-control studies, including 9777 cancer patients and 12,223 controls, met the inclusion criteria. Meta-analysis results showed significant association between catalase C-262 T polymorphism and cancer risk (TT vs CT + CC: odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.03-1.31, P = 0.01). Subgroup analyses stratified by cancer types suggested the catalase C-262T polymorphism was significantly associated with an increased prostate cancer risk (TT vs CT + CC: OR = 1.61, 95% CI = 1.17-2.22, P = 0.004); for subgroup analyses stratified by ethnicity, no associations between this polymorphism and Asians or whites were identified (CT + TT vs CC: OR = 1.11, 95% CI = 0.98-1.26, P = 0.09 for whites; OR = 1.19, 95% CI = 0.78-1.80, P = 0.42 for Asians). In summary, the catalase C-262T polymorphism may be a risk factor for cancer with cancer type-specific effects. Further studies should be performed to confirm these findings.

  18. Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

    International Nuclear Information System (INIS)

    Dong, Lihua; Cui, Jingkun; Tang, Fengjiao; Cong, Xiaofeng; Han, Fujun

    2015-01-01

    Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATM polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was

  19. Association of vitamin D receptor gene polymorphisms with susceptibility to childhood asthma: A meta-analysis.

    Science.gov (United States)

    Zhao, Dong-Dong; Yu, Dan-Dan; Ren, Qiong-Qiong; Dong, Bao; Zhao, Feng; Sun, Ye-Huan

    2017-04-01

    As for the association of vitamin D receptor (VDR) gene polymorphisms with susceptibility to pediatric asthma, results of published studies yielded conflicts. A systematic review was conducted on the relationship between childhood asthma and VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236). PubMed, Web of Science, CBM (Chinese Biomedical Database), CNKI (China National Knowledge Infrastructure), and Wanfang (Chinese) database were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated. Overall results suggested that there was a statistically significant association between ApaI polymorphism and childhood asthma in homozygote model (OR = 1.674, 95%CI = 1.269-2.208, P childhood asthma in the homozygote (OR = 1.462, 95%CI = 1.016-2.105, P = 0.041) and allele models (OR = 1.181, 95%CI = 1.006-1.386, P = 0.042). This association reached significance only in the Caucasian group (OR = 1.236, 95%CI = 1.029-1.485, P = 0.023). For FokI, a statistical association was detected in dominant model (OR = 1.281, 95%CI = 1.055-1.555, P = 0.012); this association was significant in allele model (OR = 1.591, 95%CI = 1.052-2.405, P = 0.028) in Caucasian. ApaI polymorphism plays a particular role in childhood asthma in Asians. FokI polymorphism may be connected with pediatric asthma in Caucasian population. And BsmI polymorphism marginally contributes to childhood asthma susceptibility, while there might be no association between TaqI polymorphism and childhood asthma risk. Pediatr Pulmonol. 2017;52:423-429. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. A meta-analysis of the association of CKM gene rs8111989 polymorphism with sport performance

    Directory of Open Access Journals (Sweden)

    Chunyang Chen

    2017-12-01

    Full Text Available The muscle-specific creatine kinase (CKM A/G variants (rs8111989 have been associated with skeletal muscle performance in humans; they are correlated with physical performance and contribute to differences in the maximum oxygen uptake (VO2max responses during power or endurance training. However, there is not enough definitive evidence to demonstrate whether the A and G allelic variants of the CKM gene rs8111989 are indeed genetic factors that can influence human physical performance. In our study, we identified 9 articles on CKM in a literature search, and conducted two meta-analyses on the CKM rs8111989 A/G allele or genotype differences between power or endurance athletes and general controls. We found that the power athletes had a significantly higher frequency of the G allele (OR, 1.14; 95% CI, 1.02-1.28, P=0.03 and GG genotype (OR, 1.54; 95% CI, 1.24-1.91, P<0.0001 compared to controls, but there was no significant difference for the endurance athletes (G allele, OR, 0.95, 95%CI, 0.85-1.06, P=0.34; GG genotype, OR, 1.00, 95%CI, 0.78-1.27, P=1.00. The results provide additional evidence to support the notion that human physical performance might be influenced by genetic profiles, especially in power sports.

  1. A meta-analysis of the association of CKM gene rs8111989 polymorphism with sport performance.

    Science.gov (United States)

    Chen, Chunyang; Sun, Yan; Liang, Hao; Yu, Dan; Hu, Songnian

    2017-12-01

    The muscle-specific creatine kinase (CKM) A/G variants (rs8111989) have been associated with skeletal muscle performance in humans; they are correlated with physical performance and contribute to differences in the maximum oxygen uptake (VO 2 max) responses during power or endurance training. However, there is not enough definitive evidence to demonstrate whether the A and G allelic variants of the CKM gene rs8111989 are indeed genetic factors that can influence human physical performance. In our study, we identified 9 articles on CKM in a literature search, and conducted two meta-analyses on the CKM rs8111989 A/G allele or genotype differences between power or endurance athletes and general controls. We found that the power athletes had a significantly higher frequency of the G allele (OR, 1.14; 95% CI, 1.02-1.28, P=0.03) and GG genotype (OR, 1.54; 95% CI, 1.24-1.91, Pathletes (G allele, OR, 0.95, 95%CI, 0.85-1.06, P=0.34; GG genotype, OR, 1.00, 95%CI, 0.78-1.27, P=1.00). The results provide additional evidence to support the notion that human physical performance might be influenced by genetic profiles, especially in power sports.

  2. Discs Large Homolog 5 (DLG5 Gene Polymorphism and Crohn’s Disease: A Meta-Analysis of the Published Studies

    Directory of Open Access Journals (Sweden)

    Arezoo Shafieyoun

    2016-05-01

    Full Text Available The real pathophysiology of Crohn’s disease is unknown. The higher prevalence of Crohn’s disease in Caucasian and Jewish ethnicities, as well as its familial aggregation and higher concordance among monozygotic twins, suggest some roles for genes in its development, clinical progression, and outcome. Recent original studies have indicated DLG5113G/A gene polymorphism as a risk factor for Crohn’s disease. Meanwhile, the results of these studies are not consistent. We performed the current meta-analysis to understand whether there is any association between DLG5 gene polymorphism and the risk of Crohn’s disease. PubMed was searched to find the case-control studies on DLG5 gene polymorphisms and Crohn’s disease. This search compiled 65 articles and based on our criteria. 11 articles were included in this meta-analysis. The association between the DLG5 113G/A polymorphism and the risk of disease was assessed using odds ratio (OR and 95% confidence interval (95% CI. Heterogeneity was evaluated based on I2 values.  Random and fixed-effect models were used when I2>50% and I2≤50%, respectively. Eleven studies with a total of 4648 cases and 5677 controls were pooled. Based on our meta-analysis, DLG5113G/A gene polymorphism both at genotypic and allelic levels were not associated with the risk of Crohn’s disease. Pooled data indicated no significant association between DLG5113G/A gene polymorphism and the development of Crohn’s disease. In order to achieve a superior conclusion, multicenter studies on larger number of patients are recommended.

  3. Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.

    Directory of Open Access Journals (Sweden)

    Clara C Elbers

    Full Text Available Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC and low-density lipoprotein cholesterol (LDL-C (p = 8.8×10(-7 and p = 1.5×10(-6 respectively and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C levels (p = 13.5×10(-12. The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.

  4. Meta-analysis of the effect of overexpression of CBF/DREB family genes on drought stress response

    Science.gov (United States)

    Transcription factors C-repeat/dehydration-responsive element binding proteins (CBF/DREB) play an important role in plant response to abiotic stresses. Over-expression of various CBF/DREB genes in diverse plants have been reported, but inconsistency of gene donor, recipient genus, parameters used i...

  5. Interleukin 1 beta gene and risk of schizophrenia: detailed case-control and family-based studies and an updated meta-analysis.

    Science.gov (United States)

    Shibuya, Masako; Watanabe, Yuichiro; Nunokawa, Ayako; Egawa, Jun; Kaneko, Naoshi; Igeta, Hirofumi; Someya, Toshiyuki

    2014-01-01

    Interleukin-1 beta (IL-1β) has been implicated in the pathophysiology of schizophrenia. To assess whether the IL1B gene confers increased susceptibility to schizophrenia, we conducted case-control and family-based studies and an updated meta-analysis. We tested the association between IL1B and schizophrenia in 1229 case-control and 112 trio samples using 12 markers, including common tagging single nucleotide variations (SNVs) and a rare non-synonymous variation detected by resequencing the coding regions. We also performed a meta-analysis of rs16944 using a total of 8724 case-control and 201 trio samples from 16 independent populations. We found no significant associations between any of the 12 SNVs examined and schizophrenia in either case-control or trio samples. Moreover, our meta-analysis results showed no significant association between the common SNV, rs16944, and schizophrenia. The present study does not support a role for IL1B in schizophrenia susceptibility.

  6. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism

    DEFF Research Database (Denmark)

    Sapkota, Yadav; Steinthorsdottir, Valgerdur; Morris, Andrew P.

    2017-01-01

    Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endomet...

  7. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

    NARCIS (Netherlands)

    Fan, Q.; Verhoeven, V.J.; Wojciechowski, R.; Barathi, V.A.; Hysi, P.G.; Guggenheim, J.A.; Hohn, R.; Vitart, V.; Khawaja, A.P.; Yamashiro, K.; Hosseini, S.M.; Lehtimaki, T.; Lu, Y.; Haller, T.; Xie, J.; Delcourt, C; Pirastu, M.; Wedenoja, J.; Gharahkhani, P.; Venturini, C.; Miyake, M.; Hewitt, A.W.; Guo, X.; Mazur, J.; Huffman, J.E.; Williams, K.M.; Polasek, O.; Campbell, H.; Rudan, I.; Vatavuk, Z.; Wilson, J.F.; Joshi, P.K.; McMahon, G.; St Pourcain, B.; Evans, D.M.; Simpson, C.L.; Schwantes-An, T.H.; Igo, R.P., Jr.; Mirshahi, A.; Cougnard-Gregoire, A.; Bellenguez, C.; Blettner, M.; Raitakari, O.; Kahonen, M.; Seppala, I.; Zeller, T.; Meitinger, T.; Ried, J.S.; Gieger, C.; Portas, L.; Leeuwen, E.M. van; Amin, N.; Uitterlinden, A.G.; Rivadeneira, F.; Hofman, A.; Vingerling, J.R.; Wang, Y.X.; Wang, X.; Boh, E.T.H.; Ikram, M.K.; Sabanayagam, C.; Gupta, P.; Tan, V.; Zhou, L; Ho, C.E.; Lim, W.; Beuerman, R.W.; Siantar, R.; Tai, E.S.; Vithana, E.; Mihailov, E.; Khor, C.C.; Hayward, C.; Luben, R.N.; Foster, P.J.; Klein, B.E.; Klein, R.; Wong, H.S.; Mitchell, P.; Metspalu, A.; Aung, T.; Young, T.L.; He, M.; Parssinen, O.; Duijn, C.M. van; Wang, J.J.; Williams, C.; Jonas, J.B.; Teo, Y.Y.; Mackey, D.A.; Oexle, K.; Yoshimura, N.; Paterson, A.D.; Pfeiffer, N.; Wong, T.Y.; Baird, P.N.; Stambolian, D.; Wilson, J.E.; Cheng, C.Y.; Hammond, C.J.; Klaver, C.C.W.; et al.,

    2016-01-01

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main

  8. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

    NARCIS (Netherlands)

    Q. Fan (Qiao); V.J.M. Verhoeven (Virginie); R. Wojciechowski (Robert); V.A. Barathi (Veluchamy); P.G. Hysi (Pirro); J. Guggenheim (Jean); R. Höhn (René); V. Vitart (Veronique); A.P. Khawaja (Anthony P.); K. Yamashiro (Kenji); S.M. Hosseini (S Mohsen); T. Lehtimäki (Terho); Y. Lu (Yi); T. Haller (Toomas); J. Xie (Jing); C. Delcourt (Cécile); M. Pirastu (Mario); J. Wedenoja (Juho); P. Gharahkhani (Puya); C. Venturini (Cristina); M. Miyake (Masahiro); A.W. Hewit (Alex); X. Guo (Xiaobo); J. Mazur (Johanna); J.E. Huffman (Jenifer E.); K.M. Williams (Katie M.); O. Polasek (Ozren); H. Campbell (Harry); I. Rudan (Igor); Z. Vatavuk (Zoran); J.F. Wilson (James F); P.K. Joshi (Peter); G. Mcmahon (George); B. St Pourcain (Beate); D.M. Evans (David); C.L. Simpson (Claire); T.-H. Schwantes-An (Tae-Hwi); R.P. Igo Jr. (Robert); A. Mirshahi (Alireza); A. Cougnard-Grégoire (Audrey); C. Bellenguez (Céline); M. Blettner (Maria); O. Raitakari (Olli); M. Kähönen (Mika); I. Seppälä (Ilkka); T. Zeller (Tanja); T. Meitinger (Thomas); J.S. Ried (Janina); C. Gieger (Christian); L. Portas (Laura); E.M. van Leeuwen (Elisa); N. Amin (Najaf); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); A. Hofman (Albert); J.R. Vingerling (Hans); Y. Wang (Ying); X. Wang (Xu); E. Tai-Hui Boh (Eileen); M.K. Ikram (Kamran); C. Sabanayagam (Charumathi); P. Gupta (Preeti); V. Tan (Vincent); L. Zhou (Lei); C.E.H. Ho (Candice E. H.); W. Lim (Wan'E); R.W. Beuerman (Roger W.); R. Siantar (Rosalynn); E.-S. Tai (E-Shyong); E.N. Vithana (Eranga); E. Mihailov (Evelin); C.C. Khor; C. Hayward (Caroline); R.N. Luben (Robert); P.J. Foster (Paul); B.E.K. Klein (Barbara); R. Klein (Ronald); H.-S. Wong (Hoi-Suen); P. Mitchell (Paul); A. Metspalu (Andres); T. Aung (Tin); T.L. Young (Terri L.); M. He (Mingguang); O. Pärssinen (Olavi); C.M. van Duijn (Cornelia); J. Jin Wang (Jie); C. Williams (Cathy); J.B. Jonas (Jost B.); Y.Y. Teo (Yik Ying); D.A. Mackey (David); K. Oexle (Konrad); N. Yoshimura; A.D. Paterson (Andrew D.); N. Pfeiffer (Norbert); T.Y. Wong (Tien Yin); P.N. Baird (Paul); D. Stambolian (Dwight); J.E.B. Wilson (Joan E. Bailey); C-Y. Cheng (Ching-Yu); C.J. Hammond (Christopher J.); C.C.W. Klaver (Caroline); S-M. Saw (Seang-Mei); J.S. Rahi (Jugnoo); J.-F. Korobelnik (Jean-François); J.P. Kemp (John); N.J. Timpson (Nicholas); G.D. Smith; J.E. Craig (Jamie E.); K.P. Burdon (Kathryn P.); R. Fogarty (Rhys); S.K. Iyengar (Sudha); E.Y. Chew (Emily); S. Janmahasatian (Sarayut); N.G. Martin (Nicholas); S. MacGregor (Stuart); L. Xu (Liang); M. Schache (Maria); M. Nangia (Monika); S. Panda-Jonas (Songhomitra); A.F. Wright (Alan); J.R. Fondran (Jeremy R.); J.H. Lass (Jonathan H.); S. Feng (Sheng); J.H. Zhao (Jing Hua); K.T. Khaw; N.J. Wareham (Nick); T. Rantanen (Taina); J. Kaprio (Jaakko); C.P. Pang (Chi Pui); L.J. Chen (Li Jia); P.O. Tam (Pancy O.); V. Jhanji (Vishal); A.L. Young (Alvin L.); A. Döring (Angela); L.J. Raffel (Leslie); M.-F. Cotch (Mary-Frances); X. Li (Xiaohui); S.P. Yip (Shea Ping); M.K.H. Yap (Maurice K.H.); G. Biino (Ginevra); S. Vaccargiu (Simona); M. Fossarello (Maurizio); B. Fleck (Brian); S. Yazar (Seyhan); J.W.L. Tideman (J. Willem L.); M. Tedja (Milly); T. Léveillard (Thierry); M.A. Morrison (Margaux A.); L.A. Farrer (Lindsay); X. Zhou (Xiangtian); W. Chen (Wei); N. Mizuki (Nobuhisa); A. Meguro (Akira); K.M. Makela (Kari Matti)

    2016-01-01

    textabstractMyopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism

  9. Analysis of baseline gene expression levels from ...

    Science.gov (United States)

    The use of gene expression profiling to predict chemical mode of action would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies has yielded useful information on baseline fluctuations in gene expression. A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selectiv

  10. Association of three common single nucleotide polymorphisms of ATP binding cassette G8 gene with gallstone disease: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhao-Yan Jiang

    Full Text Available In this study, we evaluated the association between these polymorphisms and gallstone disease using meta-analysis and compared the hepatic ABCG5/G8 mRNA expression and biliary lipids composition in patients with different genotypes of T400K and Y54C.Data were analyzed using the Stata/SE 11.0 software and a random- effects model was applied irrespective of between-study heterogeneity. Hepatic mRNA expression of ABCG5/G8 genes in 182 patients with gallstone disease and 35 gallstone-free patients who underwent cholecystectomy were determined using real-time PCR. Genotypes of Y54C and T400K in the ABCG8 gene were determined by allelic discrimination using either genomic DNA or hepatic cDNA as template by Taqman assays. Biliary compostion in gallbladder bile was assayed in these patients as well.Ten papers including 13 cohorts were included for the final analysis. In the genotype model, the overall association between genotype with gallstone was significant for D19H (OR = 2.43, 95%CI: 2.23-2.64, P<0.001, and for Y54C (OR = 1.36, 95%CI: 1.01-1.83, P = 0.044, or T400K (OR = 1.17, 95%CI: 0.96-1.43. P = 0.110. In allele model, minor alleles of D19H polymorphism (allele D: OR = 2.25, 95%CI: 2.10-2.42, P<0.001 and of T400K polymorphism (allele K: OR = 1.18, 95%CI: 1.06-1.31, P<0.001 were related with an increased risk of gallstone disease. However, minor allele of Y54C polymorphism (allele Y, OR = 1.08, 95%CI: 0.96-1.21, P = 0.146 was not related with gallstone disease. I(2 statistics indicated no significant between-study heterogeneity for all genetic models for any of the three polymorphisms. Funnel plot and Egger's test suggested the absence of publication bias as well. However, no association of T400K and Y54C polymorphism with hepatic ABCG8/G5 mRNA expression or biliary lipids composition was found.Our study showed strong association of D19H polymorphism with gallstone disease. T400K and Y54C polymorphism, though to

  11. Meta-analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

    OpenAIRE

    Wen-Ying Fan; Ning-Pu Liu

    2015-01-01

    AIM:To collectively evaluate the association of intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism (rs5498) with diabetic retinopathy (DR) in patients with type 2 diabetic mellitus (T2DM).METHODS:Overall review of available literatures relating K469E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios (ORs). Potential sources of heterogeneity and bias were explored.RESULTS:Seven studi...

  12. Consistent Differential Expression Pattern (CDEP) on microarray to identify genes related to metastatic behavior.

    Science.gov (United States)

    Tsoi, Lam C; Qin, Tingting; Slate, Elizabeth H; Zheng, W Jim

    2011-11-11

    To utilize the large volume of gene expression information generated from different microarray experiments, several meta-analysis techniques have been developed. Despite these efforts, there remain significant challenges to effectively increasing the statistical power and decreasing the Type I error rate while pooling the heterogeneous datasets from public resources. The objective of this study is to develop a novel meta-analysis approach, Consistent Differential Expression Pattern (CDEP), to identify genes with common differential expression patterns across different datasets. We combined False Discovery Rate (FDR) estimation and the non-parametric RankProd approach to estimate the Type I error rate in each microarray dataset of the meta-analysis. These Type I error rates from all datasets were then used to identify genes with common differential expression patterns. Our simulation study showed that CDEP achieved higher statistical power and maintained low Type I error rate when compared with two recently proposed meta-analysis approaches. We applied CDEP to analyze microarray data from different laboratories that compared transcription profiles between metastatic and primary cancer of different types. Many genes identified as differentially expressed consistently across different cancer types are in pathways related to metastatic behavior, such as ECM-receptor interaction, focal adhesion, and blood vessel development. We also identified novel genes such as AMIGO2, Gem, and CXCL11 that have not been shown to associate with, but may play roles in, metastasis. CDEP is a flexible approach that borrows information from each dataset in a meta-analysis in order to identify genes being differentially expressed consistently. We have shown that CDEP can gain higher statistical power than other existing approaches under a variety of settings considered in the simulation study, suggesting its robustness and insensitivity to data variation commonly associated with microarray

  13. Microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease: A comprehensive meta-analysis

    OpenAIRE

    LI, HUI; FU, WEI-PING; HONG, ZE-HUI

    2012-01-01

    Microsomal epoxide hydrolase (EPHX1) is an enzyme involved in the detoxification the products of smoking and is proposed to be a genetic factor for the development of chronic obstructive pulmonary disease (COPD). Two functional polymorphisms of EPHX1, T113C and A139G, have been analyzed in numerous studies to assess the COPD risk attributed to these variants. However, the conclusions were controversial. We performed a comprehensive meta-analysis to clarify these findings. A total of 24 studie...

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

    Directory of Open Access Journals (Sweden)

    Liyuan Han

    2014-01-01

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

  15. Evaluation and identification of factors related to KRAS and BRAF gene mutations in colorectal cancer: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Li Lin

    2016-01-01

    Conclusion: The meta-analysis reveals that KRAS has a slightly higher mutation rate in MSI-L/MSS tumors. Moreover, BRAF mutations have higher detection rates in right-sided colorectal cancer, which suggests that BRAF mutations are likely in CIMP-H tumors. Therefore, based on these findings, the molecular diagnostic tests to be conducted in colorectal cancer patients can be determined according to the location/clinical features of the tumor.

  16. Role of TNF-α -308G/A gene polymorphism in gastric cancer risk: A case control study and meta-analysis.

    Science.gov (United States)

    Du, Li Chuan; Gao, Ru

    2017-07-01

    In the Chinese population, gastric cancer (GC) is ranked as the third most common type of cancer. Although the exact etiology of GC development is unclear, several factors, including genetic and environmental, have been identified as risk factors. Variations in cytokine genes and their receptors have been related to a higher risk of GC. A single nucleotide polymorphism in the promoter region of tumor necrosis factor-α (TNF-α) (-308G>A) has been associated with a higher risk of GC and in the present study we evaluated its possible association with GC in a Chinese cohort. In addition, we performed a meta-analysis to draw a firm conclusion about the association between TNF-α gene polymorphisms and GC. We enrolled 400 Chinese GC patients and matched healthy controls hailing from similar geographical areas. The TNF-α -308G/A polymorphism was genotyped by allele-specific polymerase chain reaction (AS-PCR). For the meta-analysis, earlier published articles were searched and eligible studies were included. Prevalence of the heterozygous mutant (GA) and minor allele (A) were significantly higher in GC cases compared to healthy controls (GA: pA) with susceptibility to GC was only found in the Caucasian population (A vs G: p=0.001; AA vs GG: p=0.01; AG vs GG: p<0.0001; AA vs AG+GG: p=0.01; AA+AG vs p=0.003). The results of the present case control study and meta-analysis showed that associations between TNF-a variants with susceptibility to GC development is population and ethnic specific.

  17. Association between C677T and A1298C polymorphisms of the MTHFR gene and risk of male infertility: a meta-analysis.

    Science.gov (United States)

    Yang, Y; Luo, Y Y; Wu, S; Tang, Y D; Rao, X D; Xiong, L; Tan, M; Deng, M Z; Liu, H

    2016-04-26

    Published studies on the association between the C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene and male infertility risk are controversial. To obtain a more precise evaluation, we performed a meta-analysis based on published case-control studies. We conducted an electronic search of PubMed, EMBASE, the Cochrane Library, the Web of Science, and the China Knowledge Resource Integrated Database for papers on MTHFR gene C677T and A1298C polymorphisms and male infertility risk. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were used to assess the strength of association in homozygote, heterozygote, dominant, recessive, and additive models. Statistical heterogeneity, test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 13.0). Overall, 21 studies of C677T (4505 cases and 4024 controls) and 13 studies of A1298C (2785 cases and 3094 controls) were included in this meta-analysis. For C677T, the homozygote comparison results were OR = 1.629, 95%CI (1.215- 2.184), and the recessive model results were OR = 1.462 (1.155- 1.850). For A1298C, the homozygote comparison results were OR = 1.289 (1.029-1.616), and the recessive model results were OR = 1.288 (1.034-1.604). In conclusion, the current meta-analysis showed that the MTHFR C677T polymorphism was associated with a significantly increased male infertility risk in the Asian and overall populations, but not in the Caucasian population, and there was a significant association between the A1298C polymorphism and male infertility risk in the Asian, Caucasian, and overall groups.

  18. Gene Expression Omnibus (GEO)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  19. State-related alterations of gene expression in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Berk, Michael

    2012-01-01

    Munkholm K, Vinberg M, Berk M, Kessing LV. State-related alterations of gene expression in bipolar disorder: a systematic review. Bipolar Disord 2012: 14: 684-696. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective:  Alterations in gene expression in bipolar disorder...... have been found in numerous studies. It is unclear whether such alterations are related to specific mood states. As a biphasic disorder, mood state-related alterations in gene expression have the potential to point to markers of disease activity, and trait-related alterations might indicate...... vulnerability pathways. This review therefore evaluated the evidence for whether gene expression in bipolar disorder is state or trait related. Methods:  A systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline for reporting systematic reviews, based...

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

    Science.gov (United States)

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

    2017-08-01

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

  1. Longitudinal Meta-analysis

    NARCIS (Netherlands)

    Hox, J.J.; Maas, C.J.M.; Lensvelt-Mulders, G.J.L.M.

    2004-01-01

    The goal of meta-analysis is to integrate the research results of a number of studies on a specific topic. Characteristic for meta-analysis is that in general only the summary statistics of the studies are used and not the original data. When the published research results to be integrated

  2. Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets

    Directory of Open Access Journals (Sweden)

    Max Lam

    2017-11-01

    Full Text Available Here, we present a large (n = 107,207 genome-wide association study (GWAS of general cognitive ability (“g”, further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum. Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.

  3. ACE I/D Gene Polymorphism Can't Predict the Steroid Responsiveness in Asian Children with Idiopathic Nephrotic Syndrome: A Meta-Analysis

    Science.gov (United States)

    Su, Li-Na; Lei, Feng-Ying; Huang, Wei-Fang; Zhao, Yan-Jun

    2011-01-01

    Background The results from the published studies on the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the treatment response to steroid in Asian children with idiopathic nephrotic syndrome (INS) is still conflicting. This meta-analysis was performed to evaluate the relation between ACE I/D gene polymorphism and treatment response to steroid in Asian children and to explore whether ACE D allele or DD genotype could become a predictive marker for steroid responsiveness. Methodology/Principal Findings Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2010, and eligible investigations were synthesized using meta-analysis method. Five investigations were identified for the analysis of association between ACE I/D gene polymorphism and steroid-resistant nephrotic syndrome (SRNS) risk in Asian children and seven studies were included to explore the relationship between ACE I/D gene polymorphism and steroid-sensitive nephrotic syndrome (SSNS) susceptibility. Five investigations were recruited to explore the difference of ACE I/D gene distribution between SRNS and SSNS. There was no a markedly association between D allele or DD genotype and SRNS susceptibility or SSNS risk, and the gene distribution differences of ACE between SRNS and SSNS were not statistically significant. II genotype might play a positive role against SRNS onset but not for SSNS (OR = 0.51, P = 0.02; OR = 0.95, P = 0.85; respectively), however, the result for the association of II genotype with SRNS risk was not stable. Conclusions/Significance Our results indicate that D allele or DD homozygous can't become a significant genetic molecular marker to predict the treatment response to steroid in Asian children with INS. PMID:21611163

  4. Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis.

    Science.gov (United States)

    Zhu, Ming; Zhang, Jie; Nie, Shaofa; Yan, Weirong

    2012-09-01

    There have been many studies concerning the associations of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T polymorphisms with pregnancy induced hypertension (PIH) among Chinese populations. However, the results were inconsistent, prompting the necessity of meta-analysis. Studies published in English and Chinese were mainly searched in EMbase, PubMed and CBM up to January 2012. Twenty-three studies with 3,551 subjects for ACE I/D and seven studies with 1,296 subjects for AGT M235T were included. Significant associations were found between ACE I/D and PIH under dominant, recessive and allelic models. A separate analysis confined to preeclampsia suggested that ACE I/D was associated with preeclampsia under recessive model and allelic model, but not dominant model. Stratified analyses were conducted as meta-regression analysis indicated that the sample size of case group was a significant source of heterogeneity, which suggested no significant association between ACE I/D and PIH in the subgroup of more than 100 cases. Associations were found between AGT M235T and PIH under dominant genetic model (OR = 1.59; 95 %CI: 1.04-2.42), recessive genetic model (OR = 1.60; 95 %CI: 1.07-2.40), and allelic model (OR = 1.40; 95 %CI: 1.17-1.68). No publication bias was found in either meta-analysis. The present meta-analysis suggested significant associations between ACE I/D, AGT M235T and PIH in Chinese populations. However, no significant association was found between ACE I/D and PIH in the subgroup of more than 100 cases. Studies with larger sample sizes are necessary to investigate the associations between gene polymorphisms and PIH in Chinese populations.

  5. Association of rs2228570 polymorphism of vitamin D receptor gene with degenerative disc disease: a meta-analysis involving 2947 subjects.

    Science.gov (United States)

    Zong, Qiang; Ni, Dongkui; Li, Lijun; Shi, Yubo

    2015-01-01

    This study aimed to explore the association between the rs2228570 polymorphism in the vitamin D receptor gene and degenerative disc disease (IDD), especially in European. We perform a meta-analysis to analyze the association after searching the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed, Medline and EMBASE databases. And odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. A total of 10 studies involving 1,465 cases and 1,482 controls were included in the meta-analysis. Overall, there was not significant risk between rs2228570 polymorphism and degenerative disc disease in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by others indicates an association between IDD and the FF genotype (OR=0.62, 95% CI=0.43- 0.90, P=0.486) in age =40, and the F allele (OR=0.84, 95% CI=0.73-0.96, P=0.992), FF genotype (OR=0.78, 95% CI=0.65-0.93, P=0.853) in sample size > 300, and ff genotype (OR=0.91, 95% CI=1.11-3.29, P=0.783), FF genotype (OR=0.70, 95% CI=0.51-0.96, P=0.258) in Northern European. This meta-analysis suggested that the rs2228570 polymorphism may not be associated with degenerative disc disease. However, there existed some diversities, especially in age 300, countries in Northern Europe, suggesting that carrying the VDR FokI F allele may be a protective factor against IDD development. But a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease.

  6. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence.

    Science.gov (United States)

    Sniekers, Suzanne; Stringer, Sven; Watanabe, Kyoko; Jansen, Philip R; Coleman, Jonathan R I; Krapohl, Eva; Taskesen, Erdogan; Hammerschlag, Anke R; Okbay, Aysu; Zabaneh, Delilah; Amin, Najaf; Breen, Gerome; Cesarini, David; Chabris, Christopher F; Iacono, William G; Ikram, M Arfan; Johannesson, Magnus; Koellinger, Philipp; Lee, James J; Magnusson, Patrik K E; McGue, Matt; Miller, Mike B; Ollier, William E R; Payton, Antony; Pendleton, Neil; Plomin, Robert; Rietveld, Cornelius A; Tiemeier, Henning; van Duijn, Cornelia M; Posthuma, Danielle

    2017-07-01

    Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (r g = 0.89, LD score regression P = 5.4 × 10 -29 ). These findings provide new insight into the genetic architecture of intelligence.

  7. The association between the polymorphism rs2231142 in the ABCG2 gene and gout risk: a meta-analysis.

    Science.gov (United States)

    Lv, Xiaofei; Zhang, Yuan; Zeng, Fangfang; Yin, Aihua; Ye, Ning; Ouyang, Haimei; Feng, Dan; Li, Dan; Ling, Wenhua; Zhang, Xiaozhuang

    2014-12-01

    Gout is a common metabolic disorder with high heritability. We tried to explore the association between rs2231142 and gout. We searched "rs2231142 or Q141K and gout" in four databases and scholar searching website until 1 June, 2013 and included data from 52,010 participants in meta-analysis and subgroup analysis. The T allele of rs2231142 was associated with increased gout susceptibility (odds ratio [OR] [95 % confidence interval (95 % CI)] = 1.73 [1.55-1.91], P gout risk in Caucasians with OR (95 % CI) = 1.68 (1.50-1.87), P gout.

  8. Meta-Analysis of Transcriptome Data Related to Hippocampus Biopsies and iPSC-Derived Neuronal Cells from Alzheimer's Disease Patients Reveals an Association with FOXA1 and FOXA2 Gene Regulatory Networks.

    Science.gov (United States)

    Wruck, Wasco; Schröter, Friederike; Adjaye, James

    2016-01-01

    Although the incidence of Alzheimer's disease (AD) is continuously increasing in the aging population worldwide, effective therapies are not available. The interplay between causative genetic and environmental factors is partially understood. Meta-analyses have been performed on aspects such as polymorphisms, cytokines, and cognitive training. Here, we propose a meta-analysis approach based on hierarchical clustering analysis of a reliable training set of hippocampus biopsies, which is condensed to a gene expression signature. This gene expression signature was applied to various test sets of brain biopsies and iPSC-derived neuronal cell models to demonstrate its ability to distinguish AD samples from control. Thus, our identified AD-gene signature may form the basis for determination of biomarkers that are urgently needed to overcome current diagnostic shortfalls. Intriguingly, the well-described AD-related genes APP and APOE are not within the signature because their gene expression profiles show a lower correlation to the disease phenotype than genes from the signature. This is in line with the differing characteristics of the disease as early-/late-onset or with/without genetic predisposition. To investigate the gene signature's systemic role(s), signaling pathways, gene ontologies, and transcription factors were analyzed which revealed over-representation of response to stress, regulation of cellular metabolic processes, and reactive oxygen species. Additionally, our results clearly point to an important role of FOXA1 and FOXA2 gene regulatory networks in the etiology of AD. This finding is in corroboration with the recently reported major role of the dopaminergic system in the development of AD and its regulation by FOXA1 and FOXA2.

  9. Prognostic role of long non-coding RNA TUG1 expression in various cancers: a meta-analysis.

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    Zhou, Yongping; Lu, Yuxuan; Li, Runmin; Yan, Nana; Li, Xiding; Dai, Tu

    2017-11-21

    Several studies were conducted to explore the prognostic role of long non-coding RNA taurine upregulated gene 1 (lncRNA TUG1) expression in various cancers, with contradictory. This study aims to summarize the prognostic role of lncRNA TUG1 expression in various cancers. Embase, PubMed and Cochrane Library were completely retrieved. The cohort studies focusing on the prognostic role of lncRNA TUG1 expression in various cancers were eligible. The endpoints were overall survival (OS) and clinicopathological parameters. 9 studies involving a total of 1,078 patients were identified. The results showed that high lncRNA TUG1 expression was obviously associated with worse OS when compared to the low lncRNA TUG1 expression (HR = 1.37, 95% CI = 1.07-1.76, P = 0.01; I 2 = 85%). However, No distinct relationship was observed between the lncRNA TUG1 expression and age (OR = 0.99, 95% CI = 0.76-1.28, P = 0.92; I2 = 4%), gender (OR = 0.92, 95% CI = 0.70-1.22, P = 0.57; I 2 = 0%), diameter (OR = 0.83, 95% CI = 0.34-2.01, P = 0.67; I 2 = 85%), smoking (OR = 1.09, 95% CI = 0.37-3.21, P = 0.87; I 2 = 73%), TNM stage (OR = 0.60, 95% CI = 0.25-1.43, P = 0.25; I 2 = 86%) and lymph node metastasis (OR = 1.07, 95% CI = 0.47-2.45, P = 0.87; I 2 = 86%). In conclusion, it was revealed that high lncRNA TUG1 expression is an unfavorable predictor of OS in patients with cancers, and lncRNA TUG1 expression is a promising prognostic biomarker for various cancers.

  10. Association between insertion/deletion polymorphism in angiotensin-converting enzyme gene and acute lung injury/acute respiratory distress syndrome: a meta-analysis

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    Matsuda Akihisa

    2012-08-01

    Full Text Available Abstract Background A previous meta-analysis reported a positive association between an insertion/deletion (I/D polymorphism in the angiotensin-converting enzyme gene (ACE and the risk of acute lung injury (ALI/acute respiratory distress syndrome (ARDS. Here, we updated this meta-analysis and additionally assessed the association of this polymorphism with ALI/ARDS mortality. Methods We searched electronic databases through October 2011 for the terms “angiotensin-converting enzyme gene”, “acute lung injury”, and “acute respiratory distress syndrome,” and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in humans. Seven studies met the inclusion criteria, comprising 532 ALI/ARDS patients, 3032 healthy controls, and 1432 patients without ALI/ARDS. We used three genetic models: the allele, dominant, and recessive models. Results The ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS for any genetic model. However, the ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects ( Pallele Pdominant = 0.001, Precessive = 0.002. This finding remained significant after correction for multiple comparisons. Conclusions There is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians.

  11. Association of methylenetetrahydrofolate reductase gene C677T polymorphism with polycystic ovary syndrome risk: a systematic review and meta-analysis update.

    Science.gov (United States)

    Fu, Li-yuan; Dai, Li-meng; Li, Xiao-gang; Zhang, Kun; Bai, Yun

    2014-01-01

    To re-estimate the association between methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism and polycystic ovary syndrome (PCOS) risk by critically reviewing, analyzing and updating the current evidence. MTHFR C677T polymorphism has been studied as a possible risk factor for a variety of common conditions including heart disease, stroke and hypertension. Its association with PCOS was negative in a previous meta-analysis which had possible shortcomings. More studies have now been done but their results remain inconclusive. Available case-control studies containing genotype frequencies of MTHFR C677T were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. Statistical analyses were performed using software Review Manager (Version 5. 2) and Stata (Version 11.0). Nine case-control studies including 638 PCOS and 759 healthy controls were identified. Meta-analysis showed a significant effect in the dominant model (TT+CT vs. CC: OR=1.65, 95%CI=1.28-2.12, PPCOS risk in European populations (TT+CT vs. CC: OR=2.16, 95%CI=1.50-3.12, PPCOS susceptibility, and this relevance seems to be more intense in Europeans than in Asians. Copyright © 2013. Published by Elsevier Ireland Ltd.

  12. Prognostic significance of Cdx2 immunohistochemical expression in gastric cancer: a meta-analysis of published literatures

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    Wang Xiao-Tong

    2012-11-01

    Full Text Available Abstract Cdx2 is a homeobox domain-containing transcription factor that is important in the development and differentiation of the intestinal cells, and served as a potential biomarker of tumor progression in early intestinal-type gastric cancer. However, its prognostic value and significance in gastric cancer remain controversial. A meta-analysis based on published studies was performed to obtain an accurate evaluation of the association between the presence of Cdx2-positive in clinical samples and clinical outcome. A total of 13 eligible retrospective cohort studies with 1513 patients were included. Cdx2-positive cases were significantly associated with higher male-to-female ratio (RR=1.27, 95% CI: 1.17–1.38, PPP=0.002 fixed-effect and lymph node metastasis (RR=1.52, 95% CI: 1.33-1.73, PP

  13. 16S Ribosomal Ribonucleic Acid Gene Polymerase Chain Reaction in the Diagnosis of Bloodstream Infections: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Su, Guoming; Fu, Zhuqing; Hu, Liren; Wang, Yueying; Zhao, Zuguo; Yang, Weiqing

    2015-01-01

    We aim to evaluate the accuracy of the 16S ribosomal ribonucleic acid (rRNA) gene polymerase chain reaction (PCR) test in the diagnosis of bloodstream infections through a systematic review and meta-analysis. A computerized literature search was conducted to identify studies that assessed the diagnostic value of 16S rRNA gene PCR test for bloodstream infections. Study quality was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence intervals (95% CI) for each study. Summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. Statistical analysis was performed in Meta-DiSc 1.4 and Stata/SE 12.0 software. Twenty-eight studies were included in our meta-analysis. Using random-effect model analysis, the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.87 (95% CI, 0.85-0.89), 0.94 (95% CI, 0.93-0.95), 12.65 (95% CI, 8.04-19.90), 0.14 (95% CI, 0.08-0.24), and 116.76 (95% CI, 52.02-262.05), respectively. The SROC curve indicated that the area under the curve (AUC) was 0.9690 and the maximum joint sensitivity and specificity (Q*) was 0.9183. In addition, heterogeneity was statistically significant but was not caused by the threshold effect. Existing data suggest that 16S rRNA gene PCR test is a practical tool for the rapid screening of sepsis. Further prospective studies are needed to assess the diagnostic value of PCR amplification and DNA microarray hybridization of 16S rRNA gene in the future.

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

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    Yu-Jiao Wu

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

  15. A Comparative Genomic Study in Schizophrenic and in Bipolar Disorder Patients, Based on Microarray Expression Profiling Meta-Analysis

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    Marianthi Logotheti

    2013-01-01

    Full Text Available Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%–5% of the global population constitute two severe mental disorders. The catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. The aim of the study was to perform and interpret the results of a comparative genomic profiling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression profiling data. We performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the final study was performed based on raw data from a gene expression profiling dataset in the postmortem superior temporal cortex of schizophrenics. The data were downloaded from NCBI's GEO datasets.

  16. The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2 with aspirin insensitivity: a meta-analysis.

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    Zhiyuan Weng

    Full Text Available OBJECTIVE: Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643 from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2 with aspirin insensitivity via a meta-analysis. METHODS AND RESULTS: In total, there were 4 (353/595, 6 (344/698, 10 (588/878 and 7 (209/676 articles (patients/controls qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2. The risk estimate was expressed as odds ratio (OR and 95% confidence interval (95% CI. Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44-2.41; <0.0005 and rs1126643 (2.37; 1.44-3.89; 0.001 with aspirin insensitivity under allelic model. In subgroup analyses, the risk estimate for rs1126643 was greatly potentiated among patients with aspirin semi-resistance relative to those with aspirin resistance, especially under dominant model (aspirin semi-resistance: 5.44; 1.42-20.83; 0.013 versus aspirin resistance: 1.96; 1.07-3.6; 0.03. Further grouping articles by ethnicity observed a stronger prediction of all, but rs20417, examined polymorphisms for aspirin insensitivity in Chinese than in Caucasians. Finally, meta-regression analyses observed that the differences in percentage of coronary artery disease (P = 0.034 and averaged platelet numbers (P = 0.012 between two groups explained a large part of heterogeneity for rs20417 and rs1126643, respectively. CONCLUSION: Our findings provide strong evidence that COX-2 and ITGA2 genetic defects might increase the risk of having aspirin insensitivity, especially for aspirin semi-resistance and in Chinese populations.

  17. Estrogen receptor α gene polymorphisms and risk of Alzheimer’s disease: evidence from a meta-analysis

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    Cheng D

    2014-06-01

    Full Text Available Daye Cheng,1 Bin Liang,2 Yiwen Hao,1 Wenling Zhou1 1Department of Transfusion, First Hospital of China Medical University, Shenyang, 2Department of Clinical Laboratory, High Vocational Technological College, China Medical University, Shenyang, People’s Republic of China Objective: Human estrogen receptor α (ESR1, a member of the nuclear receptor superfamily of ligand-activated transcription factors, is one of the key mediators of hormonal response in estrogen-sensitive tissues. Accumulating evidence has demonstrated that two of the most widely studied single-nucleotide polymorphisms in ESR1 – PvuII (T/C, rs223493 and Xbal (A/G, rs9340799 – are possibly associated with Alzheimer’s disease (AD. However, individual study results are still controversial.Materials and methods: We searched PubMed, Embase, Web of Science, Science Direct, SpringerLink, and the Chinese National Knowledge Infrastructure databases for eligible studies assessing the association of ESR1 polymorphisms and AD risk (last search performed in November 2013. Thereafter, a meta-analysis of 13,192 subjects from 18 individual studies was conducted to evaluate the association between ESR1 polymorphisms and susceptibility to AD.Results: The results indicated that a significant association was found between the ESR1 PvuII polymorphism and AD risk in Caucasian populations (CC + CT versus TT, odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02–1.28, P=0.03; CT versus TT, OR 1.16, 95% CI 1.02–1.31, P=0.02, whereas no evidence of association was found in Asian populations. Nevertheless, we did not find any significant association between the ESR1 XbaI polymorphism and AD risk for any model in Caucasian and Asian populations (all P>0.05.Conclusion: Based on this meta-analysis, we conclude that the ESR1 PvuII polymorphism might be a risk factor in AD development in Caucasian populations, not in Asian populations. Further confirmation is needed from better-designed and

  18. Bayesian meta-analysis models for microarray data: a comparative study

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    Song Joon J

    2007-03-01

    Full Text Available Abstract Background With the growing abundance of microarray data, statistical methods are increasingly needed to integrate results across studies. Two common approaches for meta-analysis of microarrays include either combining gene expression measures across studies or combining summaries such as p-values, probabilities or ranks. Here, we compare two Bayesian meta-analysis models that are analogous to these methods. Results Two Bayesian meta-analysis models for microarray data have recently been introduced. The first model combines standardized gene expression measures across studies into an overall mean, accounting for inter-study variability, while the second combines probabilities of differential expression without combining expression values. Both models produce the gene-specific posterior probability of differential expression, which is the basis for inference. Since the standardized expression integration model includes inter-study variability, it may improve accuracy of results versus the probability integration model. However, due to the small number of studies typical in microarray meta-analyses, the variability between studies is challenging to estimate. The probability integration model eliminates the need to model variability between studies, and thus its implementation is more straightforward. We found in simulations of two and five studies that combining probabilities outperformed combining standardized gene expression measures for three comparison values: the percent of true discovered genes in meta-analysis versus individual studies; the percent of true genes omitted in meta-analysis versus separate studies, and the number of true discovered genes for fixed levels of Bayesian false discovery. We identified similar results when pooling two independent studies of Bacillus subtilis. We assumed that each study was produced from the same microarray platform with only two conditions: a treatment and control, and that the data sets

  19. Review Paper: Association of Transforming Growth Factor Beta-1 -509C/T Gene Polymorphism with Ischemic Stroke: A Meta Analysis

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    Pradeep Kumar

    2016-05-01

    Full Text Available Introduction: Transforming Growth Factor-Beta 1 (TGF-β1 is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS, by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS. Methods: A review of literature for eligible genetic association Studies published before October 20, 2014 was conducted in the PubMed, EMBASE, Google Scholar and Trip database. The strength of association was calculated by pooled odds ratios (ORs with 95% confidence intervals using RevMan 5.3 software. Heterogeneity was examined using Higgins I-squared, Tau-squared, and Chi-squared tests. Results: A total of 2 studies involving 614 cases and 617 controls were found. The overall estimates did not show any significant relation between TGF-β1-509C/T polymorphism and risk of IS under dominant (CC+CT vs. TT: OR=1.01, 95%CI=0.31 to 3.26; P=0.99, recessive (CC vs. CT+TT: OR=0.94, 95%CI=0.47 to 1.90; P=0.87, and allelic models (T vs. C: OR=1.06, 95%CI=0.55 to 2.04; P=0.86. Conclusion: This meta-analysis showed that TGF-β1-509C/T gene polymorphism has no significant association with the susceptibility of IS. Further well-designed prospective studies with larger sample size are needed to confirm these findings.

  20. The −675 4G/5G Polymorphism in Plasminogen Activator Inhibitor-1 Gene Is Associated with Risk of Asthma: A Meta-Analysis

    Science.gov (United States)

    Xiu, Qing-yu

    2012-01-01

    Background A number of studies assessed the association of −675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. Methods Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. Results Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12–2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06–1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17–2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07–1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08–1.68, P = 0.008). Conclusions This meta-analysis suggested that the −675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma. PMID:22479620

  1. The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: a meta-analysis.

    Science.gov (United States)

    Nie, Wei; Li, Bing; Xiu, Qing-Yu

    2012-01-01

    A number of studies assessed the association of -675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12-2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06-1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17-2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07-1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08-1.68, P = 0.008). This meta-analysis suggested that the -675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.

  2. The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Wei Nie

    Full Text Available BACKGROUND: A number of studies assessed the association of -675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. METHODS: Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI and Weipu Database were searched to find relevant studies. Odds ratios (ORs with 95% confidence intervals (CIs were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. RESULTS: Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12-2.18, P = 0.008, 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06-1.80, P = 0.02, 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17-2.76, P = 0.007, 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07-1.84, P = 0.02, and 4G vs. 5G (OR = 1.35, 95% CI 1.08-1.68, P = 0.008. CONCLUSIONS: This meta-analysis suggested that the -675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.

  3. Plasminogen activator inhibitor-1 4G/5G gene polymorphism and coronary artery disease in the Chinese Han population: a meta-analysis.

    Science.gov (United States)

    Li, Yan-yan

    2012-01-01

    The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI) was assessed by the random effect model. The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD.

  4. The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis

    DEFF Research Database (Denmark)

    Saetre, Peter; Lundmark, Per; Wang, August

    2010-01-01

    Serotonin (5-hydroxytryptamin; 5-HT) alternations has since long been suspected in the pathophysiology of schizophrenia. Tryptophan hydroxylase (tryptophan 5-monooxygenase; TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT, and sequence variation in intron 6 of the TPH1 gene has been...... affected individuals having attempted suicide at least once and patients with no history of suicide attempts (P = 0.84). A systematic literature review and meta-analysis support the A218C polymorphism as a susceptibility locus for schizophrenia (odds ratio 1.17, 95% confidence interval 1.......07-1.29). Association studies on suicide attempts are however conflicting (heterogeneity index I(2) = 0.54) and do not support the A218C/A779C polymorphisms being a susceptibility locus for suicidal behavior among individuals diagnosed with a psychiatric disorder (OR = 0.96 [0.80-1.16]). We conclude that the TPH1 A218...

  5. Meta-Analysis of Public Microarray Datasets Reveals Voltage-Gated Calcium Gene Signatures in Clinical Cancer Patients.

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    Chih-Yang Wang

    Full Text Available Voltage-gated calcium channels (VGCCs are well documented to play roles in cell proliferation, migration, and apoptosis; however, whether VGCCs regulate the onset and progression of cancer is still under investigation. The VGCC family consists of five members, which are L-type, N-type, T-type, R-type and P/Q type. To date, no holistic approach has been used to screen VGCC family genes in different types of cancer. We analyzed the transcript expression of VGCCs in clinical cancer tissue samples by accessing ONCOMINE (www.oncomine.org, a web-based microarray database, to perform a systematic analysis. Every member of the VGCCs was examined across 21 different types of cancer by comparing mRNA expression in cancer to that in normal tissue. A previous study showed that altered expression of mRNA in cancer tissue may play an oncogenic role and promote tumor development; therefore, in the present findings, we focus only on the overexpression of VGCCs in different types of cancer. This bioinformatics analysis revealed that different subtypes of VGCCs (CACNA1C, CACNA1D, CACNA1B, CACNA1G, and CACNA1I are implicated in the development and progression of diverse types of cancer and show dramatic up-regulation in breast cancer. CACNA1F only showed high expression in testis cancer, whereas CACNA1A, CACNA1C, and CACNA1D were highly expressed in most types of cancer. The current analysis revealed that specific VGCCs likely play essential roles in specific types of cancer. Collectively, we identified several VGCC targets and classified them according to different cancer subtypes for prospective studies on the underlying carcinogenic mechanisms. The present findings suggest that VGCCs are possible targets for prospective investigation in cancer treatment.

  6. Gene expression and gene therapy imaging

    International Nuclear Information System (INIS)

    Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

    2007-01-01

    The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

  7. Association between Two Common Missense Substitutions, Thr6Lys and Val81Ile, in MC3R Gene and Childhood Obesity: A Meta-Analysis.

    Science.gov (United States)

    Koya, Charita; Yu, Tsung; Strong, Carol; Tsai, Meng-Che

    2018-04-24

    Two common missense variants in the melanocortin-3 receptor (MC3R) gene, Thr6Lys (T6K) and Val81Ile (V81I), are presumably correlated with pediatric obesity. This meta-analysis aimed to examine and synthesize evidence on the association between these two common MC3R polymorphisms and the development of childhood obesity. A combination of words relevant to the research question was searched on PubMed, EMBASE, Scopus, and the Cochrane database. Results were restricted to human studies, specifically child and adolescent populations. Articles were excluded based on accessibility of full online texts and availability of pertinent data. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model to determine the association of the polymorphisms with obesity. Searches on the databases using the keywords identified 65 potentially relevant reports. Among them, 32 studies were excluded due to irrelevance, and 28 studies excluded due to lack of access, insufficient data, and investigation of other variants. A final set of five studies included in this meta-analysis found that the risk of overweight/obesity increased by 46.1% per K allele and 21.7% per I allele. Only homozygous genotypes for T6K were associated with a 3.10-fold (95% CI: 1.29-7.43) increased risk of overweight/obesity in children. Data were insufficient to examine if homozygosity for both rare alleles further increases risk. Our results supported a recessive inheritance model for MC3R gene as a potential cause of childhood obesity. High clinical heterogeneity existed among studies and thus requires more research of larger participation for future integration of data.

  8. The roles of variants in human multidrug resistance (MDR1 gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies.

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    Hui Li

    Full Text Available Previous studies reported the associations between the ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1 polymorphisms and their haplotypes with risk of response to antiepileptic drugs in epilepsy, however, the results were inconclusive.The Pubmed, Embase, Web of Science, CNKI and Chinese Biomedicine databases were searched up to July 15, 2014. Pooled odds ratios (ORs and 95% confidence intervals (CIs were calculated using a fixed-effects or random-effects model based on heterogeneity tests. Meta-regression and Galbraith plot analysis were carried out to explore the possible heterogeneity.A total of 57 studies involving 12407 patients (6083 drug-resistant and 6324 drug-responsive patients with epilepsy were included in the pooled-analysis. For all three polymorphisms (C3435T, G2677T/A, and C1236T, we observed a wide spectrum of minor allele frequencies across different ethnicities. A significantly decreased risk of AEDs resistance was observed in Caucasian patients with T allele of C3435T variant, which was still significant after adjusted by multiple testing corrections (T vs C: OR=0.83, 95%CI=0.71-0.96, p=0.01. However, no significant association was observed between the other two variants and AEDs resistance. Of their haplotypes in ABCB1 gene (all studies were in Indians and Asians, no significant association was observed with AEDs resistance. Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable.In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians. Additionally, further studies in different ethnic groups are warranted to clarify possible roles of haplotypes in ABCB1 gene in AEDs resistance, especially in Caucasians.

  9. Meta-analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

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    Wen-Ying Fan

    2015-06-01

    Full Text Available AIM:To collectively evaluate the association of intercellular adhesion molecule-1 (ICAM-1 gene K469E polymorphism (rs5498 with diabetic retinopathy (DR in patients with type 2 diabetic mellitus (T2DM.METHODS:Overall review of available literatures relating K469E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios (ORs. Potential sources of heterogeneity and bias were explored.RESULTS:Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469E polymorphism with DR (P>0.05. A statistically significant association was detected between the K469E polymorphism and proliferative diabetic retinopathy (PDR in Asians only in dominant model (GG+AG vs AA with pooled OR of 0.729 (95%CI:0.564-0.942, P=0.016, Pheterogeneity=0.143, however, this association was not detected in recessive model (GA+AA vs GG; OR=1.178, 95%CI:0.898-1.545, P=0.236, Pheterogeneity=0.248 or allelic model (G vs A; OR=0.769, 95% CI:0.576-1.026, P=0.074, Pheterogeneity=0.094. No publication bias was found by Funnel plot, Begg''s and Egger''s test.CONCLUSION:This research found no statistically significant association between ICAM-1 gene K469E polymorphism and DR in patients with T2DM, but showed significant association of the K469E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion.

  10. The association of HMGB1 expression with clinicopathological significance and prognosis in Asian patients with colorectal carcinoma: a meta-analysis and literature review

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    Zhang XL

    2016-08-01

    Full Text Available Xiaoli Zhang,1,2 Jinming Yu,1,2 Minghuan Li,2 Hui Zhu,2 Xindong Sun,2 Li Kong2 1Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong Province, People’s Republic of China Background: The association of high mobility group box 1 (HMGB1 expression with clinicopathological significance and prognosis in Asian patients with colorectal carcinoma (CRC remains controversial. The purpose of this study was to conduct a meta-analysis and literature review to identify the role of HMGB1 in the development and prognosis of CRC in Asians. Methods: All eligible studies regarding the association between HMGB1 expression in tissue with clinicopathological significance and prognosis in Asian patients with CRC published up to January 2015 were identified by searching PubMed, Web of Science, Chinese National Knowledge Infrastructure, and WanFang database. Analysis of pooled data was performed, while odds ratio (OR or hazard radio with 95% confidence interval (CI was calculated and summarized to evaluate the strength of this association in fixed- or random-effects model. Results: The expression level of HMGB1 in CRC tissues was much higher than normal colorectal tissues (OR =27.35, 95% CI 9.32–80.26, P<0.0001 and para-tumor colorectal tissues (OR =10.06, 95% CI 4.61–21.95, P<0.0001. There was no relation between the HMGB1 expression and sex, age, clinical T stage, tumor size, and location (colon or rectum cancer. However, a significant relation was detected between the HMGB1 expression and clinical stage (American Joint Committee on Cancer 7, lymph node metastasis, distant metastasis, tumor invasion depth, and differentiation rate (P=0.002, P≤0.0001, P<0.0001, P<0.0001, and P=0.007, respectively. Patients with higher HMGB1 expression had shorter overall survival time, whereas patients with lower level of HMGB1 had better survival (hazard

  11. Effect of Expressive Writing Intervention on Health Outcomes in Breast Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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    Chunlan Zhou

    Full Text Available Numerous randomized controlled trials (RCTs have arrived at conflicting conclusions on expressive writing (EW as an intervention for breast cancer (BC patients, but there has been no meta-analysis of these studies to assess the effectiveness of EW in BC population.PubMed, Web of Science, The Cochrane Library, EMBASE, and CINAHL and the www.clinicaltrial.gov database on ongoing clinical trials were searched to identify all the RCTs investigating efficacy of EW on the physical and psychological health in BC patients. The risk of bias of the original studies was assessed using the Cochrane Collaboration's tool. Our primary outcomes for physical and psychological health were respectively negative somatic symptoms and negative mood which were stratified by emotional, benefit-finding and multiple prompts in sub-group analyses. The data were analyzed using Review Manager 5.2 and Stata version 12.0 statistical software.Of the 5,232 titles screened, we identified 11 RCTs with a total of 1,178 participants. The pooled results showed a significant effect of EW using either an emotional prompt or a benefit-finding prompt on reducing negative somatic symptoms in BC patients in the ≤3-month follow-up group [Mean Difference (MD, -13.03, 95% CI, -19.23 to -6.83, P3-month follow-up group. There were no significant differences regarding psychological health indexes between EW intervention and control groups at any of the follow-up time-points (P>0.05.This systematic review and meta-analysis reveals that EW intervention may have a significantly positive impact on the physical health but not the psychological health in BC patients, but this benefit may not last long. However, further high-quality studies with more homogeneity are needed to confirm the current findings.

  12. The association between gene polymorphism of TCF7L2 and type 2 diabetes in Chinese Han population: a meta-analysis.

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    Haoying Dou

    Full Text Available In recent years, it has been widely accepted that transcription factor 7-like 2 (TCF7L2 is associated with type 2 diabetes mellitus (T2DM in multiple ethnic groups, especially its single nucleotide polymorphisms of rs7903146C/T, rs12255372G/T and rs290487T/C. However, the results previously obtained in Chinese Han population are often inconsistent. For clearing this issue, herein we performed meta-analysis based on the reports that can be found to assess the association. In the meta-analysis, Odds ratio (OR and 95% confidence interval (95% CI were calculated with random-effect model or fixed-effect model based on the heterogeneity analysis. The quality of included studies was evaluated by using the Newcastle-Ottawa Scale. The sensitivity analysis was used to confirm the reliability and stability of the meta-analysis. In total, 20 case-control studies with 9122 cases of T2DM and 8017 controls were included. Among these case-control studies, we selected 13 ones on rs7903146 C/T, 5 ones on rs12255372 G/T, 8 ones on rs290487 T/C. The results indicated that rs7903146C/T polymorphism was significantly associated with T2DM (T vs. C, OR = 1.73, 95% CI = 1.39-2.16. There was no evidence that rs12255372G/T and rs290487T/C polymorphisms increased T2DM risk (T vs. G, OR = 1.77, 95% CI = 0.88-3.56; C vs. T, OR = 1.08, 95% CI = 0.93-1.25. Subgroup analysis of different regions proved the relationship between rs7903146C/T polymorphism and T2DM risk in both the northern and the southern China. The association of rs290487 with T2DM was affected by body mass index, whereas the association of rs7903146 and rs290487 with T2DM was influenced neither by age nor by sex. In conclusion, this study indicated that the rs7903146C/T polymorphism of the TCF7L2 gene had a significant effect on T2DM risk in Chinese Han population, with rs12255372G/T and rs290487T/C polymorphisms showing no significant effect.

  13. Cross-study analysis of gene expression data for intermediate neuroblastoma identifies two biological subtypes

    International Nuclear Information System (INIS)

    Warnat, Patrick; Oberthuer, André; Fischer, Matthias; Westermann, Frank; Eils, Roland; Brors, Benedikt

    2007-01-01

    Neuroblastoma patients show heterogeneous clinical courses ranging from life-threatening progression to spontaneous regression. Recently, gene expression profiles of neuroblastoma tumours were associated with clinically different phenotypes. However, such data is still rare for important patient subgroups, such as patients with MYCN non-amplified advanced stage disease. Prediction of the individual course of disease and optimal therapy selection in this cohort is challenging. Additional research effort is needed to describe the patterns of gene expression in this cohort and to identify reliable prognostic markers for this subset of patients. We combined gene expression data from two studies in a meta-analysis in order to investigate differences in gene expression of advanced stage (3 or 4) tumours without MYCN amplification that show contrasting outcomes (alive or dead) at five years after initial diagnosis. In addition, a predictive model for outcome was generated. Gene expression profiles from 66 patients were included from two studies using different microarray platforms. In the combined data set, 72 genes were identified as differentially expressed by meta-analysis at a false discovery rate (FDR) of 8.33%. Meta-analysis detected 34 differentially expressed genes that were not found as significant in either single study. Outcome prediction based on data of both studies resulted in a predictive accuracy of 77%. Moreover, the genes that were differentially expressed in subgroups of advanced stage patients without MYCN amplification accurately separated MYCN amplified tumours from low stage tumours without MYCN amplification. Our findings support the hypothesis that neuroblastoma consists of two biologically distinct subgroups that differ by characteristic gene expression patterns, which are associated with divergent clinical outcome

  14. Down-regulated E-cadherin expression is associated with poor five-year overall survival in bone and soft tissue sarcoma: results of a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Ning Wang

    Full Text Available To conduct a meta-analysis to evaluate the prognostic role of E-cadherin expression in bone and soft tissue sarcomas.The PubMed, EMBASE, and Web of Science databases were searched using terms related to E-cadherin, sarcoma, and prognosis for all articles published in English before March 2014. Pooled effect was calculated from the available data to evaluate the association between negative E-cadherin expression and 5-year overall survival and tumor clinicopathological features in sarcoma patients. Pooled odds ratios (OR and risk ratios (RR with 95% confidence intervals (CI were calculated using a fixed-effects model.Eight studies met the selection criteria and reported on 812 subjects. A total of 496 subjects showed positive E-cadherin expression (59.9%. Negative E-cadherin expression in bone and soft tissue sarcomas was correlated with lower 5-year overall survival (OR = 3.831; 95% CI: 2.246-6.534, and was associated with higher clinical stage (RR = 1.446; 95% CI: 1.030-2.028 and with male sex (RR = 0.678; 95% CI: 0.493-0.933.In the E-cadherin negative group, 5-year overall survival was significantly worse than in the E-cadherin positive group. However, further studies are required to confirm these results.

  15. Prognostic value and clinicopathological significance of serum- and tissue-based cytokeratin 18 express level in breast cancer: a meta-analysis.

    Science.gov (United States)

    Yang, Jiangling; Gao, Sicheng; Xu, Jian; Zhu, Junfeng

    2018-04-27

    Cytokeratin 18 (CK18), a type I cytokeratin of the intermediate filament family, has been associated with the prognosis of cancer patients for decades. However, its exact role in predicting the clinical outcome of breast cancer remains controversial. To comprehensively investigated the prognostic value of CK18 in breast cancer, a systematically meta-analysis was conducted to explore the association between CK18 expression and overall survival. Literature collection was conducted by retrieving electronic databases Pubmed, Cochrane Library, Web of Science, EMBASE, and OVID completely (up to January 1, 2017). Nine relevant studies with 4857 cases assessing the relationship between CK18 high expression and the outcome of breast cancer patients were enrolled in our analysis. The results indicated that the high level of CK18 expression was significantly associated with overall survival of breast cancer patients via a specimen-depended manner. Reports which used serum to detect the expression of CK18 predicted a poor outcome of breast cancer (HR = 1.24, 95%CI: 1.11-1.38, P present study demonstrated that CK18 might be served as a novel biomarker to predict clinicopathological features and the outcome of breast cancer. © 2018 The Author(s).

  16. Implicating the H63D polymorphism in the HFE gene in increased incidence of solid cancers: a meta-analysis.

    Science.gov (United States)

    Shen, L L; Gu, D Y; Zhao, T T; Tang, C J; Xu, Y; Chen, J F

    2015-10-29

    A number of previous studies have demonstrated that the HFE H63D polymorphism is associated with increased risk of incidence multiple types of cancer, including colorectal cancer, breast cancer, liver cancer, pancreatic cancer, and gynecological malignant tumors. However, the clinical outcomes were inconsistent. Therefore, this meta-analysis was conducted to summarize the effect of the H63D variant on the incidence of solid tumor. PubMed and EMBASE databases were searched for articles associating the HFE H63D polymorphism with cancer risk. The relationships were evaluated by calculating the pooled odds ratios (ORs) with 95% confidence intervals (CIs). A total of 28 studies, including 7728 cancer cases and 11,895 controls, were identified. Statistically significant associations were identified between the HFE H63D polymorphism and solid cancer risk (CG vs CC, OR = 1.14, 95%CI = 1.07-1.23, P HFE H63D polymorphism may play a critical role in the increased aggressiveness of hepatocellular carcinoma and pancreatic cancer.

  17. The association between the C282Y and H63D polymorphisms of HFE gene and the risk of Parkinson's disease: A meta-analysis.

    Science.gov (United States)

    Xia, Jianjian; Xu, Huamin; Jiang, Hong; Xie, Junxia

    2015-05-19

    Impaired brain iron homeostasis has been considered as an important mechanism in Parkinson's diseases (PD). There are indications that C282Y and H63D polymorphisms of HFE genes involved in iron metabolism might contribute to the pathogenesis of PD in some cases. However, the investigation of the relationship between PD and the two polymorphisms had produced contradictory results. We performed a meta-analysis to assess the C282Y and H63D polymorphisms of HFE in PD susceptibility. PubMed, EMBASE and Web of Science were systematically searched to identify relevant researches. The strict selection criteria and exclusion standard were applied. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A fixed-effect or random-effect model was selected, depending on the results of the heterogeneity test. Fifteen studies were included in the meta-analysis (eight studies with 1631 cases and 4548 controls for C282Y; seven studies with 1192 cases and 4065 controls for H63D). For the C282Y polymorphism, significant associations were observed in the Recessive model (YY vs CY+CC: OR=0.22, 95% CI=0.09-0.57, P=0.002). This indicated that the C282Y polymorphism in HFE might be a potential protective factor for PD. However, no significant associations were found for any genetic model for the H63D polymorphism, suggesting that the H63D polymorphism might not be associated with PD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Association between C282Y and H63D mutations of the HFE gene with hepatocellular carcinoma in European populations: a meta-analysis

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    Shen Xi-Zhong

    2010-03-01

    Full Text Available Abstract Background Hereditary hemochromatosis (HH is an autosomal recessive disorder mainly associated with homozygosity for the C282Y and H63D mutations in the hemochromatosis (HFE gene. The reports about the C282Y and H63D mutations and hepatocellular carninoma (HCC were controversial. To clarify the relationship between C282Y and H63D mutations and HCC, a meta-analysis including nine studies (1102 HCC cases and 3766 controls, mainly came from European populations was performed. Methods The association was measured using random-effect (RE or fixed-effect (FE odds ratios (ORs combined with 95% confidence intervals (CIs according to the studies' heterogeneity. Results Meta-analysis of nine studies showed that Y allele of C282Y was associated with HCC risk: RE OR reached 1.50 (95%CI: 1.05-2.14, p for heterogeneity = 0.02, I2 = 0.57. Subgroup analysis of seven studies also showed Y allele was associated with HCC risk in healthy populations: RE OR reached 1.61 (95%CI: 1.08-2.39, p for heterogeneity = 0.04, I2 = 0.55. We further did subgroup analysis in alcoholic liver cirrhosis (LC patients of four studies (224 cases and 380 controls and found that both the dominant model and Y allele of C282Y were associated with HCC risk (FE OR reached 4.06, 95%CI: 2.08-7.92 and 3.41, 95%CI: 1.81-6.41, respectively. There was no distinct heterogeneity among the studies (I2 = 0. Sensitivity analyses showed the results were robust in the subgroup analysis of alcoholic LC patients. Conclusions C282Y mutation was associated with HCC in European alcoholic LC patients.

  19. IL1 receptor antagonist gene IL1-RN variable number of tandem repeats polymorphism and cancer risk: a literature review and meta-analysis.

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    Ying Zhang

    Full Text Available IL1 receptor antagonist (IL1RA and IL1beta (IL1β, members of the pro-inflammatory cytokine interleukin-1 (IL1 family, play a potential role against infection and in the pathogenesis of cancers. The variable number of tandem repeats (VNTR polymorphism in the second intron of the IL1 receptor antagonist gene (IL1-RN and a polymorphism in exon 5 of IL1B (IL1B+3954C>T, rs1143634 have been suggested in predisposition to cancer risk. However, studies have shown inconsistent results. To validate any association, a meta-analysis was performed with 14,854 cases and 19,337 controls from 71 published case-control studies for IL1-RN VNTR and 33 eligible studies contained 7,847 cases and 8917 controls for IL1B +3954. Odds ratios (ORs with 95% confidence intervals (CIs were calculated from comparisons to assess the strength of the association. There was significant association between the IL1-RN VNTR polymorphism and the risk of cancer for any overall comparison. Furthermore, cancer type stratification analysis revealed that there were significantly increased risks of gastric cancer, bladder cancer and other cancer groups. Infection status analysis indicated that the H. pylori or HBV/HCV infection and IL1-RN VNTR genotypes were independent factors for developing gastric or hepatocellular cancers. In addition, a borderline significant association was observed between IL1B+3954 polymorphism and the increased cancer risk. Although some modest bias could not be eliminated, this meta-analysis suggested that the IL1-RN VNTR polymorphisms may contribute to genetic susceptibility to gastric cancer. More studies are needed to further evaluate the role of the IL1B+3954 polymorphism in the etiology of cancer.

  20. Meta-analysis with R

    CERN Document Server

    Schwarzer, Guido; Rücker, Gerta

    2015-01-01

    This book provides a comprehensive introduction to performing meta-analysis using the statistical software R. It is intended for quantitative researchers and students in the medical and social sciences who wish to learn how to perform meta-analysis with R. As such, the book introduces the key concepts and models used in meta-analysis. It also includes chapters on the following advanced topics: publication bias and small study effects; missing data; multivariate meta-analysis, network meta-analysis; and meta-analysis of diagnostic studies.  .

  1. Polymorphisms of three genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system are not associated with blood pressure salt sensitivity: A systematic meta-analysis.

    Science.gov (United States)

    Sun, Jiahong; Zhao, Min; Miao, Song; Xi, Bo

    2016-01-01

    Many studies have suggested that polymorphisms of three key genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system (RAAS) play important roles in the development of blood pressure (BP) salt sensitivity, but they have revealed inconsistent results. Thus, we performed a meta-analysis to clarify the association. PubMed and Embase databases were searched for eligible published articles. Fixed- or random-effect models were used to pool odds ratios and 95% confidence intervals based on whether there was significant heterogeneity between studies. In total, seven studies [237 salt-sensitive (SS) cases and 251 salt-resistant (SR) controls] for ACE gene I/D polymorphism, three studies (130 SS cases and 221 SR controls) for AGT gene M235T polymorphism and three studies (113 SS cases and 218 SR controls) for CYP11B2 gene C344T polymorphism were included in this meta-analysis. The results showed that there was no significant association between polymorphisms of these three polymorphisms in the RAAS and BP salt sensitivity under three genetic models (all p > 0.05). The meta-analysis suggested that three polymorphisms (ACE gene I/D, AGT gene M235T, CYP11B2 gene C344T) in the RAAS have no significant effect on BP salt sensitivity.

  2. A meta-analysis of the effects of the 5-hydroxytryptamine transporter gene-linked promoter region polymorphism on susceptibility to lifelong premature ejaculation.

    Directory of Open Access Journals (Sweden)

    Lijie Zhu

    Full Text Available OBJECTIVE: Premature ejaculation (PE has been reported as the most common male sexual dysfunction with global prevalence rates estimated at approximately 30%. The neurobiogenesis of ejaculation is very complex and involves the serotoninergic (5-hydroxytryptamine, 5-HT system. Recently, genetic polymorphisms located on SLC6A4 gene codifying for 5-HT transporter (5-HTT, the major regulator of serotonic neurotransmission, have been linked with the pathogenesis and risk of PE. Apparently studies of this type of polymorphism in PE have show conflicting results. METHODS: A meta-analysis was performed that are available in relation with 5-HTT gene-linked promoter region (5-HTTLPR polymorphism and the risk of lifelong PE (LPE in men to clarify this relationship. We searched Pubmed and Embase (last search updated on Aug 2012 using 'premature ejaculation', 'polymorphism or variant', 'genotype', 'ejaculatory function', and 'rapid ejaculation' as keywords and reference lists of studies corresponded to the inclusion criteria for meta-analysis. These studies involved the total number of 481 LPE men and 466 health control men subjects. Odds ratio (OR and 95% confidence intervals (CIs were used to evaluate this relationship. RESULTS: In the overall analysis, significant associations between LPE risk and 5-HTTLPR polymorphism were found (L-allele vs. S-allele OR = 0.86, 95% CI = 0.79-0.95, P = 0.002; LL vs. SS: OR = 0.80, 95% CI = 0.68-0.95, P = 0.009; LS vs. SS: OR = 0.85, 95% CI = 0.76-0.97, P = 0.012 and LL+LS vs. SS: OR = 0.88, 95% CI = 0.81-0.95, P = 0.002. Moreover, in subgroup analysis based on ethnicity, similar significant associations were detected. The Egger's test did not reveal presence of a publication bias. CONCLUSIONS: Our investigations demonstrate that 5-HTTLPR (L>S polymorphism might protect men against LPE risk. Further studies based on larger sample size and gene-environment interactions should

  3. Is Ep-CAM Expression a Diagnostic and Prognostic Biomarker for Colorectal Cancer? A Systematic Meta-Analysis

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    Susu Han

    2017-06-01

    Conclusions: The present findings suggest that Ep-CAM expression may be associated with CRC carcinogenesis, while the loss of Ep-CAM expression is correlated with the progression, metastasis, and poor prognosis of CRC. Ep-CAM expression may be a useful biomarker for the clinical diagnosis of CRC.

  4. a meta-analysis

    Indian Academy of Sciences (India)

    Chrissa G. Tsiara

    2018-03-13

    Mar 13, 2018 ... a meta-analysis of case–control studies was conducted. Univariate and ...... recent hepatitis C virus: potential benefit for ribavirin use in. HCV/HIV ... C/G polymorphism in breast pathologies and in HIV-infected patients.

  5. 4G/5G polymorphism of plasminogen activator inhibitor-1 gene is associated with polycystic ovary syndrome in Chinese patients: a meta-analysis.

    Science.gov (United States)

    Wang, Li-Hong; Wang, Li-Mei; Zhou, Na

    2015-09-01

    To date, case-control studies on the association between a single-nucleotide polymorphism (SNP) in the plasminogen activator inhibitor-1 (PAI-1) gene and polycystic ovary syndrome (PCOS) have provided controversial results. The electronic databases PubMed, Embase, Web of Science, and CNKI (China National Knowledge Infrastructure) were searched for studies to include in the present meta-analysis. The fixed effects and random effects models showed that the 4G allele was associated with a risk of PCOS compared with the 5G allele in Chinese patients (OR = 2.05; 95 % CI = 1.56-2.69), but not in Caucasian patients (OR = 1.05; 95 % CI = 0.81-1.37). The contrast of homozygotes and the recessive and dominant models produced the same pattern of results as the allele contrast. Our pooled data suggest evidence for a major role of PAI-1 gene 4G/5G polymorphism in the pathogenesis of PCOS among Chinese patients.

  6. Acupoint stimulation, massage therapy and expressive writing for breast cancer: A systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Lee, Phoebe Lyssandra Tan; Tam, Ka-Wai; Yeh, Mei-Ling; Wu, Wei-Wen

    2016-08-01

    Researches have accumulated using non-pharmacologic interventions including acupoint stimulation, massage therapy and expressive writing to manage breast cancer-related symptoms. Results from randomized controlled trials (RCTs) can get contradictory. A systematic review and meta-analysis were conducted to determine the effects on the quality of life, negative emotions and disease-related symptoms among women with breast cancer. Two independent researchers performed a structured search using data sources including MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, PubMed and PsychINFO from the beginning of time until the first week of January 2015. A total of 23 acupoint stimulation, massage therapy and expressive writing RCTs were included in the review. The study showed that no single intervention could be put under the spotlight exhibiting an overall effective result on all measured outcomes; however, looking into each one in detail shows different results in specific outcomes. Among the three interventions, acupoint stimulation has a treatment effect for general pain (MD=-1.46, 95% CI=-2.38 to -0.53) and fatigue (MD=-2.22, 95% CI=-3.68 to -0.77), massage therapy has a treatment effect for anxiety (MD=-0.50, 95% CI=-0.77 to -0.24), and expressive writing has a treatment effect for quality of life (MD=7.18, 95% CI=0.38 to 13.98). The measurement other outcomes showed either ineffective or equivocal results. Non-pharmacologic interventions including acupoint stimulation, massage therapy and expressive writing have an effect on a middle-age woman with breast cancer. However, because of limitations, the seemingly promising results should be interpreted with caution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Microarray Meta-Analysis Identifies Acute Lung Injury Biomarkers in Donor Lungs That Predict Development of Primary Graft Failure in Recipients

    Science.gov (United States)

    Haitsma, Jack J.; Furmli, Suleiman; Masoom, Hussain; Liu, Mingyao; Imai, Yumiko; Slutsky, Arthur S.; Beyene, Joseph; Greenwood, Celia M. T.; dos Santos, Claudia

    2012-01-01

    Objectives To perform a meta-analysis of gene expression microarray data from animal studies of lung injury, and to identify an injury-specific gene expression signature capable of predicting the development of lung injury in humans. Methods We performed a microarray meta-analysis using 77 microarray chips across six platforms, two species and different animal lung injury models exposed to lung injury with or/and without mechanical ventilation. Individual gene chips were classified and grouped based on the strategy used to induce lung injury. Effect size (change in gene expression) was calculated between non-injurious and injurious conditions comparing two main strategies to pool chips: (1) one-hit and (2) two-hit lung injury models. A random effects model was used to integrate individual effect sizes calculated from each experiment. Classification models were built using the gene expression signatures generated by the meta-analysis to predict the development of lung injury in human lung transplant recipients. Results Two injury-specific lists of differentially expressed genes generated from our meta-analysis of lung injury models were validated using external data sets and prospective data from animal models of ventilator-induced lung injury (VILI). Pathway analysis of gene sets revealed that both new and previously implicated VILI-related pathways are enriched with differentially regulated genes. Classification model based on gene expression signatures identified in animal models of lung injury predicted development of primary graft failure (PGF) in lung transplant recipients with larger than 80% accuracy based upon injury profiles from transplant donors. We also found that better classifier performance can be achieved by using meta-analysis to identify differentially-expressed genes than using single study-based differential analysis. Conclusion Taken together, our data suggests that microarray analysis of gene expression data allows for the detection of

  8. Imaging gene expression in gene therapy

    International Nuclear Information System (INIS)

    Wiebe, Leonard I.

    1997-01-01

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented

  9. Imaging gene expression in gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

    1997-12-31

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

  10. Transcriptomic Analysis and Meta-Analysis of Human Granulosa and Cumulus Cells.

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    Tanja Burnik Papler

    Full Text Available Specific gene expression in oocytes and its surrounding cumulus (CC and granulosa (GC cells is needed for successful folliculogenesis and oocyte maturation. The aim of the present study was to compare genome-wide gene expression and biological functions of human GC and CC. Individual GC and CC were derived from 37 women undergoing IVF procedures. Gene expression analysis was performed using microarrays, followed by a meta-analysis. Results were validated using quantitative real-time PCR. There were 6029 differentially expressed genes (q < 10-4; of which 650 genes had a log2 FC ≥ 2. After the meta-analysis there were 3156 genes differentially expressed. Among these there were genes that have previously not been reported in human somatic follicular cells, like prokineticin 2 (PROK2, higher expressed in GC, and pregnancy up-regulated nonubiquitous CaM kinase (PNCK, higher expressed in CC. Pathways like inflammatory response and angiogenesis were enriched in GC, whereas in CC, cell differentiation and multicellular organismal development were among enriched pathways. In conclusion, transcriptomes of GC and CC as well as biological functions, are distinctive for each cell subpopulation. By describing novel genes like PROK2 and PNCK, expressed in GC and CC, we upgraded the existing data on human follicular biology.

  11. The clinical pathological characteristics and prognosis of FGFR1 gene amplification in non-small-cell lung cancer: a meta-analysis

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    Xie FJ

    2016-01-01

    Full Text Available Fa-Jun Xie,1,2 Hong-Yang Lu,1,3 Qiu-Qing Zheng,3 Jing Qin,1,3 Yun Gao,3 Yi-Ping Zhang,1,3 Xun Hu,2 Wei-Min Mao3,4 1Department of Medical Oncology, Zhejiang Cancer Hospital, 2Cancer Institute (Key Laboratory for Cancer Intervention and Prevention, China National Ministry of Education, Zhejiang Provincial Key Laboratory of Molecular Biology in Medical Sciences, Second Affiliated Hospital, Zhejiang University School of Medicine,3Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus, Hangzhou, 4Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China Abstract: FGFR1 amplification is recognized as a novel therapy target for non-small-cell lung cancer (NSCLC, especially in squamous cell carcinoma (SCC. However, the association between FGFR1 amplification and the clinicopathological characteristics of NSCLC remains controversial. We performed a meta-analysis of 17 eligible studies to examine the correlation between FGFR1 gene amplification and clinicopathological characteristics. FGFR1 amplification was closely related to these clinicopathological features, including sex (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.50–2.80, smoking (OR 3.31, 95% CI 2.02–5.44, and histology (OR 3.60, 95% CI 2.82–4.59. FGFR1 amplification was associated with shorter overall survival, and no significant heterogeneity existed between studies (I2=3.8%. We should note that publication bias may partly account for these results, but our findings remained significant after the trim-and-fill method (hazard ratio 1.22, 95% CI 1.06–1.40. However, no significant correlation was found with poor disease-free survival (hazard ratio 1.43, 95% CI 0.96–2.12. In conclusion, this study showed that FGFR1 amplification was significantly associated with sex, smoking, and histology. FGFR1 amplification could be a marker of poor prognosis in NSCLC patients, especially in SCC patients

  12. Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

    Science.gov (United States)

    Lasram, Khaled; Ben Halim, Nizar; Hsouna, Sana; Kefi, Rym; Arfa, Imen; Ghazouani, Welid; Jamoussi, Henda; Benrahma, Houda; Kharrat, Najla; Rebai, Ahmed; Ben Ammar, Slim; Bahri, Sonia; Barakat, Abdelhamid; Abid, Abdelmajid; Abdelhak, Sonia

    2014-01-01

    Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.). Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, and P = 0.007). Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, and P < 10−3 and OR = 1.33, 95% CI = 1.13–1.56, and P = 0.001, resp.). Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs. PMID:25165692

  13. Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

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    Khaled Lasram

    2014-01-01

    Full Text Available Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.. Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, and P=0.007. Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, and P<10-3 and OR = 1.33, 95% CI = 1.13–1.56, and P=0.001, resp.. Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs.

  14. The performance of the SEPT9 gene methylation assay and a comparison with other CRC screening tests: A meta-analysis.

    Science.gov (United States)

    Song, Lele; Jia, Jia; Peng, Xiumei; Xiao, Wenhua; Li, Yuemin

    2017-06-08

    The SEPT9 gene methylation assay is the first FDA-approved blood assay for colorectal cancer (CRC) screening. Fecal immunochemical test (FIT), FIT-DNA test and CEA assay are also in vitro diagnostic (IVD) tests used in CRC screening. This meta-analysis aims to review the SEPT9 assay performance and compare it with other IVD CRC screening tests. By searching the Ovid MEDLINE, EMBASE, CBMdisc and CJFD database, 25 out of 180 studies were identified to report the SEPT9 assay performance. 2613 CRC cases and 6030 controls were included, and sensitivity and specificity were used to evaluate its performance at various algorithms. 1/3 algorithm exhibited the best sensitivity while 2/3 and 1/1 algorithm exhibited the best balance between sensitivity and specificity. The performance of the blood SEPT9 assay is superior to that of the serum protein markers and the FIT test in symptomatic population, while appeared to be less potent than FIT and FIT-DNA tests in asymptomatic population. In conclusion, 1/3 algorithm is recommended for CRC screening, and 2/3 or 1/1 algorithms are suitable for early detection for diagnostic purpose. The SEPT9 assay exhibited better performance in symptomatic population than in asymptomatic population.

  15. Association of XPC Gene Polymorphisms with Colorectal Cancer Risk in a Southern Chinese Population: A Case-Control Study and Meta-Analysis

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    Rui-Xi Hua

    2016-09-01

    Full Text Available Xeroderma pigmentosum group C (XPC is a key component of the nucleotide excision repair (NER pathway. Dysfunctional XPC protein may impair NER-mediated DNA repair capacity and further lead to genomic instability and carcinogenesis. Two common nonsynonymous polymorphisms in the XPC gene, Lys939Gln (rs2228001 A > C and Ala499Val (rs2228000 C > T, have been investigated in various types of cancer. We genotyped these two polymorphisms in 1141 cases with histologically confirmed colorectal cancer (CRC and 1173 healthy controls to explore their causative association with CRC susceptibility. Overall, no association was observed between these two variants and the risk of CRC. Our meta-analysis also confirmed a lack of overall association. Stratified analyses were performed by age, gender, smoking status, pack-year, drinking status, tumor sites, and Duke’s stages. We found that XPC Lys939Gln polymorphism was significantly associated with an increased CRC risk in subjects at 57 years of age or younger (adjusted odds ratio (OR = 1.37, 95% confidence interval (CI = 1.004–1.86, p = 0.047 and non-drinkers (adjusted OR = 1.53, 95% CI = 1.10–2.12, p = 0.011. Our results indicated that XPC Lys939Gln may be a low-penetrance CRC susceptibility polymorphism. Our findings warrant further validation.

  16. Association of rs731236 polymorphism in the vitamin D receptor gene with degenerative disc disease: evidence from a meta-analysis.

    Science.gov (United States)

    Zong, Qiang; Ni, Dongkui; Li, Lijun; Shi, Yubo

    2015-01-01

    The purpose of this study was to investigate the association between the rs731236 polymorphism in the vitamin D receptor gene and degenerative disc disease, especially in Chinese. We elaborately searched the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed and EMBASE databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. A total of 10 studies involving 1,220 cases and 1,225 controls were included in the present study. Overall, no evidence of significant risk between rs731236 polymorphism and degenerative disc disease was found in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by sample size in Chinese population show that sample size may be the primary source of heterogeneity. This meta-analysis suggested that the rs731236 polymorphism may not be associated with degenerative disc disease. However, for Asians, there existed some diversities, especially in Chinese population. Therefore, a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease.

  17. [Meta-analysis on relationship between single nucleotide polymorphism of rs2231142 in ABCG2 gene and gout in East Asian population].

    Science.gov (United States)

    Wu, Lei; He, Yao; Zhang, Di

    2015-11-01

    To systematically evaluate the association between single nucleotide polymorphism of rs2231142 genetic susceptibility and gout in East Asian population. The literature retrieval was conducted by using English databases (Medline, EMbase), Chinese databases (CNKI, Vip, Wanfang, SinaMed) and others to collect the published papers on the association between single nucleotide polymorphism of rs2231142 genetic susceptibility and gout by the end of December 2014. Meta-analysis was performed with software Stata 12.0. Nine studies were included. There were significant associations between increased risk of gout and single nucleotide polymorphism of rs2231142, the combined OR was 2.04 (95%CI: 1.82-2.28) for A allele and C allele, 1.97 (95%CI: 1.57-2.48) for CA and CC, 3.71 (95%CI: 3.07-4.47) for AA and CC. Sex and region specific subgroup analysis showed less heterogeneity. There is significant association between gout and single nucleotide polymorphism of rs2231142 in East Asian population, and A allele is a high risk gene for gout.

  18. A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

    Science.gov (United States)

    Shaik, A P; Sultana, A; Bammidi, V K; Sampathirao, K; Jamil, K

    2011-10-01

    A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

  19. Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer.

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    Fatemeh Khatami

    Full Text Available Promoter methylation in a number of tumor-suppressor genes (TSGs can play crucial roles in the development of thyroid carcinogenesis. The focus of the current meta-analysis was to determine the impact of promoter methylation of eight selected candidate TSGs on thyroid cancer and to identify the most important molecules in this carcinogenesis pathway. A comprehensive search was performed using Pub Med, Scopus, and ISI Web of Knowledge databases, and eligible studies were included. The methodological quality of the included studies was evaluated according to the Newcastle Ottawa scale table and pooled odds ratios (ORs; 95% confidence intervals (CIs were used to estimate the strength of the associations with Stata 12.0 software. Egger's and Begg's tests were applied to detect publication bias, in addition to the "Metatrim" method. A total of 55 articles were selected, and 135 genes with altered promoter methylation were found. Finally, we included eight TSGs that were found in more than four studies (RASSF1, TSHR, PTEN, SLC5A, DAPK, P16, RARβ2, and CDH1. The order of the pooled ORs for these eight TSGs from more to less significant was CDH1 (OR = 6.73, SLC5 (OR = 6.15, RASSF1 (OR = 4.16, PTEN (OR = 3.61, DAPK (OR = 3.51, P16 (OR = 3.31, TSHR (OR = 2.93, and RARβ2 (OR = 1.50. Analyses of publication bias and sensitivity confirmed that there was very little bias. Thus, our findings showed that CDH1 and SCL5A8 genes were associated with the risk of thyroid tumor genesis.

  20. Regulation of eucaryotic gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Brent, R.; Ptashne, M.S

    1989-05-23

    This patent describes a method of regulating the expression of a gene in a eucaryotic cell. The method consists of: providing in the eucaryotic cell, a peptide, derived from or substantially similar to a peptide of a procaryotic cell able to bind to DNA upstream from or within the gene, the amount of the peptide being sufficient to bind to the gene and thereby control expression of the gene.

  1. Differential Gene Expression and Aging

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    Laurent Seroude

    2002-01-01

    Full Text Available It has been established that an intricate program of gene expression controls progression through the different stages in development. The equally complex biological phenomenon known as aging is genetically determined and environmentally modulated. This review focuses on the genetic component of aging, with a special emphasis on differential gene expression. At least two genetic pathways regulating organism longevity act by modifying gene expression. Many genes are also subjected to age-dependent transcriptional regulation. Some age-related gene expression changes are prevented by caloric restriction, the most robust intervention that slows down the aging process. Manipulating the expression of some age-regulated genes can extend an organism's life span. Remarkably, the activity of many transcription regulatory elements is linked to physiological age as opposed to chronological age, indicating that orderly and tightly controlled regulatory pathways are active during aging.

  2. Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

    NARCIS (Netherlands)

    Saxena, Richa; Elbers, Clara C.; Guo, Yiran; Peter, Inga; Gaunt, Tom R.; Mega, Jessica L.; Lanktree, Matthew B.; Tare, Archana; Almoguera Castillo, Berta; Li, Yun R.; Johnson, Toby; Bruinenberg, Marcel; Gilbert-Diamond, Diane; Rajagopalan, Ramakrishnan; Voight, Benjamin F.; Balasubramanyam, Ashok; Barnard, John; Bauer, Florianne; Baumert, Jens; Bhangale, Tushar; Boehm, Bernhard O.; Braund, Peter S.; Burton, Paul R.; Chandrupatla, Hareesh R.; Clarke, Robert; Cooper-DeHoff, Rhonda M.; Crook, Errol D.; Davey-Smith, George; Day, Ian N.; de Boer, Anthonius; de Groot, Mark C. H.; Drenos, Fotios; Ferguson, Jane; Fox, Caroline S.; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Gilhuijs-Pederson, Lisa A.; Glessner, Joseph T.; Goel, Anuj; Gong, Yan; Grant, Struan F. A.; Kumari, Meena; van der Harst, Pim; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Wolffenbuttel, Bruce H. R.; Hofker, Marten H.; Asselbergs, Folkert W.; Wijmenga, Cisca

    2012-01-01

    To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and

  3. Anorexia nervosa and the Val158Met polymorphism of the COMT gene: meta-analysis and new data

    NARCIS (Netherlands)

    Brandys, Marek K.; Slof-Op't Landt, Margarita C. T.; van Elburg, Annemarie A.; Ophoff, Roel; Verduijn, Willem; Meulenbelt, Ingrid; Middeldorp, Christel M.; Boomsma, Dorret I.; van Furth, Eric F.; Slagboom, Eline; Kas, Martien J. H.; Adan, Roger A. H.

    2012-01-01

    Objectives This study aimed to test the association between the Val158Met polymorphism (rs4680) of the catechol-O-methyl transferase gene and anorexia nervosa (AN). Methods First, an association study on two cohorts (306 cases and 1009 controls from Utrecht, and 174 cases and 466 controls from

  4. The Val66Met polymorphism of the BDNF gene in anorexia nervosa: New data and a meta-analysis

    NARCIS (Netherlands)

    Brandys, Marek K.; Kas, Martien J. H.; van Elburg, Annemarie A.; Ophoff, Roel; Slof-Op't Landt, Margarita C. T.; Middeldorp, Christel M.; Boomsma, Dorret I.; van Furth, Eric F.; Slagboom, P. Eline; Adan, Roger A. H.

    2013-01-01

    Objectives. The Val66Met polymorphism (rs6265) of the BDNF gene is a non-synonymous polymorphism, previously associated with anorexia nervosa (AN). Methods. We genotyped rs6265 in 235 patients with AN and 643 controls. Furthermore, we performed a systematic review of all case-control and

  5. Plasminogen activator inhibitor-1 4G/5G gene polymorphism and coronary artery disease in the Chinese Han population: a meta-analysis.

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    Yan-yan Li

    Full Text Available BACKGROUND: The polymorphism of plasminogen activator inhibitor-1 (PAI-1 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD susceptibility, but study results are still debatable. OBJECTIVE AND METHODS: The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI was assessed by the random effect model. RESULTS: The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004. The heterogeneity test was also significant (P<0.0001. Meta-regression was performed to explore the heterogeneity source. Among the confounding factors, the heterogeneity could be explained by the publication year (P = 0.017, study region (P = 0.014, control group sample size (P = 0.011, total sample size (P = 0.011, and ratio of the case to the control group sample size (RR (P = 0.019. In a stratified analysis by the total sample size, significantly increased risk was only detected in subgroup 2 under an allelic genetic model (OR = 1.93, 95% CI = 1.09 to 3.35, P = 0.02. CONCLUSIONS: In the Chinese Han population, PAI-1 4G/5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD.

  6. Association between SLC2A9 (GLUT9) gene polymorphisms and gout susceptibility: an updated meta-analysis.

    Science.gov (United States)

    Zhang, Xu; Yang, Xiao; Wang, Mengmeng; Li, Xiaona; Xia, Qing; Xu, Shengqian; Xu, Jianhua; Cai, Guoqi; Wang, Li; Xin, Lihong; Zou, Yanfeng; Pan, Faming

    2016-08-01

    The relationship between the SLC2A9 (solute carrier family 2, member 9) gene polymorphisms and gout was still inconsistent among the individual genetic association studies. Therefore, this present research was aimed to systematically evaluate the association between SLC2A9 gene polymorphisms and gout susceptibility. Relevant studies were enrolled by searching databases systematically. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the associations. The heterogeneity between each of the studies was calculated by using the Q statistic methods, and Begg's funnel plot and Egger's tests were performed to evaluate publication bias. A total of 13 studies investigated four single nucleotide polymorphisms (SNPs) in SLC2A9 were included. In this study, we found that the allele C of rs3733591 was higher in patients than in controls in both all-pooled population [C vs. T: OR (95 % CI) = 1.432 (1.213-1.691)] and Asians-pooled population [C vs. T: OR (95 % CI) = 1.583 (1.365-1.835)]. The allele frequency C of s6449213 was lower in the gout patients than in controls in both all-pooled population and Caucasians-pooled population. Additionally, the allele frequency T of rs16890979 and the allele frequency C of rs1014290 were lower in gout patients than in controls. This study demonstrated that the genetic susceptibility for gout is associated with the SLC2A9 gene polymorphisms. Four of them except for the rs3733591 are protective SNPs in Caucasians, and rs16890979 and rs1014290 are protective SNPs in both Caucasians and Asians, while rs3733591 may be susceptibility SNP in Asians.

  7. Germline variants in the ATM gene and breast cancer susceptibility in Moroccan women: A meta-analysis

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    Chaymaa Marouf

    2017-10-01

    Full Text Available Background: The ATM gene encoding a large protein kinase is mutated in ataxia-telangiectasia (AT, an autosomale recessive disease characterized by neurological and immunological symptoms, and cancer predisposition. Previous studies suggest that heterozygous carriers of ATM mutations have an increased risk of breast cancer compared with non carriers, but the contribution of specific variants has been difficult to estimate. However, two functional ATM variants, c.7271T > G and c.1066–6T > G (IVS10–6T > G, are associated with increased risk for the development of breast cancer. Methods: To investigate the role of ATM in breast cancer susceptibility, we genotyped 163 case patients with breast cancer and 150 healthy control individuals for the c.7271T > G and c.1066–6T > G (IVS10–6T > G ATM variants using polymerase chain reaction (PCR-restriction fragment length polymorphism (RFLP analysis. Results: We did not detect the ATM c.7271T > G and c.1066–6T > G (IVS10–6T > G mutations in any of 150 healthy control individuals and 163 breast cancer patients, including 59 women diagnosed with breast cancer at an early age ( G (IVS10–6T > G mutation and the rare c.7271T > G variant are not a risk factor for developing breast cancer in the Moroccan population. Larger and/or combined association studies are needed to clarify this issue. Keywords: Breast cancers, ATM gene, Germline mutation, Genetic susceptibility, Moroccan population

  8. Developmental and environmental regulation of Aquaporin gene expression across Populus species: divergence or redundancy?

    Science.gov (United States)

    Cohen, David; Bogeat-Triboulot, Marie-Béatrice; Vialet-Chabrand, Silvère; Merret, Rémy; Courty, Pierre-Emmanuel; Moretti, Sébastien; Bizet, François; Guilliot, Agnès; Hummel, Irène

    2013-01-01

    Aquaporins (AQPs) are membrane channels belonging to the major intrinsic proteins family and are known for their ability to facilitate water movement. While in Populus trichocarpa, AQP proteins form a large family encompassing fifty-five genes, most of the experimental work focused on a few genes or subfamilies. The current work was undertaken to develop a comprehensive picture of the whole AQP gene family in Populus species by delineating gene expression domain and distinguishing responsiveness to developmental and environmental cues. Since duplication events amplified the poplar AQP family, we addressed the question of expression redundancy between gene duplicates. On these purposes, we carried a meta-analysis of all publicly available Affymetrix experiments. Our in-silico strategy controlled for previously identified biases in cross-species transcriptomics, a necessary step for any comparative transcriptomics based on multispecies design chips. Three poplar AQPs were not supported by any expression data, even in a large collection of situations (abiotic and biotic constraints, temporal oscillations and mutants). The expression of 11 AQPs was never or poorly regulated whatever the wideness of their expression domain and their expression level. Our work highlighted that PtTIP1;4 was the most responsive gene of the AQP family. A high functional divergence between gene duplicates was detected across species and in response to tested cues, except for the root-expressed PtTIP2;3/PtTIP2;4 pair exhibiting 80% convergent responses. Our meta-analysis assessed key features of aquaporin expression which had remained hidden in single experiments, such as expression wideness, response specificity and genotype and environment interactions. By consolidating expression profiles using independent experimental series, we showed that the large expansion of AQP family in poplar was accompanied with a strong divergence of gene expression, even if some cases of functional redundancy

  9. Developmental and environmental regulation of Aquaporin gene expression across Populus species: divergence or redundancy?

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    David Cohen

    Full Text Available Aquaporins (AQPs are membrane channels belonging to the major intrinsic proteins family and are known for their ability to facilitate water movement. While in Populus trichocarpa, AQP proteins form a large family encompassing fifty-five genes, most of the experimental work focused on a few genes or subfamilies. The current work was undertaken to develop a comprehensive picture of the whole AQP gene family in Populus species by delineating gene expression domain and distinguishing responsiveness to developmental and environmental cues. Since duplication events amplified the poplar AQP family, we addressed the question of expression redundancy between gene duplicates. On these purposes, we carried a meta-analysis of all publicly available Affymetrix experiments. Our in-silico strategy controlled for previously identified biases in cross-species transcriptomics, a necessary step for any comparative transcriptomics based on multispecies design chips. Three poplar AQPs were not supported by any expression data, even in a large collection of situations (abiotic and biotic constraints, temporal oscillations and mutants. The expression of 11 AQPs was never or poorly regulated whatever the wideness of their expression domain and their expression level. Our work highlighted that PtTIP1;4 was the most responsive gene of the AQP family. A high functional divergence between gene duplicates was detected across species and in response to tested cues, except for the root-expressed PtTIP2;3/PtTIP2;4 pair exhibiting 80% convergent responses. Our meta-analysis assessed key features of aquaporin expression which had remained hidden in single experiments, such as expression wideness, response specificity and genotype and environment interactions. By consolidating expression profiles using independent experimental series, we showed that the large expansion of AQP family in poplar was accompanied with a strong divergence of gene expression, even if some cases of

  10. Association between the melatonin receptor 1B gene polymorphism on the risk of type 2 diabetes, impaired glucose regulation: a meta-analysis.

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    Qing Xia

    Full Text Available BACKGROUND: Melatonin receptor 1B (MTNR1B belongs to the seven-transmembrane G protein-coupled receptor superfamily involved in insulin secretion, which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D since it was first identified as a loci associated with fasting plasma glucose level through genome wide association approach. The relationship between MTNR1B and T2D has been reported in various ethnic groups. The aim of this study was to consolidate and summarize published data on the potential of MTNR1B polymorphisms in T2D risk prediction. METHODS: PubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated. Heterogeneity and publication bias were also tested. RESULTS: A total of 23 studies involving 172,963 subjects for two common polymorphisms (rs10830963, rs1387153 on MTNR1B were included. An overall random effects per-allele OR of 1.05 (95% CI: 1.02-1.08; P<10(-4 and 1.04 (95% CI: 0.98-1.10; P = 0.20 were found for the two variants respectively. Similar results were also observed using dominant or recessive genetic model. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant results were found in Caucasians when stratified by ethnicity; while no significant associations were observed in East Asians and South Asians. Besides, we found that the rs10830963 polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. CONCLUSIONS: This meta-analysis demonstrated that the rs10830963 polymorphism is a risk factor for developing impaired glucose regulation and T2D.

  11. Association between polymorphisms in XRCC1 gene and treatment outcomes of patients with advanced gastric cancer: a systematic review and meta-analysis.

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    Zhuo Cao

    Full Text Available BACKGROUND: Many reports have shown inconsistent results on the relationship between single nucleotide polymorphisms (SNPs of X-ray repair cross complementing protein (XRCC1 gene and platinum-based chemotherapeutic efficacy. This meta-analysis aimed to summarize published data about the association between two SNPs of XRCC1 (Arg194Trp and Arg399Gln and treatment outcomes of patients with advanced gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: We retrieved the relevant articles from MEDLINE, Web of Knowledge, and the China National Knowledge Infrastructure (CNKI databases. Studies were selected according to specific inclusion and exclusion criteria. Study quality was assessed according to the guidelines outlined by Hayden, et al. and PRISMA guidelines. We estimated the odds ratio (OR for response rate versus no response after platinum-based chemotherapy. Progression-free survival (PFS and overall survival (OS were evaluated by pooled Cox proportional hazard ratios (HRs and 95% confidence intervals (CIs. We found that none of the XRCC1 Arg194Trp and Arg399Gln polymorphisms was significantly associated with tumor response. Stratified analysis by ethnicity or sensitivity analysis also showed that XRCC1 SNPs were not related with chemotherapy response. Patients with minor variant A allele were likely to have poorer 2-year survival rate than those with G/G genotype. However, in the group of 5-year follow up, there was no significant association between the A allele and OS yet. CONCLUSIONS/SIGNIFICANCE: There is no evidence to support the use of XRCC1 Arg194Trp and Arg399Gln polymorphisms as prognostic predictors of TR and PFS in gastric patients treated with platinum-based chemotherapy. The relationship between minor variant A allele and OS requires further verification.

  12. Polymorphisms in XPD gene could predict clinical outcome of platinum-based chemotherapy for non-small cell lung cancer patients: a meta-analysis of 24 studies.

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    Qin Qin

    Full Text Available OBJECTIVE: Xeroderma pigmentosum group D (XPD is an essential gene involved in the nucleotide excision repair (NER pathway. Two commonly studied single nucleotide polymorphisms (SNPs of XPD (Lys751Gln, A>C, rs13181; Asp312Asn, G>A, rs1799793 are implicated in the modulation of DNA repair capacity, thus related to the responses to platinum-based chemotherapy. Here we performed a meta-analysis to better evaluate the association between the two XPD SNPs and clinical outcome of platinum-based chemotherapy in non-small cell lung cancer (NSCLC patients. METHODS: A comprehensive search of PubMed database was conducted to identify relevant articles. Primary outcomes included objective response (i.e., complete response + partial response vs. stable disease + progressive disease, progression-free survival (PFS and overall survival (OS. The pooled and 95% confidence intervals (CIs of ORs (odds ratios and HRs (hazard ratios were estimated using the fixed or random effect model. RESULTS: Twenty-four studies were eligible according to the inclusion criteria. None of the XPD Lys751Gln/Asp312Asn polymorphisms was associated with objective response, PFS or OS in NSCLC patients treated with platinum drugs. However, in stratified analysis by ethnicity, the XPD Lys751Gln (A>C polymorphism was not significantly associated with increased response in Caucasians (OR=1.35, 95%CI=1.0-1.83, P=0.122 for heterogeneity but was associated with decreased PFS in Asians (HR=1.39, 95%CI=1.07-1.81, P=0.879 for heterogeneity. Furthermore, a statistically significant difference existed in the estimates of effect between the two ethnicities (P=0.014 for TR; PC may have inverse predictive and prognostic role in platinum-based treatment of NSCLC according to different ethnicities. Further studies are needed to validate our findings.

  13. Impact of TNF -308 G>A (rs1800629) gene polymorphism in modulation of leprosy risk: a reappraise meta-analysis of 14 case-control studies.

    Science.gov (United States)

    Areeshi, Mohammed Y; Mandal, Raju K; Dar, Sajad A; Jawed, Arshad; Wahid, Mohd; Lohani, Mohtashim; Panda, Aditya K; Mishra, Bhartendu N; Akhter, Naseem; Haque, Shafiul

    2017-10-31

    Earlier studies have shown that tumor necrosis factor ( TNF ) -308 G>A (rs1800629) gene polymorphism is implicated in the susceptibility to leprosy, but results were inconsistent. A meta-analysis of 14 studies involving 3327 leprosy cases and 3203 controls was performed to appraise the association of TNF -308 G>A polymorphism with leprosy using MEDLINE (PUBMED), EMBASE, and Google Scholar web databases. Overall, no significant association was observed in allelic (A vs. G: P =0.068; OR = 0.836, 95% CI = 0.689-1.013), homozygous (AA vs. GG: P =0.394; OR = 0.810, 95% CI = 0.499-1.315), heterozygous (GA vs. GG: P =0.059; OR = 0.780, 95% CI = 0.603-1.010), dominant (AA + GA vs. GG: P =0.067; OR = 0.797, 95% CI = 0.625-1.016), and recessive (AA vs. GG + GA: P =0.594; OR = 0.877, 95% CI = 0.542- 1.420) genetic models. Subgroup analysis showed no association in Asians. Whereas, reduced risk was found in allelic contrast (A vs. G: P =0.014; OR = 0.832, 95% CI = 0.718-0.963) and dominant models (AA + GA vs. GG: P =0.004; OR = 0.790, 95% CI = 0.673-0.928) of the mixed population. TNF -308 G>A polymorphism is not associated with leprosy risk in the overall population. However, subgroup analysis demonstrated protective effect of the said polymorphism in leprosy risk in the Latin American population, but showed no association in the Asians. © 2017 The Author(s).

  14. The association of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1 K121Q gene polymorphism with the risk of type 2 diabetes mellitus in European, American, and African populations: a meta-analysis

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    Jonny Karunia Fajar

    2016-07-01

    Full Text Available Introduction: Several studies regarding the association of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1 K121Q gene polymorphism with the risk of type 2 diabetes mellitus (T2DM showed inconsistent results. This study aimed to investigate the association of ENPP1 K121Q gene polymorphism with T2DM risk using meta-analysis. The study was limited to the American, European, and African populations.Methods: PubMed and Embase databases were searched for eligible publications. The following information was extracted from each study: name of first author, publication year, country of origin, sample size of cases and controls, and size of each allele. The combined odds ratios (ORs and 95% confidence intervals (95% CIs for the association between ENPP1 K121Q gene polymorphism and T2DM risk were assessed using random or fixed effect model. A comprehensive meta-analysis (CMA 2.0 was used to analyze the data.Results: Nineteen studies (17717 cases/28022 controls on the association between ENPP1 K121Q gene polymorphism and T2DM risk were included in this meta-analysis. The results indicated that the ENPP1 K121Q gene polymorphism was associated with increased T2DM risk (Q vs. K genetic model, OR 95% CI = 1.11 [1.02–1.22], p = 0.014; QQ vs. KK + KQ, OR 95% CI = 1.14 [1.01–1.23], p = 0.039 and decreased T2DM risk (K vs. Q, OR 95% CI = 0.90 [0.82–1.00], p = 0.014; KK vs. KQ + QQ, OR 95% CI = 0.89 [0.80–0.98], p = 0.024.Conclusions: The results indicate that the ENPP1 K121Q gene polymorphism is associated with the risk of T2DM in the American, European, and African populations.

  15. Association between polymorphisms in the coagulation factor VII gene and coronary heart disease risk in different ethnicities: a meta-analysis

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    Mo Xingbo

    2011-08-01

    Full Text Available Abstract Background Previous studies have examined the association between polymorphisms in the coagulation factor VII gene and the risk of coronary heart disease (CHD, but those studies have been inconclusive. This study was conducted to assess the associations between these polymorphisms and CHD and evaluated the associations in different ethnicities. Methods Literature-based searching was conducted to collect data and two methods, namely fixed-effects and random-effects, were performed to pool the odds ratio (OR, together with the 95% confidence interval (CI. Publication bias and between-study heterogeneity were also examined. Results Thirty-nine case-control studies of the three polymorphisms, R353Q (rs6046, HVR4 and -323Ins10 (rs36208070 in factor VII gene and CHD were enrolled in this meta-analysis, including 9,151 cases of CHD and 14,099 controls for R353Q, 2,863 cases and 2,727 controls for HVR4, and 2,862 cases and 4,240 controls for -323Ins10. Significant association was only found in Asian population for R353Q (Q vs R, with pooled OR of 0.70(95%CI: 0.55, 0.90. For the -323Ins10 polymorphism (10 vs 0, we found significant associations in both Asian and European populations, with pooled ORs of 0.74(95%CI: 0.61, 0.88 and 0.63(95%CI: 0.53, 0.74, respectively. Marginal significant association was found between HVR4 (H7 vs H5+H6 and CHD (OR = 0.88, 95% CI: 0.78, 1.00. There was no evidence of publication bias, but between-study heterogeneity was found in the analyses. Conclusions The -323Ins10 polymorphism in factor VII gene is significantly associated with CHD in both Asian and European populations, while R353Q polymorphism showed trend for association with CHD in Asians. Lack of association was found for HVR4 polymorphism. Further studies are needed to confirm the association, especially for -323Ins10 polymorphism.

  16. Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation.

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    Alexandra Dumitriu

    2012-06-01

    Full Text Available Parkinson disease (PD is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9 of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1 transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR-significant group of genes (177 genes covered by 189 probes, suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs selected from a recent meta-analysis of PD genome-wide association studies (GWAS were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression-SNP (eSNP analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK gene and a probe in the spermine oxidase (SMOX gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD-relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms.

  17. A novel joint analysis framework improves identification of differentially expressed genes in cross disease transcriptomic analysis

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    Wenyi Qin

    2018-02-01

    Full Text Available Abstract Motivation Detecting differentially expressed (DE genes between disease and normal control group is one of the most common analyses in genome-wide transcriptomic data. Since most studies don’t have a lot of samples, researchers have used meta-analysis to group different datasets for the same disease. Even then, in many cases the statistical power is still not enough. Taking into account the fact that many diseases share the same disease genes, it is desirable to design a statistical framework that can identify diseases’ common and specific DE genes simultaneously to improve the identification power. Results We developed a novel empirical Bayes based mixture model to identify DE genes in specific study by leveraging the shared information across multiple different disease expression data sets. The effectiveness of joint analysis was demonstrated through comprehensive simulation studies and two real data applications. The simulation results showed that our method consistently outperformed single data set analysis and two other meta-analysis methods in identification power. In real data analysis, overall our method demonstrated better identification power in detecting DE genes and prioritized more disease related genes and disease related pathways than single data set analysis. Over 150% more disease related genes are identified by our method in application to Huntington’s disease. We expect that our method would provide researchers a new way of utilizing available data sets from different diseases when sample size of the focused disease is limited.

  18. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...

  19. Correction of gene expression data

    DEFF Research Database (Denmark)

    Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin

    2014-01-01

    This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies....... For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce...

  20. EGFR gene copy number as a prognostic marker in colorectal cancer patients treated with cetuximab or panitumumab: a systematic review and meta analysis.

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    Zheng Jiang

    Full Text Available The epidermal growth factor receptor (EGFR gene copy number (GCN has been previously demonstrated to correlate with the clinical outcome of colorectal cancer (CRC treated with anti-EGFR monoclonal antibodies (mAbs, although it remains controversial. We conducted a systematic review and meta-analysis to assess EGFR GCN as a potential biomarker of survival for patients with advanced CRC receiving treatment with anti-EGFR mAbs.We systematically identified articles investigating EGFR GCN by fluorescent or chromogenic in situ hybridization or other detection techniques in patients with metastatic CRC treated with panitumumab or cetuximab, (last search: 10 August 2012. Eligible studies had to report on overall survival (OS, progression-free survival (PFS or time-to-progression (TTP, stratified by EGFR GCN. Summary hazard ratios (HRs were calculated using random-effects models.Among 13 identified studies, 10 (776 patients, 302 with increased GCN, 8 (893 patients, 282 with increased GCN and 3 (149 patients, 66 with increased GCN were eligible for the OS, PFS and TTP meta-analyses, respectively. Increased EGFR GCN was associated with increased OS (HR = 0.62; 95% CI 0.50-0.77; P<0.001, PFS (HR = 0.65; 95% CI 0.47-0.89; P = 0.008 but not TTP (HR = 0.71; 95% CI 0.44-1.14; P = 0.157. It was also shown that EGFR GCN is independent of other factors such as KRAS status. Among those populations received second-line or higher treatment, increased EGFR GCN was strongly associated with improved survival (for OS, HR = 0.60; 95% CI 0.47-0.75; P<0.001; for PFS, HR = 0.59; 95% CI 0.47-0.75; P<0.001, whereas it did not influence survival in patients that received first-line therapy.Among the anti-EGFR-treated patients, increased EGFR GCN appears to be associated with improved survival outcomes. The effect on survival appears to be related to patients receiving the line of treatment.

  1. Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases

    Science.gov (United States)

    Wang, Lan; Wu, Long-Fei; Lu, Xin; Mo, Xing-Bo; Tang, Zai-Xiang; Lei, Shu-Feng; Deng, Fei-Yan

    2015-01-01

    Objective Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested. Methods We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis. Results We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation. Conclusion The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases. PMID:26352601

  2. Meta-Analysis of Aedes aegypti Expression Datasets: Comparing Virus Infection and Blood-Fed Transcriptomes to Identify Markers of Virus Presence

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    Kiyoshi Ferreira Fukutani

    2018-01-01

    Full Text Available The mosquito Aedes aegypti (L. is vector of several arboviruses including dengue, yellow fever, chikungunya, and more recently zika. Previous transcriptomic studies have been performed to elucidate altered pathways in response to viral infection. However, the intrinsic coupling between alimentation and infection were unappreciated in these studies. Feeding is required for the initial mosquito contact with the virus and these events are highly dependent. Addressing this relationship, we reinterrogated datasets of virus-infected mosquitoes with two different diet schemes (fed and unfed mosquitoes, evaluating the metabolic cross-talk during both processes. We constructed coexpression networks with the differentially expressed genes of these comparison: virus-infected versus blood-fed mosquitoes and virus-infected versus unfed mosquitoes. Our analysis identified one module with 110 genes that correlated with infection status (representing ~0.7% of the A. aegypti genome. Furthermore, we performed a machine-learning approach and summarized the infection status using only four genes (AAEL012128, AAEL014210, AAEL002477, and AAEL005350. While three of the four genes were annotated as hypothetical proteins, AAEL012128 gene is a membrane amino acid transporter correlated with viral envelope binding. This gene alone is able to discriminate all infected samples and thus should have a key role to discriminate viral infection in the A. aegypti mosquito. Moreover, validation using external datasets found this gene as differentially expressed in four transcriptomic experiments. Therefore, these genes may serve as a proxy of viral infection in the mosquito and the others 106 identified genes provides a framework to future studies.

  3. Rs7574865 polymorphism in signal transducers and activators of transcription 4 gene and rheumatoid arthritis: an updated meta-analysis of 28 case-control comparisons.

    Science.gov (United States)

    Gu, EnPeng; Lu, Jun; Xing, Dan; Chen, XingRan; Xie, HaiBo; Liang, JinQian; Li, Lin

    2015-01-01

    The objective of the present meta-analysis was to investigate whether the combined evidence shows an association between the STAT4 rs7574865 polymorphism and RA. A systematic search of all relevant studies published through April 2013 was conducted using MEDLINE, EMBASE, OVID, and ScienceDirect. The observational studies that were related to an association between the STAT4 rs7574865 polymorphism and RA were identified. The association between the STAT4 rs7574865 polymorphism and RA susceptibility was assessed using genetic models. Seventeen case-control studies with a total of 28 comparisons (25 300 RA patients and 26 326 controls) met the inclusion criteria. A meta-analysis was conducted for genotype TT versus GT+GG, GT+TT versus GG, TT versus GG and T-allele. The meta-analysis showed an association between RA and the STAT4 rs7574865 TT genotype, GT+TT genotype and T-allele in all subjects. Stratification of RA patients according to ethnic group showed that the TT genotype, GT+TT genotype and T-allele were significantly associated with RA in Europeans, Asians, Africans and Latin Americans. A subgroup analysis according to the absence or presence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies revealed that the association between the STAT4 rs7574865 polymorphism and RA may be independent of the presence of RF and anti-CCP antibodies. This meta-analysis demonstrated that the STAT4 rs7574865 polymorphism confers susceptibility to RA in major ethnic groups. The association may not be dependent on the presence of RF and anti-CCP antibodies. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

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

    Science.gov (United States)

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

    2018-01-01

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

  5. Meta-analysis of the effect of overexpression of C-repeat/dehydration-responsive element binding family genes on temperature stress tolerance and related responses

    Science.gov (United States)

    C-repeat/dehydration-responsive element binding proteins are transcription factors that play a critical role in plant response to temperature stress. Over-expression of CBF/DREB genes has been demonstrated to enhance temperature stress tolerance. A series of physiological and biochemical modificat...

  6. Identifying novel glioma associated pathways based on systems biology level meta-analysis.

    Science.gov (United States)

    Hu, Yangfan; Li, Jinquan; Yan, Wenying; Chen, Jiajia; Li, Yin; Hu, Guang; Shen, Bairong

    2013-01-01

    With recent advances in microarray technology, including genomics, proteomics, and metabolomics, it brings a great challenge for integrating this "-omics" data to analysis complex disease. Glioma is an extremely aggressive and lethal form of brain tumor, and thus the study of the molecule mechanism underlying glioma remains very important. To date, most studies focus on detecting the differentially expressed genes in glioma. However, the meta-analysis for pathway analysis based on multiple microarray datasets has not been systematically pursued. In this study, we therefore developed a systems biology based approach by integrating three types of omics data to identify common pathways in glioma. Firstly, the meta-analysis has been performed to study the overlapping of signatures at different levels based on the microarray gene expression data of glioma. Among these gene expression datasets, 12 pathways were found in GeneGO database that shared by four stages. Then, microRNA expression profiles and ChIP-seq data were integrated for the further pathway enrichment analysis. As a result, we suggest 5 of these pathways could be served as putative pathways in glioma. Among them, the pathway of TGF-beta-dependent induction of EMT via SMAD is of particular importance. Our results demonstrate that the meta-analysis based on systems biology level provide a more useful approach to study the molecule mechanism of complex disease. The integration of different types of omics data, including gene expression microarrays, microRNA and ChIP-seq data, suggest some common pathways correlated with glioma. These findings will offer useful potential candidates for targeted therapeutic intervention of glioma.

  7. Transgenic Arabidopsis Gene Expression System

    Science.gov (United States)

    Ferl, Robert; Paul, Anna-Lisa

    2009-01-01

    The Transgenic Arabidopsis Gene Expression System (TAGES) investigation is one in a pair of investigations that use the Advanced Biological Research System (ABRS) facility. TAGES uses Arabidopsis thaliana, thale cress, with sensor promoter-reporter gene constructs that render the plants as biomonitors (an organism used to determine the quality of the surrounding environment) of their environment using real-time nondestructive Green Fluorescent Protein (GFP) imagery and traditional postflight analyses.

  8. Human papillomavirus gene expression

    International Nuclear Information System (INIS)

    Chow, L.T.; Hirochika, H.; Nasseri, M.; Stoler, M.H.; Wolinsky, S.M.; Chin, M.T.; Hirochika, R.; Arvan, D.S.; Broker, T.R.

    1987-01-01

    To determine the role of tissue differentiation on expression of each of the papillomavirus mRNA species identified by electron microscopy, the authors prepared exon-specific RNA probes that could distinguish the alternatively spliced mRNA species. Radioactively labeled single-stranded RNA probes were generated from a dual promoter vector system and individually hybridized to adjacent serial sections of formalin-fixed, paraffin-embedded biopsies of condylomata. Autoradiography showed that each of the message species had a characteristic tissue distribution and relative abundance. The authors have characterized a portion of the regulatory network of the HPVs by showing that the E2 ORF encodes a trans-acting enhancer-stimulating protein, as it does in BPV-1 (Spalholz et al. 1985). The HPV-11 enhancer was mapped to a 150-bp tract near the 3' end of the URR. Portions of this region are duplicated in some aggressive strains of HPV-6 (Boshart and zur Hausen 1986; Rando et al. 1986). To test the possible biological relevance of these duplications, they cloned tandem arrays of the enhancer and demonstrated, using a chloramphenicol acetyltransferase (CAT) assay, that they led to dramatically increased transcription proportional to copy number. Using the CAT assays, the authors found that the E2 proteins of several papillomavirus types can cross-stimulate the enhancers of most other types. This suggests that prior infection of a tissue with one papillomavirus type may provide a helper effect for superinfection and might account fo the HPV-6/HPV-16 coinfections in condylomata that they have observed

  9. Homeobox gene expression in Brachiopoda

    DEFF Research Database (Denmark)

    Altenburger, Andreas; Martinez, Pedro; Wanninger, Andreas

    2011-01-01

    (ectoderm) specification with co-opted functions in notochord formation in chordates and left/right determination in ambulacrarians and vertebrates. The caudal ortholog, TtrCdx, is first expressed in the ectoderm of the gastrulating embryo in the posterior region of the blastopore. Its expression stays......The molecular control that underlies brachiopod ontogeny is largely unknown. In order to contribute to this issue we analyzed the expression pattern of two homeobox containing genes, Not and Cdx, during development of the rhynchonelliform (i.e., articulate) brachiopod Terebratalia transversa...... completion of larval development, which is marked by a three-lobed body with larval setae. Expression starts at gastrulation in two areas lateral to the blastopore and subsequently extends over the animal pole of the gastrula. With elongation of the gastrula, expression at the animal pole narrows to a small...

  10. Association of presence/absence and on/off patterns of Helicobacter pylori oipA gene with peptic ulcer disease and gastric cancer risks: a meta-analysis.

    Science.gov (United States)

    Liu, Jingwei; He, Caiyun; Chen, Moye; Wang, Zhenning; Xing, Chengzhong; Yuan, Yuan

    2013-11-20

    There are increasing studies examining the relationship between the status of H. pylori oipA gene and peptic ulcer disease (PUD) and gastric cancer (GC) but the results turn out to be controversial. We attempted to clarify whether oipA gene status is linked with PUD and/or GC risks. A systematically literature search was performed through four electronic databases. According to the specific inclusion and exclusion criteria, seven articles were ultimately available for the meta-analysis of oipA presence/absence with PUD and GC, and eleven articles were included for the meta-analysis of oipA on/off status with PUD and GC. For the on/off functional status analysis of oipA gene, the "on" status showed significant associations with increased risks of PUD (OR = 3.97, 95% CI: 2.89, 5.45; P gastritis and functional dyspepsia controls. Results of the homogeneity test indicated different effects of oipA "on" status on PUD risk between children and adult subgroups and on GC risk between PCR-sequencing and immunoblot subgroups. For the presence/absence analysis of oipA gene, we found null association of the presence of oipA gene with the risks of PUD (OR = 1.93, 95% CI: 0.60, 6.25; P = 0.278) and GC (OR = 2.09, 95% CI: 0.51, 8.66; P = 0.308) compared with gastritis and functional dyspepsia controls. To be concluded, when oipA exists, the functional "on" status of this gene showed association with increased risks for PUD and GC compared with gastritis and FD controls. However, merely investigating the presence/absence of oipA would overlook the importance of its functional on/off status and would not be reliable to predict risks of PUD and GC. Further large-scale and well-designed studies concerning on/off status of oipA are required to confirm our meta-analysis results.

  11. The effect and safety of monoclonal antibodies to calcitonin gene-related peptide and its receptor on migraine: a systematic review and meta-analysis.

    Science.gov (United States)

    Hou, Min; Xing, Haiyan; Cai, Yongqing; Li, Bin; Wang, Xianfeng; Li, Pan; Hu, Xiaolin; Chen, Jianhong

    2017-12-01

    Migraine has been recognized as one of the leading causes of disability in the 2013 Global Burden of Disease Study and seriously affects the quality of patients' life, current treatment options are not ideal. Monoclonal antibodies to calcitonin gene-related peptide and its receptor (CGRP-mAbs) appear more promising for migraine because of considerably better effect and safety profiles. The objective of this study is to systematically assess the clinical efficacy and safety of CGRP-mAbs for migraine therapy. A systematic literature search in PubMed, Cochrane Library and Baidu Scholar was performed to identify randomized controlled trials (RCTs), which compared the effect and safety of CGRP-mAbs with placebo on migraine. Regarding the efficacy, the reduction of monthly migraine days from baseline to weeks 1-4, 5-8, and 9-12; responder rates were extracted as the outcome measures of the effects of CGRP-mAbs. Regarding the safety, total adverse events, the main adverse events, and other adverse events were evaluated. We found significant reduction of monthly migraine days in CGRP-mAbs vs. placebo (weeks 1-4: SMD -0.49, 95% CI -0.61 to -0.36; weeks 5-8: SMD -0.43, 95% CI -0.56 to -0.30; weeks 9-12: SMD -0.37, 95% CI -0.49 to -0.24). 50% and 75% responder rates (OR 2.59, 95% CI 1.99 to 3.37; and OR 2.91, 95% CI 2.06 to 4.10) were significantly increased compared with placebo. There was no significant difference in total adverse events (OR 1.17, 95% CI 0.91 to 1.51), and the main adverse events including upper respiratory tract infection (OR 1.44, 95% CI 0.82 to 2.55), nasopharyngitis (OR 0.59, 95% CI 0.30 to 1.16), nausea (OR 0.61, 95% CI 0.29 to 1.32), injection-site pain (OR 1.73, 95% CI 0.95 to 3.16) and back pain (OR 0.97, 95% CI 0.49 to 1.90) were not obviously changed compared with placebo control, but the results showed significant increase of dizziness in CGRP-mAbs vs. placebo (OR 3.22, 95% CI 1.09 to 9.45). This meta-analysis suggests that CGRP-mAbs are

  12. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer's Disease Affected Brain Regions.

    Directory of Open Access Journals (Sweden)

    Nisha Puthiyedth

    Full Text Available Alzheimer's disease (AD is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation.The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD from the Entorhinal Cortex (EC, Hippocampus (HIP, Middle temporal gyrus (MTG, Posterior cingulate cortex (PC, Superior frontal gyrus (SFG and visual cortex (VCX brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets.We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD. In addition, we

  13. Vascular Gene Expression: A Hypothesis

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    Angélica Concepción eMartínez-Navarro

    2013-07-01

    Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

  14. Neighboring Genes Show Correlated Evolution in Gene Expression

    Science.gov (United States)

    Ghanbarian, Avazeh T.; Hurst, Laurence D.

    2015-01-01

    When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

  15. Integrative sparse principal component analysis of gene expression data.

    Science.gov (United States)

    Liu, Mengque; Fan, Xinyan; Fang, Kuangnan; Zhang, Qingzhao; Ma, Shuangge

    2017-12-01

    In the analysis of gene expression data, dimension reduction techniques have been extensively adopted. The most popular one is perhaps the PCA (principal component analysis). To generate more reliable and more interpretable results, the SPCA (sparse PCA) technique has been developed. With the "small sample size, high dimensionality" characteristic of gene expression data, the analysis results generated from a single dataset are often unsatisfactory. Under contexts other than dimension reduction, integrative analysis techniques, which jointly analyze the raw data of multiple independent datasets, have been developed and shown to outperform "classic" meta-analysis and other multidatasets techniques and single-dataset analysis. In this study, we conduct integrative analysis by developing the iSPCA (integrative SPCA) method. iSPCA achieves the selection and estimation of sparse loadings using a group penalty. To take advantage of the similarity across datasets and generate more accurate results, we further impose contrasted penalties. Different penalties are proposed to accommodate different data conditions. Extensive simulations show that iSPCA outperforms the alternatives under a wide spectrum of settings. The analysis of breast cancer and pancreatic cancer data further shows iSPCA's satisfactory performance. © 2017 WILEY PERIODICALS, INC.

  16. Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Verena Jabs

    Full Text Available Non-small cell lung cancer (NSCLC represents a genomically unstable cancer type with extensive copy number aberrations. The relationship of gene copy number alterations and subsequent mRNA levels has only fragmentarily been described. The aim of this study was to conduct a genome-wide analysis of gene copy number gains and corresponding gene expression levels in a clinically well annotated NSCLC patient cohort (n = 190 and their association with survival. While more than half of all analyzed gene copy number-gene expression pairs showed statistically significant correlations (10,296 of 18,756 genes, high correlations, with a correlation coefficient >0.7, were obtained only in a subset of 301 genes (1.6%, including KRAS, EGFR and MDM2. Higher correlation coefficients were associated with higher copy number and expression levels. Strong correlations were frequently based on few tumors with high copy number gains and correspondingly increased mRNA expression. Among the highly correlating genes, GO groups associated with posttranslational protein modifications were particularly frequent, including ubiquitination and neddylation. In a meta-analysis including 1,779 patients we found that survival associated genes were overrepresented among highly correlating genes (61 of the 301 highly correlating genes, FDR adjusted p<0.05. Among them are the chaperone CCT2, the core complex protein NUP107 and the ubiquitination and neddylation associated protein CAND1. In conclusion, in a comprehensive analysis we described a distinct set of highly correlating genes. These genes were found to be overrepresented among survival-associated genes based on gene expression in a large collection of publicly available datasets.

  17. Gene expression profile of pulpitis.

    Science.gov (United States)

    Galicia, J C; Henson, B R; Parker, J S; Khan, A A

    2016-06-01

    The cost, prevalence and pain associated with endodontic disease necessitate an understanding of the fundamental molecular aspects of its pathogenesis. This study was aimed to identify the genetic contributors to pulpal pain and inflammation. Inflamed pulps were collected from patients diagnosed with irreversible pulpitis (n=20). Normal pulps from teeth extracted for various reasons served as controls (n=20). Pain level was assessed using a visual analog scale (VAS). Genome-wide microarray analysis was performed using Affymetrix GeneTitan Multichannel Instrument. The difference in gene expression levels were determined by the significance analysis of microarray program using a false discovery rate (q-value) of 5%. Genes involved in immune response, cytokine-cytokine receptor interaction and signaling, integrin cell surface interactions, and others were expressed at relatively higher levels in the pulpitis group. Moreover, several genes known to modulate pain and inflammation showed differential expression in asymptomatic and mild pain patients (⩾30 mm on VAS) compared with those with moderate to severe pain. This exploratory study provides a molecular basis for the clinical diagnosis of pulpitis. With an enhanced understanding of pulpal inflammation, future studies on treatment and management of pulpitis and on pain associated with it can have a biological reference to bridge treatment strategies with pulpal biology.

  18. Association between platelet glycoprotein Ia C807T gene polymorphism and ischemic stroke: a meta-analysis in a separate ethnic group.

    Science.gov (United States)

    Huang, Xiao-Yun; Fu, Wen-Jin; Mei, Zhi-Zhong; Yu, Ying-Li; Huang, Yi-Hong; Lin, Han; Chen, Jian-Jun; Wang, Ming-Xia; Guan, Shao-Bing; Fang, Hao-Wei

    2017-11-30

    Many studies have been examined the association of platelet glycoprotein (GP) Ia C807T polymorphism with ischemic stroke (IS) susceptibility. However, the results of these studies are inconsistent. To further assess the effects of GP Ia C807T polymorphism on the risk of IS, a meta-analysis was performed in a separate ethnic group. Relevant studies were identified using PubMed and Chinese databases through January 2017. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. Finally, 13 studies contained 2438 IS cases and 2308 controls included. In the total analyses, a significantly elevated risk of IS was associated with all variants of GP Ia C807T in the Chinese population (T vs C: OR = 1.24, 95% CI = 1.09-1.40; TT vs CC: OR = 1.59, 95% CI = 1.17-2.15; TT and CT combined vs CC: OR = 1.32, 95% CI = 1.09-1.59; TT vs CC and CT: OR = 1.35, 95% CI = 1.04-1.76). In the subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han and in South China. This meta-analysis provides the evidence that GP Ia C807T polymorphism may contribute to the IS development in the Chinese population, especially in South China, and further studies in other ethic groups are required for definite conclusions.

  19. O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

    International Nuclear Information System (INIS)

    Brell, Marta; Ibáñez, Javier; Tortosa, Avelina

    2011-01-01

    The DNA repair protein O 6 -Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably

  20. O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Ibáñez Javier

    2011-01-01

    Full Text Available Abstract Background The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP the most commonly used for promoter methylation study, while immunohistochemistry (IHC has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. Methods A computer-aided search of MEDLINE (1950-October 2009, EBSCO (1966-October 2009 and EMBASE (1974-October 2009 was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Results Of 254 studies identified as eligible for full-text review, 52 (20.5% met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Conclusions Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.

  1. [Correlation between polymorphisms in the coagulation factor VII gene hypervariable region 4 site and the risk of coronary heart disease in population with different ethnic backgrounds: a Meta-analysis].

    Science.gov (United States)

    Wang, Li-li; Ma, Bin; Qian, Dun; Pang, Jun; Yao, Ya-li

    2013-12-01

    To assess the correlation between polymorphisms in the coagulation factor VII (F VII)gene hypervariable region 4 (HVR4)site and risk related to coronary heart disease (CHD)in different ethnic populations, especially the Asian populations. Publications up to April 2013, from CBM, CNKI, Wanfang Database,VIP, PubMed, Cochrane Library and Embase were searched to collect data from case-control studies related to F VII gene HVR4 site and CHD in populations from different ethnicities. Quality of studies was evaluated, available data extracted and both RevMan 5.1 and Stata 11.0 softwares were used for Meta-analysis. Fifteen case-control studies were included, involving 3167 cases with CHD group and 3168 cases in the control group. on this Meta-analysis showed that:a)polymorphism of the F VII gene HVR4 site H7/H6+H5 and CHD, b)H7H7/H6H6 + H7H6 and CHD were both slightly correlated between people with different ethnic backgrounds. However, the H6 allele versus H7+H5 allele and CHD showed different results-a high correlation seen in different ethnic groups. H5 allele versus H6+H7 allele and CHD did not appear significant difference(OR = 1.20, 95%CI:0.76-1.90, P = 0.43). Both F VII gene HVR4 polymorphisms H7 allele and the H7H7 genotype might have served as protective factors for CHD in different ethnic groups, H6 allele might serve as a risk factor for CHD, but H5 allele was likely not to be associated with CHD in different ethnic groups.

  2. Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene

    Science.gov (United States)

    Ludwig, Kerstin U.; Ahmed, Syeda Tasnim; Böhmer, Anne C.; Sangani, Nasim Bahram; Varghese, Sheryil; Klamt, Johanna; Schuenke, Hannah; Gültepe, Pinar; Hofmann, Andrea; Rubini, Michele; Aldhorae, Khalid Ahmed; Steegers-Theunissen, Regine P.; Rojas-Martinez, Augusto; Reiter, Rudolf; Borck, Guntram; Knapp, Michael; Nakatomi, Mitsushiro; Graf, Daniel; Mangold, Elisabeth; Peters, Heiko

    2016-01-01

    Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10−14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32–1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94–1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47–9.61, Pdifflip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions. PMID:26968009

  3. Using gene expression noise to understand gene regulation

    NARCIS (Netherlands)

    Munsky, B.; Neuert, G.; van Oudenaarden, A.

    2012-01-01

    Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a

  4. Meta-analysis of association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene and diabetic retinopathy in Caucasians and Asians.

    Science.gov (United States)

    Ma, Jinlan; Li, Yan; Zhou, Fang; Xu, Xiaoyi; Guo, Gang; Qu, Yi

    2012-01-01

    The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) gene is reported to be associated with diabetes. However, the gene's association with diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) has been investigated in numerous epidemiologic studies with controversial results. This meta-analysis aimed to collectively assess the association of the Pro12Ala polymorphism with DR in T2DM. An electronic literature search was conducted on PubMed, ISI Web of Knowledge, EMBASE, and the China National Knowledge Internet. A dominant model [(Pro/Ala +Ala/Ala) versus Pro/Pro] was used to ensure adequate statistical power. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effect model. Potential sources of heterogeneity and bias were explored. This meta-analysis included genotype data from 2,720 cases with DR and 2,450 controls free of DR from eight eligible publications. The results showed the Ala allele had a protective effect on DR in T2DM (OR=0.81; 95% CI: 0.68-0.98, p=0.03). There was no significant evidence against homogeneity (I(2)=46%, P(heterogeneity)=0.07). The sensitivity analysis showed a robust association of the Pro12Ala polymorphism with DR in T2DM after a study involving Caucasians that presented a big effect on heterogeneity (OR=0.75; 95% CI: 0.62-0.91, p=0.003) was excluded. Possible ethnic differences in the association of the Pro12Ala single nucleotide polymorphism and DR were demonstrated; a significant association was illustrated in the Caucasian subgroup (OR=0.74; 95% CI: 0.59-0.94, p=0.01) but was not found in the Asian subgroup (OR=0.77; 95% CI: 0.55-1.07, p=0.12). No publication bias was observed. This meta-analysis suggested a significant association exists between the Pro12Ala polymorphism and DR in T2DM with ethnic differences. The Ala allele had a significant protective effect against DR in T2DM.

  5. A constructive approach to gene expression dynamics

    International Nuclear Information System (INIS)

    Ochiai, T.; Nacher, J.C.; Akutsu, T.

    2004-01-01

    Recently, experiments on mRNA abundance (gene expression) have revealed that gene expression shows a stationary organization described by a scale-free distribution. Here we propose a constructive approach to gene expression dynamics which restores the scale-free exponent and describes the intermediate state dynamics. This approach requires only one assumption: Markov property

  6. Hydropower externalities: a meta analysis

    NARCIS (Netherlands)

    Mattmann, M.; Logar, I.; Brouwer, R.

    2016-01-01

    This paper presents a meta-analysis of existing research related to the economic valuation of the external effects of hydropower. A database consisting of 81 observations derived from 29 studies valuing the non-market impacts of hydropower electricity generation is constructed with the main aim to

  7. Causal Meta-Analysis : Methodology and Applications

    NARCIS (Netherlands)

    Bax, L.J.

    2009-01-01

    Meta-analysis is a statistical method to summarize research data from multiple studies in a quantitative manner. This dissertation addresses a number of methodological topics in causal meta-analysis and reports the development and validation of meta-analysis software. In the first (methodological)

  8. a meta-analysis.

    African Journals Online (AJOL)

    Relationship between IL-10 gene -819C/T polymorphism and the risk of inflammatory bowel ... African Health Sciences Vol 16 Issue 3, September 2016. 866 .... Fernandez et al. 2005 ..... Andersen V, Ernst A, Christensen J,et al.The poly-.

  9. Modulation of gene expression made easy

    DEFF Research Database (Denmark)

    Solem, Christian; Jensen, Peter Ruhdal

    2002-01-01

    A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example...... that the method can be applied to modulating the expression of native genes on the chromosome. We constructed a series of strains in which the expression of the las operon, containing the genes pfk, pyk, and ldh, was modulated by integrating a truncated copy of the pfk gene. Importantly, the modulation affected...

  10. Synthetic promoter libraries- tuning of gene expression

    DEFF Research Database (Denmark)

    Hammer, Karin; Mijakovic, Ivan; Jensen, Peter Ruhdal

    2006-01-01

    knockout and strong overexpression. However, applications such as metabolic optimization and control analysis necessitate a continuous set of expression levels with only slight increments in strength to cover a specific window around the wildtype expression level of the studied gene; this requirement can......The study of gene function often requires changing the expression of a gene and evaluating the consequences. In principle, the expression of any given gene can be modulated in a quasi-continuum of discrete expression levels but the traditional approaches are usually limited to two extremes: gene...

  11. Association of gene polymorphism of SDF1(CXCR12 with susceptibility to HIV-1 infection and AIDS disease progression: A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jiwei Ding

    Full Text Available Genetic polymorphism of viral receptors is relevant to risks of HIV-1 infection, while it is still under debated whether the polymorphism of SDF1, a unique ligand for HIV-1 coreceptor CXCR4, is associated with HIV susceptibility and AIDS disease progression. Therefore, we provided an updated quantitative assessment by meta-analysis from 16 case-control and 7 cohort studies.Articles reporting the relationship between SDF1 polymorphism and HIV susceptibility or AIDS progression were retrieved from PubMed, Embase and Ovid electronic databases up to Apr 2017. Data were pooled by odds ratios (ORs for HIV-1 infection with 95% confidence intervals (CIs and summary relative hazards (RHs for AIDS progression with 95% CIs using 1987 Center for Disease Control (CDC case definition of AIDS (CDC87 and 1993 Center for Disease Control (CDC case definition of AIDS (CDC93 and death as endpoints.As a result, 16 studies regarding susceptibility to HIV-1 infection with 2803 HIV-infected patients and 3697 healthy individuals and 7 studies regarding disease progression with 4239 subjects were included in the meta-analysis. For risks of infection, no evidences indicated SDF1 polymorphism was associated with the risk of HIV-1 infection in all genetic models (recessive model: OR = 0.94, 95% Cl: 0.75-1.17; homozygous model: OR = 0.89, 95% Cl: 0.70-1.15; heterozygous model: OR = 1.06, 95% Cl: 0.83-1.35; allele model: OR = 0.95, 95% Cl: 0.79-1.13, Furthermore, we failed to find an delayed AIDS progression except in some specific cohorts including MACS cohorts (RH = 0.38, 95% Cl: 0.17-0.59 for time to AIDS; RH = 0.27, 95% Cl: 0.07-0.46 for time to death at the study entry.Overall, no significant association was found between SDF1 polymorphism and HIV susceptibility. A protective effect of SDF1 on AIDS progression and death was seen especially in two studies based on the same cohorts. In conclusion, SDF1 polymorphism exerts a moderate protective effect against AIDS disease

  12. Association of rs6265 and rs2030324 polymorphisms in brain-derived neurotrophic factor gene with Alzheimer's disease: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yan Lin

    Full Text Available BACKGROUND: The association between polymorphisms rs6265 and rs2030324 in brain-derived neurotrophic factor (BDNF and Alzheimer's disease (AD has been widely reported, but the results remain controversial. METHODS: A comprehensive search of Pubmed, Web of Science, China National Knowledge Infrastructure (CNKI, Wanfang Med Online and China Biology Medical literature database (CBM was performed. Pooled odds ratios (ORs with 95% confidence intervals (CIs were calculated using fixed or random-effects models. We excluded the studies with OR>3.0 or OR<0.3 for sensitive analysis. Subgroup analysis by ethnicity, form of AD and gender was carried out. Meta-regression was conducted to explore the potential sources of between-study heterogeneity. RESULTS: 29 articles with 7548 cases and 7334 controls concerning rs6265 and 22 articles with 5796 cases and 5706 controls concerning rs2030324 were included in this meta-analysis. The combined evidence suggested rs6265 contributing significantly to the increased risk of AD in females (codominant: fixed-effects model (FEM: OR = 1.13, 95% CI = 1.04-1.23; dominant: FEM: OR = 1.17, 95% CI = 1.05-1.31, especially for Caucasian females (codominant: FEM: OR = 1.18, 95% CI = 1.03-1.34; dominant: FEM: OR = 1.18, 95% CI = 1.01-1.37 and female late-onset Alzheimer's disease (LOAD patients (codominant: FEM: OR = 1.22, 95% CI = 1.05-1.41; dominant: FEM: OR = 1.23, 95% CI = 1.03-1.46. No evidence indicated an association between rs2030324 with AD in codominant (random-effects model (REM: OR = 1.06, 95% CI = 0.89-1.26 and dominant (REM: OR = 1.05, 95% CI = 0.86-1.27 models. CONCLUSION: This meta-analysis suggested A allele of rs6265 might increase the risk of AD in Caucasian females and female LOAD patients. In addition, no evidence indicated an association between rs2030324 with AD. Further studies are needed to confirm these results.

  13. Adaptive Evolution of Gene Expression in Drosophila

    Directory of Open Access Journals (Sweden)

    Armita Nourmohammad

    2017-08-01

    Full Text Available Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis.

  14. Allen Brain Atlas-Driven Visualizations: a web-based gene expression energy visualization tool.

    Science.gov (United States)

    Zaldivar, Andrew; Krichmar, Jeffrey L

    2014-01-01

    The Allen Brain Atlas-Driven Visualizations (ABADV) is a publicly accessible web-based tool created to retrieve and visualize expression energy data from the Allen Brain Atlas (ABA) across multiple genes and brain structures. Though the ABA offers their own search engine and software for researchers to view their growing collection of online public data sets, including extensive gene expression and neuroanatomical data from human and mouse brain, many of their tools limit the amount of genes and brain structures researchers can view at once. To complement their work, ABADV generates multiple pie charts, bar charts and heat maps of expression energy values for any given set of genes and brain structures. Such a suite of free and easy-to-understand visualizations allows for easy comparison of gene expression across multiple brain areas. In addition, each visualization links back to the ABA so researchers may view a summary of the experimental detail. ABADV is currently supported on modern web browsers and is compatible with expression energy data from the Allen Mouse Brain Atlas in situ hybridization data. By creating this web application, researchers can immediately obtain and survey numerous amounts of expression energy data from the ABA, which they can then use to supplement their work or perform meta-analysis. In the future, we hope to enable ABADV across multiple data resources.

  15. Allen Brain Atlas-Driven Visualizations: A Web-Based Gene Expression Energy Visualization Tool

    Directory of Open Access Journals (Sweden)

    Andrew eZaldivar

    2014-05-01

    Full Text Available The Allen Brain Atlas-Driven Visualizations (ABADV is a publicly accessible web-based tool created to retrieve and visualize expression energy data from the Allen Brain Atlas (ABA across multiple genes and brain structures. Though the ABA offers their own search engine and software for researchers to view their growing collection of online public data sets, including extensive gene expression and neuroanatomical data from human and mouse brain, many of their tools limit the amount of genes and brain structures researchers can view at once. To complement their work, ABADV generates multiple pie charts, bar charts and heat maps of expression energy values for any given set of genes and brain structures. Such a suite of free and easy-to-understand visualizations allows for easy comparison of gene expression across multiple brain areas. In addition, each visualization links back to the ABA so researchers may view a summary of the experimental detail. ABADV is currently supported on modern web browsers and is compatible with expression energy data from the Allen Mouse Brain Atlas in situ hybridization data. By creating this web application, researchers can immediately obtain and survey numerous amounts of expression energy data from the ABA, which they can then use to supplement their work or perform meta-analysis. In the future, we hope to enable ABADV across multiple data resources.

  16. Determining Physical Mechanisms of Gene Expression Regulation from Single Cell Gene Expression Data

    OpenAIRE

    Ezer, Daphne; Moignard, Victoria; G?ttgens, Berthold; Adryan, Boris

    2016-01-01

    Many genes are expressed in bursts, which can contribute to cell-to-cell heterogeneity. It is now possible to measure this heterogeneity with high throughput single cell gene expression assays (single cell qPCR and RNA-seq). These experimental approaches generate gene expression distributions which can be used to estimate the kinetic parameters of gene expression bursting, namely the rate that genes turn on, the rate that genes turn off, and the rate of transcription. We construct a complete ...

  17. The evolution of gene expression in primates

    OpenAIRE

    Tashakkori Ghanbarian, Avazeh

    2015-01-01

    The evolution of a gene’s expression profile is commonly assumed to be independent of its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between expression of neighboring genes in extant taxa. Indeed, in all eukaryotic genomes, genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their e...

  18. Integration of machine learning and meta-analysis identifies the transcriptomic bio-signature of mastitis disease in cattle.

    Science.gov (United States)

    Sharifi, Somayeh; Pakdel, Abbas; Ebrahimi, Mansour; Reecy, James M; Fazeli Farsani, Samaneh; Ebrahimie, Esmaeil

    2018-01-01

    Gram-negative bacteria such as Escherichia coli (E. coli) are assumed to be among the main agents that cause severe mastitis disease with clinical signs in dairy cattle. Rapid detection of this disease is so important in order to prevent transmission to other cows and helps to reduce inappropriate use of antibiotics. With the rapid progress in high-throughput technologies, and accumulation of various kinds of '-omics' data in public repositories, there is an opportunity to retrieve, integrate, and reanalyze these resources to improve the diagnosis and treatment of different diseases and to provide mechanistic insights into host resistance in an efficient way. Meta-analysis is a relatively inexpensive option with good potential to increase the statistical power and generalizability of single-study analysis. In the current meta-analysis research, six microarray-based studies that investigate the transcriptome profile of mammary gland tissue after induced mastitis by E. coli infection were used. This meta-analysis not only reinforced the findings in individual studies, but also several novel terms including responses to hypoxia, response to drug, anti-apoptosis and positive regulation of transcription from RNA polymerase II promoter enriched by up-regulated genes. Finally, in order to identify the small sets of genes that are sufficiently informative in E. coli mastitis, the differentially expressed gene introduced by meta-analysis were prioritized by using ten different attribute weighting algorithms. Twelve meta-genes were detected by the majority of attribute weighting algorithms (with weight above 0.7) as most informative genes including CXCL8 (IL8), NFKBIZ, HP, ZC3H12A, PDE4B, CASP4, CXCL2, CCL20, GRO1(CXCL1), CFB, S100A9, and S100A8. Interestingly, the results have been demonstrated that all of these genes are the key genes in the immune response, inflammation or mastitis. The Decision tree models efficiently discovered the best combination of the meta-genes as

  19. Meta-Analysis of Microarray Data of Rainbow Trout Fry Gonad Differentiation Modulated by Ethynylestradiol.

    Directory of Open Access Journals (Sweden)

    Sophie Depiereux

    Full Text Available Sex differentiation in fish is a highly labile process easily reversed by the use of exogenous hormonal treatment and has led to environmental concerns since low doses of estrogenic molecules can adversely impact fish reproduction. The goal of this study was to identify pathways altered by treatment with ethynylestradiol (EE2 in developing fish and to find new target genes to be tested further for their possible role in male-to-female sex transdifferentiation. To this end, we have successfully adapted a previously developed bioinformatics workflow to a meta-analysis of two datasets studying sex reversal following exposure to EE2 in juvenile rainbow trout. The meta-analysis consisted of retrieving the intersection of the top gene lists generated for both datasets, performed at different levels of stringency. The intersecting gene lists, enriched in true positive differentially expressed genes (DEGs, were subjected to over-representation analysis (ORA which allowed identifying several statistically significant enriched pathways altered by EE2 treatment and several new candidate pathways, such as progesterone-mediated oocyte maturation and PPAR signalling. Moreover, several relevant key genes potentially implicated in the early transdifferentiation process were selected. Altogether, the results show that EE2 has a great effect on gene expression in juvenile rainbow trout. The feminization process seems to result from the altered transcription of genes implicated in normal female gonad differentiation, resulting in expression similar to that observed in normal females (i.e. the repression of key testicular markers cyp17a1, cyp11b, tbx1, as well as from other genes (including transcription factors that respond specifically to the EE2 treatment. The results also showed that the bioinformatics workflow can be applied to different types of microarray platforms and could be generalized to (ecotoxicogenomics studies for environmental risk assessment

  20. Meta-analysis of CDKN2A methylation to find its role in prostate cancer development and progression, and also to find the effect of CDKN2A expression on disease-free survival (PRISMA).

    Science.gov (United States)

    Cao, Zipei; Wei, Lijuan; Zhu, Weizhi; Yao, Xuping

    2018-03-01

    Reduction of cyclin-dependent kinase inhibitor 2A (CDKN2A) (p16 and p14) expression through DNA methylation has been reported in prostate cancer (PCa). This meta-analysis was conducted to assess the difference of p16 and p14 methylation between PCa and different histological types of nonmalignant controls and the correlation of p16 or p14 methylation with clinicopathological features of PCa. According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, articles were searched in PubMed, Embase, EBSCO, Wanfang, and CNKI databases. The strength of correlation was calculated by the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Trial sequential analysis (TSA) was used to estimate the required population information for significant results. A total of 20 studies published from 1997 to 2017 were identified in this meta-analysis, including 1140 PCa patients and 530 cases without cancer. Only p16 methylation in PCa was significantly higher than in benign prostatic lesions (OR = 4.72, P = .011), but had a similar level in PCa and adjacent tissues or high-grade prostatic intraepithelial neoplasias (HGPIN). TSA revealed that this analysis on p16 methylation is a false positive result in cancer versus benign prostatic lesions (the estimated required information size of 5116 participants). p16 methylation was not correlated with PCa in the urine and blood. Besides, p16 methylation was not linked to clinical stage, prostate-specific antigen (PSA) level, and Gleason score (GS) of patients with PCa. p14 methylation was not correlated with PCa in tissue and urine samples. No correlation was observed between p14 methylation and clinical stage or GS. CDKN2A mutation and copy number alteration were not associated with prognosis of PCa in overall survival and disease-free survival. CDKN2A expression was not correlated with the prognosis of PCa in overall survival (492 cases) (P > .1

  1. Association between H3K4 methylation and cancer prognosis: A meta-analysis.

    Science.gov (United States)

    Li, Simin; Shen, Luyan; Chen, Ke-Neng

    2018-05-08

    Histone H3 lysine 4 methylation (H3K4 methylation), including mono-methylation (H3K4me1), di-methylation (H3K4me2), or tri-methylation (H3K4me3), is one of the epigenetic modifications to histone proteins, which are related to the transcriptional activation of genes. H3K4 methylation has both tumor inhibiting and promoting effects, and the prognostic value of H3K4 methylation in cancer remains controversial. Therefore, we performed a systematic review and meta-analysis to examine the association between H3K4 methylation and cancer prognosis. A comprehensive search of PubMed, Web of Science, ScienceDirect, Embase, and Ovid databases was conducted to identify studies investigating the association between H3K4 methylation and prognosis of patients with malignant tumors. The data and characteristics of each study were extracted, and the hazard ratio (HR) at a 95% confidence interval (CI) was calculated to estimate the effect. A total of 1474 patients in 10 studies were enrolled in this meta-analysis. The pooled HR of 1.52 (95% CI 1.02-2.26) indicated that patients with a lower level of H3K4me2 expression were expected to have shorter overall survival, while the pooled HR of 0.45 (95% CI 0.27-0.74) indicated that patients with a lower level of H3K4me3 expression were expected to have longer overall survival. This meta-analysis indicates that increased H3K4me3 expression and decreased H3K4me2 expression might be predictive factors of poor prognosis in cancer. Further large cohort studies are needed to confirm these findings. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  2. Methods for monitoring multiple gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Berka, Randy [Davis, CA; Bachkirova, Elena [Davis, CA; Rey, Michael [Davis, CA

    2012-05-01

    The present invention relates to methods for monitoring differential expression of a plurality of genes in a first filamentous fungal cell relative to expression of the same genes in one or more second filamentous fungal cells using microarrays containing Trichoderma reesei ESTs or SSH clones, or a combination thereof. The present invention also relates to computer readable media and substrates containing such array features for monitoring expression of a plurality of genes in filamentous fungal cells.

  3. Methods for monitoring multiple gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Berka, Randy; Bachkirova, Elena; Rey, Michael

    2013-10-01

    The present invention relates to methods for monitoring differential expression of a plurality of genes in a first filamentous fungal cell relative to expression of the same genes in one or more second filamentous fungal cells using microarrays containing Trichoderma reesei ESTs or SSH clones, or a combination thereof. The present invention also relates to computer readable media and substrates containing such array features for monitoring expression of a plurality of genes in filamentous fungal cells.

  4. cis sequence effects on gene expression

    Directory of Open Access Journals (Sweden)

    Jacobs Kevin

    2007-08-01

    Full Text Available Abstract Background Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. Results We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p cis sequence effects in our study, respectively. Conclusion Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.

  5. Gene expression inference with deep learning.

    Science.gov (United States)

    Chen, Yifei; Li, Yi; Narayan, Rajiv; Subramanian, Aravind; Xie, Xiaohui

    2016-06-15

    Large-scale gene expression profiling has been widely used to characterize cellular states in response to various disease conditions, genetic perturbations, etc. Although the cost of whole-genome expression profiles has been dropping steadily, generating a compendium of expression profiling over thousands of samples is still very expensive. Recognizing that gene expressions are often highly correlated, researchers from the NIH LINCS program have developed a cost-effective strategy of profiling only ∼1000 carefully selected landmark genes and relying on computational methods to infer the expression of remaining target genes. However, the computational approach adopted by the LINCS program is currently based on linear regression (LR), limiting its accuracy since it does not capture complex nonlinear relationship between expressions of genes. We present a deep learning method (abbreviated as D-GEX) to infer the expression of target genes from the expression of landmark genes. We used the microarray-based Gene Expression Omnibus dataset, consisting of 111K expression profiles, to train our model and compare its performance to those from other methods. In terms of mean absolute error averaged across all genes, deep learning significantly outperforms LR with 15.33% relative improvement. A gene-wise comparative analysis shows that deep learning achieves lower error than LR in 99.97% of the target genes. We also tested the performance of our learned model on an independent RNA-Seq-based GTEx dataset, which consists of 2921 expression profiles. Deep learning still outperforms LR with 6.57% relative improvement, and achieves lower error in 81.31% of the target genes. D-GEX is available at https://github.com/uci-cbcl/D-GEX CONTACT: xhx@ics.uci.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Identification of a set of genes showing regionally enriched expression in the mouse brain

    Directory of Open Access Journals (Sweden)

    Marra Marco A

    2008-07-01

    Full Text Available Abstract Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters ( Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

  7. Determinants of human adipose tissue gene expression

    DEFF Research Database (Denmark)

    Viguerie, Nathalie; Montastier, Emilie; Maoret, Jean-José

    2012-01-01

    weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong...... interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index...... on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently...

  8. Deriving Trading Rules Using Gene Expression Programming

    Directory of Open Access Journals (Sweden)

    Adrian VISOIU

    2011-01-01

    Full Text Available This paper presents how buy and sell trading rules are generated using gene expression programming with special setup. Market concepts are presented and market analysis is discussed with emphasis on technical analysis and quantitative methods. The use of genetic algorithms in deriving trading rules is presented. Gene expression programming is applied in a form where multiple types of operators and operands are used. This gives birth to multiple gene contexts and references between genes in order to keep the linear structure of the gene expression programming chromosome. The setup of multiple gene contexts is presented. The case study shows how to use the proposed gene setup to derive trading rules encoded by Boolean expressions, using a dataset with the reference exchange rates between the Euro and the Romanian leu. The conclusions highlight the positive results obtained in deriving useful trading rules.

  9. Polycistronic gene expression in Aspergillus niger.

    Science.gov (United States)

    Schuetze, Tabea; Meyer, Vera

    2017-09-25

    Genome mining approaches predict dozens of biosynthetic gene clusters in each of the filamentous fungal genomes sequenced so far. However, the majority of these gene clusters still remain cryptic because they are not expressed in their natural host. Simultaneous expression of all genes belonging to a biosynthetic pathway in a heterologous host is one approach to activate biosynthetic gene clusters and to screen the metabolites produced for bioactivities. Polycistronic expression of all pathway genes under control of a single and tunable promoter would be the method of choice, as this does not only simplify cloning procedures, but also offers control on timing and strength of expression. However, polycistronic gene expression is a feature not commonly found in eukaryotic host systems, such as Aspergillus niger. In this study, we tested the suitability of the viral P2A peptide for co-expression of three genes in A. niger. Two genes descend from Fusarium oxysporum and are essential to produce the secondary metabolite enniatin (esyn1, ekivR). The third gene (luc) encodes the reporter luciferase which was included to study position effects. Expression of the polycistronic gene cassette was put under control of the Tet-On system to ensure tunable gene expression in A. niger. In total, three polycistronic expression cassettes which differed in the position of luc were constructed and targeted to the pyrG locus in A. niger. This allowed direct comparison of the luciferase activity based on the position of the luciferase gene. Doxycycline-mediated induction of the Tet-On expression cassettes resulted in the production of one long polycistronic mRNA as proven by Northern analyses, and ensured comparable production of enniatin in all three strains. Notably, gene position within the polycistronic expression cassette matters, as, luciferase activity was lowest at position one and had a comparable activity at positions two and three. The P2A peptide can be used to express at

  10. Profiling Gene Expression in Germinating Brassica Roots.

    Science.gov (United States)

    Park, Myoung Ryoul; Wang, Yi-Hong; Hasenstein, Karl H

    2014-01-01

    Based on previously developed solid-phase gene extraction (SPGE) we examined the mRNA profile in primary roots of Brassica rapa seedlings for highly expressed genes like ACT7 (actin7), TUB (tubulin1), UBQ (ubiquitin), and low expressed GLK (glucokinase) during the first day post-germination. The assessment was based on the mRNA load of the SPGE probe of about 2.1 ng. The number of copies of the investigated genes changed spatially along the length of primary roots. The expression level of all genes differed significantly at each sample position. Among the examined genes ACT7 expression was most even along the root. UBQ was highest at the tip and root-shoot junction (RS). TUB and GLK showed a basipetal gradient. The temporal expression of UBQ was highest in the MZ 9 h after primary root emergence and higher than at any other sample position. Expressions of GLK in EZ and RS increased gradually over time. SPGE extraction is the result of oligo-dT and oligo-dA hybridization and the results illustrate that SPGE can be used for gene expression profiling at high spatial and temporal resolution. SPGE needles can be used within two weeks when stored at 4 °C. Our data indicate that gene expression studies that are based on the entire root miss important differences in gene expression that SPGE is able to resolve for example growth adjustments during gravitropism.

  11. Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling.

    Directory of Open Access Journals (Sweden)

    Stéphanie Cornen

    Full Text Available Breast cancers (BCs of the luminal B subtype are estrogen receptor-positive (ER+, highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs, DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15 and UTRN (6q24, were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype.

  12. Association of interferon regulatory factor 4 gene polymorphisms rs12203592 and rs872071 with skin cancer and haematological malignancies susceptibility: a meta-analysis of 19 case–control studies

    International Nuclear Information System (INIS)

    Wang, Songtao; Yan, Qing; Chen, Pin; Zhao, Peng; Gu, Aihua

    2014-01-01

    Research has indicated that the rs12203592 and rs872071 interferon regulatory factor 4 (IRF4) gene polymorphisms correlate with the risk of cancer, especially skin cancer and haematological malignancies, but the results remain controversial. To understand better the effects of these two polymorphisms on skin cancer and haematological malignancies susceptibility, a cumulative meta-analysis was performed. We conducted a search using the PubMed and Web of Science databases for relevant case-control studies published before April 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using fixed- or random-effects models where appropriate. Heterogeneity test, publication bias test, and sensitivity analysis were also performed. In total, 11 articles comprised of 19 case–control studies were identified; five focused on the rs12203592 polymorphism with 7,992 cases and 8,849 controls, and six were on the rs872071 polymorphism with 3108 cases and 8300 controls. As for rs12203592, a significant correlation with overall skin cancer and haematological malignancies risk was found with the homozygote comparison model (OR = 1.566, 95% CI 1.087-2.256) and recessive model (OR = 1.526, 95% CI 1.107-2.104). For rs872071, a significantly elevated haematological malignancies risk was observed in all genetic models (homozygote comparison: OR = 1.805, 95% CI 1.402-2.323; heterozygote comparison: OR = 1.427, 95% CI 1.203-1.692; dominant: OR = 1.556, 95% CI 1.281-1.891; recessive: OR = 1.432, 95% CI 1.293-1.587; additive: OR = 1.349, 95% CI 1.201-1.515). Similarly, increased skin cancer and haematological malignancies risk was also identified after stratification of the SNP data by cancer type, ethnicity and source of controls for both polymorphisms. Our meta-analysis indicated that the rs12203592 and rs872071 IRF4 gene polymorphisms are associated with individual susceptibility to skin cancer and haematological malignancies. Moreover, the effect

  13. Chromatin loops, gene positioning, and gene expression

    NARCIS (Netherlands)

    Holwerda, S.; de Laat, W.

    2012-01-01

    Technological developments and intense research over the last years have led to a better understanding of the 3D structure of the genome and its influence on genome function inside the cell nucleus. We will summarize topological studies performed on four model gene loci: the alpha- and beta-globin

  14. Meta-analysis in microbiology

    Directory of Open Access Journals (Sweden)

    N Pabalan

    2014-01-01

    Full Text Available The use of meta-analysis in microbiology may facilitate decision-making that impacts public health policy. Directed at clinicians and researchers in microbiology, this review outlines the steps in performing this statistical technique, addresses its biases and describes its value in this discipline. The survey to estimate extent of the use of meta-analyses in microbiology shows the remarkable growth in the use of this research methodology, from a minimal Asian output to a level comparable with those of Europe and North America in the last 7 years.

  15. Serial analysis of gene expression (SAGE)

    NARCIS (Netherlands)

    van Ruissen, Fred; Baas, Frank

    2007-01-01

    In 1995, serial analysis of gene expression (SAGE) was developed as a versatile tool for gene expression studies. SAGE technology does not require pre-existing knowledge of the genome that is being examined and therefore SAGE can be applied to many different model systems. In this chapter, the SAGE

  16. Identification of Important Physiological Traits and Moderators That Are Associated with Improved Salt Tolerance in CBL and CIPK Overexpressors through a Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yuanchun Ma

    2017-05-01

    Full Text Available The CBL-CIPK pathway is a plant-specific Ca2+ sensor relaying pathway that has been shown to be involved in plant response to salt stress. Over-expression of CBL-CIPK network genes has been reported to increase salt tolerance in many studies. The studies on the overexpression of CBL-CIPK network genes, however, have used various indices to evaluate the effect of these genes on salt tolerance and have indicated a variety of roles for the major CBL-CIPK pathway genes. Therefore, it is of great interest to analyze the various effects resulting from the overexpression CBL-CIPK pathway genes and their relation to salt tolerance. The meta-analysis conducted in the present study investigated how over-expression of CBLs or CIPKs in transgenic plants affects the response to salt stress and identified the increase or decrease that occurs in these experimental variables when foreign CIPK or CBL genes are overexpressed in transgenic plants. The data from the collective studies on over-expression of CIPKs indicated that 6 of the 11 examined parameters (main effects increased by 22% or more, while two of the six examined parameters increased by at least 78% in transgenic plants overexpressing CBL genes. In addition to analyzing the impact of overexpression on the main effects, eight different modifying parameters were also analyzed. Results indicated that several moderators impact the extent to which overexpression of CBLs and CIPKs affect the main parameters. The majority of CBLs have been obtained from dicotyledonous plants and most of the CBLs and CIPKs have been expressed in dicotyledonous plants. In comparison to homologous expression, the meta-analysis indicated that heterogeneous expression of CBLs resulted in greater increases in seed germination. The results of the meta-analysis provide information that could be useful in designing research to examine the mechanisms by which CBL-CIPK pathway genes increase salt tolerance in plants.

  17. GTI: a novel algorithm for identifying outlier gene expression profiles from integrated microarray datasets.

    Directory of Open Access Journals (Sweden)

    John Patrick Mpindi

    Full Text Available BACKGROUND: Meta-analysis of gene expression microarray datasets presents significant challenges for statistical analysis. We developed and validated a new bioinformatic method for the identification of genes upregulated in subsets of samples of a given tumour type ('outlier genes', a hallmark of potential oncogenes. METHODOLOGY: A new statistical method (the gene tissue index, GTI was developed by modifying and adapting algorithms originally developed for statistical problems in economics. We compared the potential of the GTI to detect outlier genes in meta-datasets with four previously defined statistical methods, COPA, the OS statistic, the t-test and ORT, using simulated data. We demonstrated that the GTI performed equally well to existing methods in a single study simulation. Next, we evaluated the performance of the GTI in the analysis of combined Affymetrix gene expression data from several published studies covering 392 normal samples of tissue from the central nervous system, 74 astrocytomas, and 353 glioblastomas. According to the results, the GTI was better able than most of the previous methods to identify known oncogenic outlier genes. In addition, the GTI identified 29 novel outlier genes in glioblastomas, including TYMS and CDKN2A. The over-expression of these genes was validated in vivo by immunohistochemical staining data from clinical glioblastoma samples. Immunohistochemical data were available for 65% (19 of 29 of these genes, and 17 of these 19 genes (90% showed a typical outlier staining pattern. Furthermore, raltitrexed, a specific inhibitor of TYMS used in the therapy of tumour types other than glioblastoma, also effectively blocked cell proliferation in glioblastoma cell lines, thus highlighting this outlier gene candidate as a potential therapeutic target. CONCLUSIONS/SIGNIFICANCE: Taken together, these results support the GTI as a novel approach to identify potential oncogene outliers and drug targets. The algorithm is

  18. Expression of Sox genes in tooth development.

    Science.gov (United States)

    Kawasaki, Katsushige; Kawasaki, Maiko; Watanabe, Momoko; Idrus, Erik; Nagai, Takahiro; Oommen, Shelly; Maeda, Takeyasu; Hagiwara, Nobuko; Que, Jianwen; Sharpe, Paul T; Ohazama, Atsushi

    2015-01-01

    Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium. Sox13 showed restricted expression in the primary enamel knots. At the early bell stage, three Sox genes (Sox8, 11, 17 and 21) were expressed in pre-ameloblasts, whereas two others (Sox5 and 18) showed expression in odontoblasts. Sox genes thus showed a dynamic spatio-temporal expression during tooth development.

  19. Complex nature of SNP genotype effects on gene expression in primary human leucocytes

    Directory of Open Access Journals (Sweden)

    Dinesen Lotte C

    2009-01-01

    Full Text Available Abstract Background Genome wide association studies have been hugely successful in identifying disease risk variants, yet most variants do not lead to coding changes and how variants influence biological function is usually unknown. Methods We correlated gene expression and genetic variation in untouched primary leucocytes (n = 110 from individuals with celiac disease – a common condition with multiple risk variants identified. We compared our observations with an EBV-transformed HapMap B cell line dataset (n = 90, and performed a meta-analysis to increase power to detect non-tissue specific effects. Results In celiac peripheral blood, 2,315 SNP variants influenced gene expression at 765 different transcripts (cis expression quantitative trait loci, eQTLs. 135 of the detected SNP-probe effects (reflecting 51 unique probes were also detected in a HapMap B cell line published dataset, all with effects in the same allelic direction. Overall gene expression differences within the two datasets predominantly explain the limited overlap in observed cis-eQTLs. Celiac associated risk variants from two regions, containing genes IL18RAP and CCR3, showed significant cis genotype-expression correlations in the peripheral blood but not in the B cell line datasets. We identified 14 genes where a SNP affected the expression of different probes within the same gene, but in opposite allelic directions. By incorporating genetic variation in co-expression analyses, functional relationships between genes can be more significantly detected. Conclusion In conclusion, the complex nature of genotypic effects in human populations makes the use of a relevant tissue, large datasets, and analysis of different exons essential to enable the identification of the function for many genetic risk variants in common diseases.

  20. Positron emission tomography imaging of gene expression

    International Nuclear Information System (INIS)

    Tang Ganghua

    2001-01-01

    The merging of molecular biology and nuclear medicine is developed into molecular nuclear medicine. Positron emission tomography (PET) of gene expression in molecular nuclear medicine has become an attractive area. Positron emission tomography imaging gene expression includes the antisense PET imaging and the reporter gene PET imaging. It is likely that the antisense PET imaging will lag behind the reporter gene PET imaging because of the numerous issues that have not yet to be resolved with this approach. The reporter gene PET imaging has wide application into animal experimental research and human applications of this approach will likely be reported soon

  1. The functional landscape of mouse gene expression

    Directory of Open Access Journals (Sweden)

    Zhang Wen

    2004-12-01

    Full Text Available Abstract Background Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. Results We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. Conclusions We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.

  2. OHBM 2017: Practical intensity based meta-analysis

    OpenAIRE

    Maumet, Camille

    2017-01-01

    "Practical intensity-based meta-analysis" slides from my talk in the OHBM 2017 educational talk on Neuroimaging meta-analysis.http://www.humanbrainmapping.org/files/2017/ED Courses/Neuroimaging Meta-Analysis.pdf

  3. A comparative gene expression database for invertebrates

    Directory of Open Access Journals (Sweden)

    Ormestad Mattias

    2011-08-01

    Full Text Available Abstract Background As whole genome and transcriptome sequencing gets cheaper and faster, a great number of 'exotic' animal models are emerging, rapidly adding valuable data to the ever-expanding Evo-Devo field. All these new organisms serve as a fantastic resource for the research community, but the sheer amount of data, some published, some not, makes detailed comparison of gene expression patterns very difficult to summarize - a problem sometimes even noticeable within a single lab. The need to merge existing data with new information in an organized manner that is publicly available to the research community is now more necessary than ever. Description In order to offer a homogenous way of storing and handling gene expression patterns from a variety of organisms, we have developed the first web-based comparative gene expression database for invertebrates that allows species-specific as well as cross-species gene expression comparisons. The database can be queried by gene name, developmental stage and/or expression domains. Conclusions This database provides a unique tool for the Evo-Devo research community that allows the retrieval, analysis and comparison of gene expression patterns within or among species. In addition, this database enables a quick identification of putative syn-expression groups that can be used to initiate, among other things, gene regulatory network (GRN projects.

  4. Adaptive Evolution of Gene Expression in Drosophila.

    Science.gov (United States)

    Nourmohammad, Armita; Rambeau, Joachim; Held, Torsten; Kovacova, Viera; Berg, Johannes; Lässig, Michael

    2017-08-08

    Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Differential gene expression during Trypanosoma cruzi metacyclogenesis

    Directory of Open Access Journals (Sweden)

    Marco Aurelio Krieger

    1999-09-01

    Full Text Available The transformation of epimastigotes into metacyclic trypomastigotes involves changes in the pattern of expressed genes, resulting in important morphological and functional differences between these developmental forms of Trypanosoma cruzi. In order to identify and characterize genes involved in triggering the metacyclogenesis process and in conferring to metacyclic trypomastigotes their stage specific biological properties, we have developed a method allowing the isolation of genes specifically expressed when comparing two close related cell populations (representation of differential expression or RDE. The method is based on the PCR amplification of gene sequences selected by hybridizing and subtracting the populations in such a way that after some cycles of hybridization-amplification genes specific to a given population are highly enriched. The use of this method in the analysis of differential gene expression during T. cruzi metacyclogenesis (6 hr and 24 hr of differentiation and metacyclic trypomastigotes resulted in the isolation of several clones from each time point. Northern blot analysis showed that some genes are transiently expressed (6 hr and 24 hr differentiating cells, while others are present in differentiating cells and in metacyclic trypomastigotes. Nucleotide sequencing of six clones characterized so far showed that they do not display any homology to gene sequences available in the GeneBank.

  6. Meta-Analysis in Stata Using Gllamm

    Science.gov (United States)

    Bagos, Pantelis G.

    2015-01-01

    There are several user-written programs for performing meta-analysis in Stata (Stata Statistical Software: College Station, TX: Stata Corp LP). These include metan, metareg, mvmeta, and glst. However, there are several cases for which these programs do not suffice. For instance, there is no software for performing univariate meta-analysis with…

  7. Trial Sequential Methods for Meta-Analysis

    Science.gov (United States)

    Kulinskaya, Elena; Wood, John

    2014-01-01

    Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

  8. Statistical Power in Meta-Analysis

    Science.gov (United States)

    Liu, Jin

    2015-01-01

    Statistical power is important in a meta-analysis study, although few studies have examined the performance of simulated power in meta-analysis. The purpose of this study is to inform researchers about statistical power estimation on two sample mean difference test under different situations: (1) the discrepancy between the analytical power and…

  9. Bayesian Meta-Analysis of Coefficient Alpha

    Science.gov (United States)

    Brannick, Michael T.; Zhang, Nanhua

    2013-01-01

    The current paper describes and illustrates a Bayesian approach to the meta-analysis of coefficient alpha. Alpha is the most commonly used estimate of the reliability or consistency (freedom from measurement error) for educational and psychological measures. The conventional approach to meta-analysis uses inverse variance weights to combine…

  10. Online open neuroimaging mass meta-analysis

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup; Kempton, Matthew J.; Williams, Steven C. R.

    We describe a system for meta-analysis where a wiki stores numerical data in a simple format and a web service performs the numerical computation. We initially apply the system on multiple meta-analyses of structural neuroimaging data results. The described system allows for mass meta-analysis, e...

  11. Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals

    NARCIS (Netherlands)

    Bouwman, Aniek C.; Daetwyler, Hans D.; Chamberlain, Amanda J.; Ponce, Carla Hurtado; Sargolzaei, Mehdi; Schenkel, Flavio S.; Sahana, Goutam; Govignon-Gion, Armelle; Boitard, Simon; Dolezal, Marlies; Pausch, Hubert; Brøndum, Rasmus F.; Bowman, Phil J.; Thomsen, Bo; Guldbrandtsen, Bernt; Lund, Mogens S.; Servin, Bertrand; Garrick, Dorian J.; Reecy, James; Vilkki, Johanna; Bagnato, Alessandro; Wang, Min; Hoff, Jesse L.; Schnabel, Robert D.; Taylor, Jeremy F.; Vinkhuyzen, Anna A.E.; Panitz, Frank; Bendixen, Christian; Holm, Lars Erik; Gredler, Birgit; Hozé, Chris; Boussaha, Mekki; Sanchez, Marie Pierre; Rocha, Dominique; Capitan, Aurelien; Tribout, Thierry; Barbat, Anne; Croiseau, Pascal; Drögemüller, Cord; Jagannathan, Vidhya; Vander Jagt, Christy; Crowley, John J.; Bieber, Anna; Purfield, Deirdre C.; Berry, Donagh P.; Emmerling, Reiner; Götz, Kay Uwe; Frischknecht, Mirjam; Russ, Ingolf; Sölkner, Johann; Tassell, van Curtis P.; Fries, Ruedi; Stothard, Paul; Veerkamp, Roel F.; Boichard, Didier; Goddard, Mike E.; Hayes, Ben J.

    2018-01-01

    Stature is affected by many polymorphisms of small effect in humans1. In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and

  12. T64A polymorphism in beta3-adrenergic receptor gene (ADRB3) and coronary heart disease: a case-cohort study and meta-analysis

    NARCIS (Netherlands)

    Zafarmand, M. H.; van der Schouw, Y. T.; Grobbee, D. E.; de Leeuw, P. W.; Bots, M. L.

    2008-01-01

    A missense mutation of the human ADRB3 gene replacing tryptophan with arginine at codon 64 (Trp64Arg) has been related to obesity, insulin resistance, earlier onset of noninsulin-dependent diabetes mellitus and hypertension. These findings may also suggest an increased risk of coronary heart disease

  13. The M235T polymorphism in the AGT gene and CHD risk: evidence of a Hardy-Weinberg equilibrium violation and publication bias in a meta-analysis

    NARCIS (Netherlands)

    Zafarmand, Mohammad Hadi; van der Schouw, Yvonne T.; Grobbee, Diederick E.; de Leeuw, Peter W.; Bots, Michiel L.

    2008-01-01

    The M235T polymorphism in the AGT gene has been related to an increased risk of hypertension. This finding may also suggest an increased risk of coronary heart disease (CHD). A case-cohort study was conducted in 1,732 unrelated middle-age women (210 CHD cases and 1,522 controls) from a prospective

  14. Stochastic gene expression in Arabidopsis thaliana.

    Science.gov (United States)

    Araújo, Ilka Schultheiß; Pietsch, Jessica Magdalena; Keizer, Emma Mathilde; Greese, Bettina; Balkunde, Rachappa; Fleck, Christian; Hülskamp, Martin

    2017-12-14

    Although plant development is highly reproducible, some stochasticity exists. This developmental stochasticity may be caused by noisy gene expression. Here we analyze the fluctuation of protein expression in Arabidopsis thaliana. Using the photoconvertible KikGR marker, we show that the protein expressions of individual cells fluctuate over time. A dual reporter system was used to study extrinsic and intrinsic noise of marker gene expression. We report that extrinsic noise is higher than intrinsic noise and that extrinsic noise in stomata is clearly lower in comparison to several other tissues/cell types. Finally, we show that cells are coupled with respect to stochastic protein expression in young leaves, hypocotyls and roots but not in mature leaves. Our data indicate that stochasticity of gene expression can vary between tissues/cell types and that it can be coupled in a non-cell-autonomous manner.

  15. A Case-Control Study and Meta-Analysis Reveal BDNF Val66Met Is a Possible Risk Factor for PTSD

    Directory of Open Access Journals (Sweden)

    Dagmar Bruenig

    2016-01-01

    Full Text Available Posttraumatic stress disorder (PTSD is a debilitating condition that develops in some people after exposure to a traumatic event. Brain-derived neurotrophic factor (BDNF is highly expressed in the mammalian brain and is thought to be involved in learning and memory processes. A nonsynonymous polymorphism in the BDNF gene, rs6265 (Val66Met, has been hypothesised to be associated with PTSD. Association studies examining the Val66Met polymorphism and PTSD have been inconclusive, likely due to the variability in type of trauma exposure analysed. Vietnam veterans (n=257 screened for PTSD and controlled for trauma exposure were genotyped for BDNF Val66Met. The association was not significant so we incorporated our data into a meta-analysis to obtain greater statistical power. A comprehensive search of more than 1237 articles revealed eight additional studies suitable for meta-analysis (n=3625. A random-effects meta-analysis observed a potential protective factor of the Val/Val genotype. After removing two studies with violation of Hardy-Weinberg equilibrium, findings for the Val/Val genotype reached significance. Subgroup analyses confirmed a trend for this finding. Limitations of some studies that inform this meta-analysis include poorly screened controls and a lack of examination of population stratification. Effectively designed studies should inform this line of research in the future.

  16. Gene expression in periodontal tissues following treatment

    Directory of Open Access Journals (Sweden)

    Eisenacher Martin

    2008-07-01

    Full Text Available Abstract Background In periodontitis, treatment aimed at controlling the periodontal biofilm infection results in a resolution of the clinical and histological signs of inflammation. Although the cell types found in periodontal tissues following treatment have been well described, information on gene expression is limited to few candidate genes. Therefore, the aim of the study was to determine the expression profiles of immune and inflammatory genes in periodontal tissues from sites with severe chronic periodontitis following periodontal therapy in order to identify genes involved in tissue homeostasis. Gingival biopsies from 12 patients with severe chronic periodontitis were taken six to eight weeks following non-surgical periodontal therapy, and from 11 healthy controls. As internal standard, RNA of an immortalized human keratinocyte line (HaCaT was used. Total RNA was subjected to gene expression profiling using a commercially available microarray system focusing on inflammation-related genes. Post-hoc confirmation of selected genes was done by Realtime-PCR. Results Out of the 136 genes analyzed, the 5% most strongly expressed genes compared to healthy controls were Interleukin-12A (IL-12A, Versican (CSPG-2, Matrixmetalloproteinase-1 (MMP-1, Down syndrome critical region protein-1 (DSCR-1, Macrophage inflammatory protein-2β (Cxcl-3, Inhibitor of apoptosis protein-1 (BIRC-1, Cluster of differentiation antigen 38 (CD38, Regulator of G-protein signalling-1 (RGS-1, and Finkel-Biskis-Jinkins murine osteosarcoma virus oncogene (C-FOS; the 5% least strongly expressed genes were Receptor-interacting Serine/Threonine Kinase-2 (RIP-2, Complement component 3 (C3, Prostaglandin-endoperoxide synthase-2 (COX-2, Interleukin-8 (IL-8, Endothelin-1 (EDN-1, Plasminogen activator inhibitor type-2 (PAI-2, Matrix-metalloproteinase-14 (MMP-14, and Interferon regulating factor-7 (IRF-7. Conclusion Gene expression profiles found in periodontal tissues following

  17. Widespread ectopic expression of olfactory receptor genes

    Directory of Open Access Journals (Sweden)

    Yanai Itai

    2006-05-01

    Full Text Available Abstract Background Olfactory receptors (ORs are the largest gene family in the human genome. Although they are expected to be expressed specifically in olfactory tissues, some ectopic expression has been reported, with special emphasis on sperm and testis. The present study systematically explores the expression patterns of OR genes in a large number of tissues and assesses the potential functional implication of such ectopic expression. Results We analyzed the expression of hundreds of human and mouse OR transcripts, via EST and microarray data, in several dozens of human and mouse tissues. Different tissues had specific, relatively small OR gene subsets which had particularly high expression levels. In testis, average expression was not particularly high, and very few highly expressed genes were found, none corresponding to ORs previously implicated in sperm chemotaxis. Higher expression levels were more common for genes with a non-OR genomic neighbor. Importantly, no correlation in expression levels was detected for human-mouse orthologous pairs. Also, no significant difference in expression levels was seen between intact and pseudogenized ORs, except for the pseudogenes of subfamily 7E which has undergone a human-specific expansion. Conclusion The OR superfamily as a whole, show widespread, locus-dependent and heterogeneous expression, in agreement with a neutral or near neutral evolutionary model for transcription control. These results cannot reject the possibility that small OR subsets might play functional roles in different tissues, however considerable care should be exerted when offering a functional interpretation for ectopic OR expression based only on transcription information.

  18. Regulation of Gene Expression in Protozoa Parasites

    Directory of Open Access Journals (Sweden)

    Consuelo Gomez

    2010-01-01

    Full Text Available Infections with protozoa parasites are associated with high burdens of morbidity and mortality across the developing world. Despite extensive efforts to control the transmission of these parasites, the spread of populations resistant to drugs and the lack of effective vaccines against them contribute to their persistence as major public health problems. Parasites should perform a strict control on the expression of genes involved in their pathogenicity, differentiation, immune evasion, or drug resistance, and the comprehension of the mechanisms implicated in that control could help to develop novel therapeutic strategies. However, until now these mechanisms are poorly understood in protozoa. Recent investigations into gene expression in protozoa parasites suggest that they possess many of the canonical machineries employed by higher eukaryotes for the control of gene expression at transcriptional, posttranscriptional, and epigenetic levels, but they also contain exclusive mechanisms. Here, we review the current understanding about the regulation of gene expression in Plasmodium sp., Trypanosomatids, Entamoeba histolytica and Trichomonas vaginalis.

  19. Regulation of gene expression in protozoa parasites.

    Science.gov (United States)

    Gomez, Consuelo; Esther Ramirez, M; Calixto-Galvez, Mercedes; Medel, Olivia; Rodríguez, Mario A

    2010-01-01

    Infections with protozoa parasites are associated with high burdens of morbidity and mortality across the developing world. Despite extensive efforts to control the transmission of these parasites, the spread of populations resistant to drugs and the lack of effective vaccines against them contribute to their persistence as major public health problems. Parasites should perform a strict control on the expression of genes involved in their pathogenicity, differentiation, immune evasion, or drug resistance, and the comprehension of the mechanisms implicated in that control could help to develop novel therapeutic strategies. However, until now these mechanisms are poorly understood in protozoa. Recent investigations into gene expression in protozoa parasites suggest that they possess many of the canonical machineries employed by higher eukaryotes for the control of gene expression at transcriptional, posttranscriptional, and epigenetic levels, but they also contain exclusive mechanisms. Here, we review the current understanding about the regulation of gene expression in Plasmodium sp., Trypanosomatids, Entamoeba histolytica and Trichomonas vaginalis.

  20. Inferring gene networks from discrete expression data

    KAUST Repository

    Zhang, L.; Mallick, B. K.

    2013-01-01

    graphical models applied to continuous data, which give a closedformmarginal likelihood. In this paper,we extend network modeling to discrete data, specifically data from serial analysis of gene expression, and RNA-sequencing experiments, both of which

  1. Gene Expression and Microarray Investigation of Dendrobium ...

    African Journals Online (AJOL)

    blood glucose > 16.7 mmol/L were used as the model group and treated with Dendrobium mixture. (DEN ... Keywords: Diabetes, Gene expression, Dendrobium mixture, Microarray testing ..... homeostasis in airway smooth muscle. Am J.

  2. Identification of genes showing differential expression profile ...

    Indian Academy of Sciences (India)

    3Department of Natural Sciences, International Christian University, Mitaka, Tokyo 181-8585, Japan ... the changes of expression predicted from gene function suggested association ... ate School of Science and Technology, Niigata University.

  3. Drosophila melanogaster gene expression changes after spaceflight.

    Data.gov (United States)

    National Aeronautics and Space Administration — Gene expression levels were determined in 3rd instar and adult Drosophila melanogaster reared during spaceflight to elucidate the genetic and molecular mechanisms...

  4. Exertional Heat Illness and Human Gene Expression

    National Research Council Canada - National Science Library

    Sonna, L.A; Sawka, M. N; Lilly, C. M

    2007-01-01

    Microarray analysis of gene expression at the level of RNA has generated new insights into the relationship between cellular responses to acute heat shock in vitro, exercise, and exertional heat illness...

  5. Expression Profiling of Tyrosine Kinase Genes

    National Research Council Canada - National Science Library

    Weier, Heinz

    2000-01-01

    ... of these genes parallels the progression of tumors to a more malignant phenotype. We developed a DNA micro-array based screening system to monitor the level of expression of tyrosine kinase (tk...

  6. Regulation of meiotic gene expression in plants

    Directory of Open Access Journals (Sweden)

    Adele eZhou

    2014-08-01

    Full Text Available With the recent advances in genomics and sequencing technologies, databases of transcriptomes representing many cellular processes have been built. Meiotic transcriptomes in plants have been studied in Arabidopsis thaliana, rice (Oryza sativa, wheat (Triticum aestivum, petunia (Petunia hybrida, sunflower (Helianthus annuus, and maize (Zea mays. Studies in all organisms, but particularly in plants, indicate that a very large number of genes are expressed during meiosis, though relatively few of them seem to be required for the completion of meiosis. In this review, we focus on gene expression at the RNA level and analyze the meiotic transcriptome datasets and explore expression patterns of known meiotic genes to elucidate how gene expression could be regulated during meiosis. We also discuss mechanisms, such as chromatin organization and non-coding RNAs, that might be involved in the regulation of meiotic transcription patterns.

  7. Identification of genes preferentially expressed during

    African Journals Online (AJOL)

    雨林木风

    2012-08-16

    Aug 16, 2012 ... The suppression subtractive hybridization (SSH) method conducted to generate ... which showed the lack of genomic information currently available for lily. ..... characterization of genes expressed during somatic embryo.

  8. Mining gene expression data of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Pi Guo

    Full Text Available Microarray produces a large amount of gene expression data, containing various biological implications. The challenge is to detect a panel of discriminative genes associated with disease. This study proposed a robust classification model for gene selection using gene expression data, and performed an analysis to identify disease-related genes using multiple sclerosis as an example.Gene expression profiles based on the transcriptome of peripheral blood mononuclear cells from a total of 44 samples from 26 multiple sclerosis patients and 18 individuals with other neurological diseases (control were analyzed. Feature selection algorithms including Support Vector Machine based on Recursive Feature Elimination, Receiver Operating Characteristic Curve, and Boruta algorithms were jointly performed to select candidate genes associating with multiple sclerosis. Multiple classification models categorized samples into two different groups based on the identified genes. Models' performance was evaluated using cross-validation methods, and an optimal classifier for gene selection was determined.An overlapping feature set was identified consisting of 8 genes that were differentially expressed between the two phenotype groups. The genes were significantly associated with the pathways of apoptosis and cytokine-cytokine receptor interaction. TNFSF10 was significantly associated with multiple sclerosis. A Support Vector Machine model was established based on the featured genes and gave a practical accuracy of ∼86%. This binary classification model also outperformed the other models in terms of Sensitivity, Specificity and F1 score.The combined analytical framework integrating feature ranking algorithms and Support Vector Machine model could be used for selecting genes for other diseases.

  9. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis

    Science.gov (United States)

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

  10. Evaluation of suitable reference genes for gene expression studies ...

    Indian Academy of Sciences (India)

    2011-12-14

    Dec 14, 2011 ... MADS family of TFs control floral organ identity within each whorl of the flower by activating downstream genes. Measuring gene expression in different tissue types and developmental stages is of fundamental importance in TFs functional research. In last few years, quantitative real-time. PCR (qRT-PCR) ...

  11. PRAME gene expression profile in medulloblastoma

    Directory of Open Access Journals (Sweden)

    Tânia Maria Vulcani-Freitas

    2011-02-01

    Full Text Available Medulloblastoma is the most common malignant tumors of central nervous system in the childhood. The treatment is severe, harmful and, thus, has a dismal prognosis. As PRAME is present in various cancers, including meduloblastoma, and has limited expression in normal tissues, this antigen can be an ideal vaccine target for tumor immunotherapy. In order to find a potential molecular target, we investigated PRAME expression in medulloblastoma fragments and we compare the results with the clinical features of each patient. Analysis of gene expression was performed by real-time quantitative PCR from 37 tumor samples. The Mann-Whitney test was used to analysis the relationship between gene expression and clinical characteristics. Kaplan-Meier curves were used to evaluate survival. PRAME was overexpressed in 84% samples. But no statistical association was found between clinical features and PRAME overexpression. Despite that PRAME gene could be a strong candidate for immunotherapy since it is highly expressed in medulloblastomas.

  12. Comparative gene expression between two yeast species

    Directory of Open Access Journals (Sweden)

    Guan Yuanfang

    2013-01-01

    Full Text Available Abstract Background Comparative genomics brings insight into sequence evolution, but even more may be learned by coupling sequence analyses with experimental tests of gene function and regulation. However, the reliability of such comparisons is often limited by biased sampling of expression conditions and incomplete knowledge of gene functions across species. To address these challenges, we previously systematically generated expression profiles in Saccharomyces bayanus to maximize functional coverage as compared to an existing Saccharomyces cerevisiae data repository. Results In this paper, we take advantage of these two data repositories to compare patterns of ortholog expression in a wide variety of conditions. First, we developed a scalable metric for expression divergence that enabled us to detect a significant correlation between sequence and expression conservation on the global level, which previous smaller-scale expression studies failed to detect. Despite this global conservation trend, between-species gene expression neighborhoods were less well-conserved than within-species comparisons across different environmental perturbations, and approximately 4% of orthologs exhibited a significant change in co-expression partners. Furthermore, our analysis of matched perturbations collected in both species (such as diauxic shift and cell cycle synchrony demonstrated that approximately a quarter of orthologs exhibit condition-specific expression pattern differences. Conclusions Taken together, these analyses provide a global view of gene expression patterns between two species, both in terms of the conditions and timing of a gene's expression as well as co-expression partners. Our results provide testable hypotheses that will direct future experiments to determine how these changes may be specified in the genome.

  13. Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

    OpenAIRE

    Lasram, Khaled; Ben Halim, Nizar; Hsouna, Sana; Kefi, Rym; Arfa, Imen; Ghazouani, Welid; Jamoussi, Henda; Benrahma, Houda; Kharrat, Najla; Rebai, Ahmed; Ben Ammar, Slim; Bahri, Sonia; Barakat, Abdelhamid; Abid, Abdelmajid; Abdelhak, Sonia

    2014-01-01

    Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been ...

  14. Relationship between Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphism and Susceptibility of Minimal Change Nephrotic Syndrome: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Tian-Biao Zhou

    2011-01-01

    Africans: D: =.81, DD: =.49. Furthermore, the II genotype seemed not to play a protective role against MCNS risk for Asians, Caucasians and Africans (=.12, =.09, =.76, resp.. Interestingly, there was also significant association between ACE I/D gene polymorphism and MCNS susceptibility in overall populations (D: =.007, DD: =.04, II: =.03. Conclusion. D allele or DD genotype might be a significant genetic molecular marker for MCNS susceptibility in Asians and overall populations, but not for Caucasians and Africans. More larger and rigorous genetic epidemiological investigations are required to further explore this association.

  15. Meta-analysis of crowdsourced data compendia suggests pan-disease transcriptional signatures of autoimmunity [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    William W. Lau

    2016-12-01

    Full Text Available Background: The proliferation of publicly accessible large-scale biological data together with increasing availability of bioinformatics tools have the potential to transform biomedical research. Here we report a crowdsourcing Jamboree that explored whether a team of volunteer biologists without formal bioinformatics training could use OMiCC, a crowdsourcing web platform that facilitates the reuse and (meta- analysis of public gene expression data, to compile and annotate gene expression data, and design comparisons between disease and control sample groups. Methods: The Jamboree focused on several common human autoimmune diseases, including systemic lupus erythematosus (SLE, multiple sclerosis (MS, type I diabetes (DM1, and rheumatoid arthritis (RA, and the corresponding mouse models. Meta-analyses were performed in OMiCC using comparisons constructed by the participants to identify 1 gene expression signatures for each disease (disease versus healthy controls at the gene expression and biological pathway levels, 2 conserved signatures across all diseases within each species (pan-disease signatures, and 3 conserved signatures between species for each disease and across all diseases (cross-species signatures. Results: A large number of differentially expressed genes were identified for each disease based on meta-analysis, with observed overlap among diseases both within and across species. Gene set/pathway enrichment of upregulated genes suggested conserved signatures (e.g., interferon across all human and mouse conditions. Conclusions: Our Jamboree exercise provides evidence that when enabled by appropriate tools, a "crowd" of biologists can work together to accelerate the pace by which the increasingly large amounts of public data can be reused and meta-analyzed for generating and testing hypotheses. Our encouraging experience suggests that a similar crowdsourcing approach can be used to explore other biological questions.

  16. Inferring gene networks from discrete expression data

    KAUST Repository

    Zhang, L.

    2013-07-18

    The modeling of gene networks from transcriptional expression data is an important tool in biomedical research to reveal signaling pathways and to identify treatment targets. Current gene network modeling is primarily based on the use of Gaussian graphical models applied to continuous data, which give a closedformmarginal likelihood. In this paper,we extend network modeling to discrete data, specifically data from serial analysis of gene expression, and RNA-sequencing experiments, both of which generate counts of mRNAtranscripts in cell samples.We propose a generalized linear model to fit the discrete gene expression data and assume that the log ratios of the mean expression levels follow a Gaussian distribution.We restrict the gene network structures to decomposable graphs and derive the graphs by selecting the covariance matrix of the Gaussian distribution with the hyper-inverse Wishart priors. Furthermore, we incorporate prior network models based on gene ontology information, which avails existing biological information on the genes of interest. We conduct simulation studies to examine the performance of our discrete graphical model and apply the method to two real datasets for gene network inference. © The Author 2013. Published by Oxford University Press. All rights reserved.

  17. Gene expression profiling in autoimmune diseases

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo

    2007-01-01

    A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA...

  18. Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies

    Directory of Open Access Journals (Sweden)

    Jennifer A. Smith

    2017-12-01

    Full Text Available Inter-individual variability in blood pressure (BP is influenced by both genetic and non-genetic factors including socioeconomic and psychosocial stressors. A deeper understanding of the gene-by-socioeconomic/psychosocial factor interactions on BP may help to identify individuals that are genetically susceptible to high BP in specific social contexts. In this study, we used a genomic region-based method for longitudinal analysis, Longitudinal Gene-Environment-Wide Interaction Studies (LGEWIS, to evaluate the effects of interactions between known socioeconomic/psychosocial and genetic risk factors on systolic and diastolic BP in four large epidemiologic cohorts of European and/or African ancestry. After correction for multiple testing, two interactions were significantly associated with diastolic BP. In European ancestry participants, outward/trait anger score had a significant interaction with the C10orf107 genomic region (p = 0.0019. In African ancestry participants, depressive symptom score had a significant interaction with the HFE genomic region (p = 0.0048. This study provides a foundation for using genomic region-based longitudinal analysis to identify subgroups of the population that may be at greater risk of elevated BP due to the combined influence of genetic and socioeconomic/psychosocial risk factors.

  19. Bayesian assignment of gene ontology terms to gene expression experiments.

    Science.gov (United States)

    Sykacek, P

    2012-09-15

    Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Source code under GPL license is available from the author. peter.sykacek@boku.ac.at.

  20. Bayesian assignment of gene ontology terms to gene expression experiments

    Science.gov (United States)

    Sykacek, P.

    2012-01-01

    Motivation: Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. Results: This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Availability: Source code under GPL license is available from the author. Contact: peter.sykacek@boku.ac.at PMID:22962488

  1. Correlation between the Uptake of 18F-Fluorodeoxyglucose (18F-FDG) and the Expression of Proliferation-Associated Antigen Ki-67 in Cancer Patients: A Meta-Analysis.

    Science.gov (United States)

    Deng, Sheng-Ming; Zhang, Wei; Zhang, Bin; Chen, Yin-Yin; Li, Ji-Hui; Wu, Yi-Wei

    2015-01-01

    To study the correlation between 18F-FDG uptake and cell proliferation in cancer patients by meta-analysis of published articles. We searched PubMed (MEDLINE included), EMBASE, and Cochrane Database of Systematic Review, and selected research articles on the relationship between 18F-FDG uptake and Ki-67 expression (published between August 1, 1994-August 1, 2014), according to the literature inclusion and exclusion criteria. The publishing language was limited to English. The quality of included articles was evaluated according to the Quality Assessment of Diagnosis Accuracy Studies-2 (QUADAS-2). The correlation coefficient (r) was extracted from the included articles and processed by Fisher's r-to-z transformation. The combined correlation coefficient (r) and the 95% confidence interval (CI) were calculated with STATA 11.0 software under a random-effects model. Begg's test was used to analyze the existence of publication bias and draw funnel plot, and the sources of heterogeneity were explored by sensitivity and subgroup analyses. According to the inclusion and exclusion criteria, 79 articles were finally included, including 81 studies involving a total of 3242 patients. All the studies had a combined r of 0.44 (95% CI, 0.41-0.46), but with a significant heterogeneity (I2 = 80.9%, Ppositron emission tomography (PET) or PET/CT imaging technology or Ki-67 and standardized uptake value (SUV) measurement technology did not significantly affect the results of r values, and Begg's test showed no significant publication bias. In cancer patients, 18F-FDG uptake showed a moderate positive correlation with tumor cell proliferation. Different tumor types exhibited varied degree of correlation, and the correlation was significant in TETs and GSTs. However, our results need further validation by clinical trials with a large sample of different tumor types.

  2. The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis

    DEFF Research Database (Denmark)

    Saetre, Peter; Lundmark, Per; Wang, August

    2010-01-01

    Serotonin (5-hydroxytryptamin; 5-HT) alternations has since long been suspected in the pathophysiology of schizophrenia. Tryptophan hydroxylase (tryptophan 5-monooxygenase; TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT, and sequence variation in intron 6 of the TPH1 gene has been...... associated with schizophrenia. The minor allele (A) of this polymorphism (A218C) is also more frequent in patients who have attempted suicide and individuals who died by suicide, than in healthy control individuals. In an attempt to replicate previous findings, five single nucleotide polymorphisms (SNPs......) were genotyped in 837 Scandinavian schizophrenia patients and 1,473 controls. Three SNPs spanning intron 6 and 7, including the A218C and A779C polymorphisms, were associated with schizophrenia susceptibility (P = 0.019). However there were no differences in allele frequencies of these loci between...

  3. Meta-analysis diagnostic accuracy of SNP-based pathogenicity detection tools: a case of UTG1A1 gene mutations.

    Science.gov (United States)

    Galehdari, Hamid; Saki, Najmaldin; Mohammadi-Asl, Javad; Rahim, Fakher

    2013-01-01

    Crigler-Najjar syndrome (CNS) type I and type II are usually inherited as autosomal recessive conditions that result from mutations in the UGT1A1 gene. The main objective of the present review is to summarize results of all available evidence on the accuracy of SNP-based pathogenicity detection tools compared to published clinical result for the prediction of in nsSNPs that leads to disease using prediction performance method. A comprehensive search was performed to find all mutations related to CNS. Database searches included dbSNP, SNPdbe, HGMD, Swissvar, ensemble, and OMIM. All the mutation related to CNS was extracted. The pathogenicity prediction was done using SNP-based pathogenicity detection tools include SIFT, PHD-SNP, PolyPhen2, fathmm, Provean, and Mutpred. Overall, 59 different SNPs related to missense mutations in the UGT1A1 gene, were reviewed. Comparing the diagnostic OR, PolyPhen2 and Mutpred have the highest detection 4.983 (95% CI: 1.24 - 20.02) in both, following by SIFT (diagnostic OR: 3.25, 95% CI: 1.07 - 9.83). The highest MCC of SNP-based pathogenicity detection tools, was belong to SIFT (34.19%) followed by Provean, PolyPhen2, and Mutpred (29.99%, 29.89%, and 29.89%, respectively). Hence the highest SNP-based pathogenicity detection tools ACC, was fit to SIFT (62.71%) followed by PolyPhen2, and Mutpred (61.02%, in both). Our results suggest that some of the well-established SNP-based pathogenicity detection tools can appropriately reflect the role of a disease-associated SNP in both local and global structures.

  4. Long non-coding RNA TUG1 as a potential prognostic biomarker in human cancers: a meta-analysis.

    Science.gov (United States)

    Ma, Peng-Ju; Guan, Qing-Kai; Meng, Lei; Qin, Nan; Zhao, Jia; Jin, Bao-Zhe

    2017-09-22

    LncRNA taurine upregulated gene 1 (TUG1) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the usefulness of TUG1 as a prognostic marker in malignant tumors. The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to Jan 11, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between TUG1 expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between TUG1 expression and pathological parameters. Thirteen original studies covering 1,274 cancer patients were included in this meta-analysis. The pooled HR suggested that high TUG1 expression correlated with poor OS (pooled HR=1.41, 95% CI: 1.01-1.98) in cancer types other than non-small cell lung cancer. TUG1 expression was also related to distant metastasis (OR=3.24, 95% CI: 1.18-8.93), large tumor size (OR=4.07, 95% CI: 1.08-15.28) and advanced tumor stage (OR=3.45, 95% CI: 2.19-5.44). Begg's funnel plot and Egger's test showed no evidence of obvious asymmetry for overall survival or tumor stage. Thus high TUG1 expression appears predictive of poor OS, distant metastasis, advanced tumor stage and large tumor size. This suggests TUG1 expression could serve as a biomarker for poor prognosis in cancers.

  5. Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2013-12-01

    Full Text Available Real-time quantitative PCR (qRT-PCR is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2 in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

  6. Conducting Meta-Analysis Using SAS

    CERN Document Server

    Arthur, Winfried; Huffcutt, Allen I; Arthur, Winfred

    2001-01-01

    Conducting Meta-Analysis Using SAS reviews the meta-analysis statistical procedure and shows the reader how to conduct one using SAS. It presents and illustrates the use of the PROC MEANS procedure in SAS to perform the data computations called for by the two most commonly used meta-analytic procedures, the Hunter & Schmidt and Glassian approaches. This book serves as both an operational guide and user's manual by describing and explaining the meta-analysis procedures and then presenting the appropriate SAS program code for computing the pertinent statistics. The practical, step-by-step instru

  7. Correlation between the Uptake of 18F-Fluorodeoxyglucose (18F-FDG and the Expression of Proliferation-Associated Antigen Ki-67 in Cancer Patients: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Sheng-Ming Deng

    Full Text Available To study the correlation between 18F-FDG uptake and cell proliferation in cancer patients by meta-analysis of published articles.We searched PubMed (MEDLINE included, EMBASE, and Cochrane Database of Systematic Review, and selected research articles on the relationship between 18F-FDG uptake and Ki-67 expression (published between August 1, 1994-August 1, 2014, according to the literature inclusion and exclusion criteria. The publishing language was limited to English. The quality of included articles was evaluated according to the Quality Assessment of Diagnosis Accuracy Studies-2 (QUADAS-2. The correlation coefficient (r was extracted from the included articles and processed by Fisher's r-to-z transformation. The combined correlation coefficient (r and the 95% confidence interval (CI were calculated with STATA 11.0 software under a random-effects model. Begg's test was used to analyze the existence of publication bias and draw funnel plot, and the sources of heterogeneity were explored by sensitivity and subgroup analyses.According to the inclusion and exclusion criteria, 79 articles were finally included, including 81 studies involving a total of 3242 patients. All the studies had a combined r of 0.44 (95% CI, 0.41-0.46, but with a significant heterogeneity (I2 = 80.9%, P<0.01. Subgroup analysis for different tumor types indicated that most subgroups showed a reduced heterogeneity. Malignant melanoma (n = 1 had the minimum correlation coefficient (-0.22 between 18F-FDG uptake and Ki-67 expression, while the thymic epithelial tumors (TETs; n = 2 showed the maximum correlation coefficient of 0.81. The analytical results confirmed that correlation between 18F-FDG uptake and Ki-67 expression was extremely significant in TETs, significant in gastrointestinal stromal tumors (GISTs, moderate in patients with lung, breast, bone and soft tissue, pancreatic, oral, thoracic, and uterine and ovarian cancers, average in brain, esophageal and colorectal

  8. Noise minimization in eukaryotic gene expression.

    Directory of Open Access Journals (Sweden)

    Hunter B Fraser

    2004-06-01

    Full Text Available All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or "noise." Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.

  9. Noise minimization in eukaryotic gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Hirsh, Aaron E.; Giaever, Guri; Kumm, Jochen; Eisen, Michael B.

    2004-01-15

    All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or noise. Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.

  10. Noise minimization in eukaryotic gene expression

    International Nuclear Information System (INIS)

    Fraser, Hunter B.; Hirsh, Aaron E.; Giaever, Guri; Kumm, Jochen; Eisen, Michael B.

    2004-01-01

    All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or noise. Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  12. Gene expression in triple-negative breast cancer in relation to survival.

    Science.gov (United States)

    Wang, Shuyang; Beeghly-Fadiel, Alicia; Cai, Qiuyin; Cai, Hui; Guo, Xingyi; Shi, Liang; Wu, Jie; Ye, Fei; Qiu, Qingchao; Zheng, Ying; Zheng, Wei; Bao, Ping-Ping; Shu, Xiao-Ou

    2018-05-10

    The identification of biomarkers related to the prognosis of triple-negative breast cancer (TNBC) is critically important for improved understanding of the biology that drives TNBC progression. We evaluated gene expression in total RNA isolated from formalin-fixed paraffin-embedded tumor samples using the NanoString nCounter assay for 469 TNBC cases from the Shanghai Breast Cancer Survival Study. We used Cox regression to quantify Hazard Ratios (HR) and corresponding confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS) in models that included adjustment for breast cancer intrinsic subtype. Of 302 genes in our discovery analysis, 22 were further evaluated in relation to OS among 134 TNBC cases from the Nashville Breast Health Study and the Southern Community Cohort Study; 16 genes were further evaluated in relation to DFS in 335 TNBC cases from four gene expression omnibus datasets. Fixed-effect meta-analysis was used to combine results across data sources. Twofold higher expression of EOMES (HR 0.90, 95% CI 0.83-0.97), RASGRP1 (HR 0.89, 95% CI 0.82-0.97), and SOD2 (HR 0.80, 95% CI 0.66-0.96) was associated with better OS. Twofold higher expression of EOMES (HR 0.89, 95% CI 0.81-0.97) and RASGRP1 (HR 0.87, 95% CI 0.81-0.95) was also associated with better DFS. On the contrary, a doubling of FA2H (HR 1.14, 95% CI 1.06-1.22) and GSPT1 (HR 1.33, 95% CI 1.14-1.55) expression was associated with shorter DFS. We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.

  13. Physical Readiness Training: A Meta-Analysis

    National Research Council Canada - National Science Library

    Vickers, Jr, Ross R

    2007-01-01

    .... This meta-analysis of available PRT studies (k = 3) indicated that (a) Fitness gains in the PRT program were equal to the gains in traditional fitness programs, and (b) the injury rate (i.e., hazard ratio...

  14. Exercise and Bone Density: Meta-Analysis

    National Research Council Canada - National Science Library

    Kelley, George A; Sharpe-Kelley, Kristi

    2007-01-01

    .... Since no meta-analysis had existed using individual patient data (IPD) to examine the effects of exercise on BMD, our second two-year period of funding was devoted to examining the feasibility...

  15. Microarray Meta-Analysis of RNA-Binding Protein Functions in Alternative Polyadenylation

    Science.gov (United States)

    Hu, Wenchao; Liu, Yuting; Yan, Jun

    2014-01-01

    Alternative polyadenylation (APA) is a post-transcriptional mechanism to generate diverse mRNA transcripts with different 3′UTRs from the same gene. In this study, we systematically searched for the APA events with differential expression in public mouse microarray data. Hundreds of genes with over-represented differential APA events and the corresponding experiments were identified. We further revealed that global APA differential expression occurred prevalently in tissues such as brain comparing to peripheral tissues, and biological processes such as development, differentiation and immune responses. Interestingly, we also observed widespread differential APA events in RNA-binding protein (RBP) genes such as Rbm3, Eif4e2 and Elavl1. Given the fact that RBPs are considered as the main regulators of differential APA expression, we constructed a co-expression network between APAs and RBPs using the microarray data. Further incorporation of CLIP-seq data of selected RBPs showed that Nova2 represses and Mbnl1 promotes the polyadenylation of closest poly(A) sites respectively. Altogether, our study is the first microarray meta-analysis in a mammal on the regulation of APA by RBPs that integrated massive mRNA expression data under a wide-range of biological conditions. Finally, we present our results as a comprehensive resource in an online website for the research community. PMID:24622240

  16. Expression Study of Banana Pathogenic Resistance Genes

    Directory of Open Access Journals (Sweden)

    Fenny M. Dwivany

    2016-10-01

    Full Text Available Banana is one of the world's most important trade commodities. However, infection of banana pathogenic fungi (Fusarium oxysporum race 4 is one of the major causes of decreasing production in Indonesia. Genetic engineering has become an alternative way to control this problem by isolating genes that involved in plant defense mechanism against pathogens. Two of the important genes are API5 and ChiI1, each gene encodes apoptosis inhibitory protein and chitinase enzymes. The purpose of this study was to study the expression of API5 and ChiI1 genes as candidate pathogenic resistance genes. The amplified fragments were then cloned, sequenced, and confirmed with in silico studies. Based on sequence analysis, it is showed that partial API5 gene has putative transactivation domain and ChiI1 has 9 chitinase family GH19 protein motifs. Data obtained from this study will contribute in banana genetic improvement.

  17. Dlx homeobox gene family expression in osteoclasts.

    Science.gov (United States)

    Lézot, F; Thomas, B L; Blin-Wakkach, C; Castaneda, B; Bolanos, A; Hotton, D; Sharpe, P T; Heymann, D; Carles, G F; Grigoriadis, A E; Berdal, A

    2010-06-01

    Skeletal growth and homeostasis require the finely orchestrated secretion of mineralized tissue matrices by highly specialized cells, balanced with their degradation by osteoclasts. Time- and site-specific expression of Dlx and Msx homeobox genes in the cells secreting these matrices have been identified as important elements in the regulation of skeletal morphology. Such specific expression patterns have also been reported in osteoclasts for Msx genes. The aim of the present study was to establish the expression patterns of Dlx genes in osteoclasts and identify their function in regulating skeletal morphology. The expression patterns of all Dlx genes were examined during the whole osteoclastogenesis using different in vitro models. The results revealed that Dlx1 and Dlx2 are the only Dlx family members with a possible function in osteoclastogenesis as well as in mature osteoclasts. Dlx5 and Dlx6 were detected in the cultures but appear to be markers of monocytes and their derivatives. In vivo, Dlx2 expression in osteoclasts was examined using a Dlx2/LacZ transgenic mouse. Dlx2 is expressed in a subpopulation of osteoclasts in association with tooth, brain, nerve, and bone marrow volumetric growths. Altogether the present data suggest a role for Dlx2 in regulation of skeletal morphogenesis via functions within osteoclasts. (c) 2010 Wiley-Liss, Inc.

  18. Hepatocyte specific expression of human cloned genes

    Energy Technology Data Exchange (ETDEWEB)

    Cortese, R

    1986-01-01

    A large number of proteins are specifically synthesized in the hepatocyte. Only the adult liver expresses the complete repertoire of functions which are required at various stages during development. There is therefore a complex series of regulatory mechanisms responsible for the maintenance of the differentiated state and for the developmental and physiological variations in the pattern of gene expression. Human hepatoma cell lines HepG2 and Hep3B display a pattern of gene expression similar to adult and fetal liver, respectively; in contrast, cultured fibroblasts or HeLa cells do not express most of the liver specific genes. They have used these cell lines for transfection experiments with cloned human liver specific genes. DNA segments coding for alpha1-antitrypsin and retinol binding protein (two proteins synthesized both in fetal and adult liver) are expressed in the hepatoma cell lines HepG2 and Hep3B, but not in HeLa cells or fibroblasts. A DNA segment coding for haptoglobin (a protein synthesized only after birth) is only expressed in the hepatoma cell line HepG2 but not in Hep3B nor in non hepatic cell lines. The information for tissue specific expression is located in the 5' flanking region of all three genes. In vivo competition experiments show that these DNA segments bind to a common, apparently limiting, transacting factor. Conventional techniques (Bal deletions, site directed mutagenesis, etc.) have been used to precisely identify the DNA sequences responsible for these effects. The emerging picture is complex: they have identified multiple, separate transcriptional signals, essential for maximal promoter activation and tissue specific expression. Some of these signals show a negative effect on transcription in fibroblast cell lines.

  19. Gene expression profiles in skeletal muscle after gene electrotransfer

    DEFF Research Database (Denmark)

    Hojman, Pernille; Zibert, John R; Gissel, Hanne

    2007-01-01

    BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...... caused down-regulation of structural proteins e.g. sarcospan and catalytic enzymes. Injection of DNA induced down-regulation of intracellular transport proteins e.g. sentrin. The effects on muscle fibres were transient as the expression profiles 3 weeks after treatment were closely related......) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. RESULTS: Differentially expressed genes were...

  20. Gene expression analysis of flax seed development

    Science.gov (United States)

    2011-01-01

    Background Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. Results We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages) seed coats (globular and torpedo stages) and endosperm (pooled globular to torpedo stages) and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST) (GenBank accessions LIBEST_026995 to LIBEST_027011) were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152) had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. Conclusions We have developed a foundational database of expressed sequences and collection of plasmid clones that comprise

  1. Gene expression analysis of flax seed development

    Directory of Open Access Journals (Sweden)

    Sharpe Andrew

    2011-04-01

    Full Text Available Abstract Background Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. Results We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages seed coats (globular and torpedo stages and endosperm (pooled globular to torpedo stages and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST (GenBank accessions LIBEST_026995 to LIBEST_027011 were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152 had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. Conclusions We have developed a foundational database of expressed sequences and collection of plasmid

  2. Genetic Polymorphism of Angiotensin-Converting Enzyme and Chronic Obstructive Pulmonary Disease Risk: An Updated Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Sang Wook Kang

    2016-01-01

    Full Text Available The relationship between polymorphism of the angiotensin I converting enzyme (ACE gene and chronic obstructive pulmonary disease (COPD has been examined in many previous studies. However, their results were controversial. Therefore, we performed a meta-analysis to evaluate the relationship between the ACE gene and the risk of COPD. Fourteen case-control studies were included in this meta-analysis. The pooled p value, odds ratio (OR, and 95% confidence interval (95% CI were used to investigate the strength of the association. The meta-analysis was performed using comprehensive meta-analysis software. Our meta-analysis results revealed that ACE polymorphisms were not related to the risk of COPD (p>0.05 in each model. In further analyses based on ethnicity, we observed an association between insertion/deletion polymorphism of the ACE gene and risk of COPD in the Asian population (codominant 2, OR = 3.126, 95% CI = 1.919–5.093, p0.05 in each model. In conclusion, the present meta-analysis indicated that the insertion/deletion polymorphism of the ACE gene may be associated with susceptibility to COPD in the Asian population but not in the Caucasian population. However, the results of the present meta-analysis need to be confirmed in a larger sample.

  3. Lithium ions induce prestalk-associated gene expression and inhibit prespore gene expression in Dictyostelium discoideum

    NARCIS (Netherlands)

    Peters, Dorien J.M.; Lookeren Campagne, Michiel M. van; Haastert, Peter J.M. van; Spek, Wouter; Schaap, Pauline

    1989-01-01

    We investigated the effect of Li+ on two types of cyclic AMP-regulated gene expression and on basal and cyclic AMP-stimulated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) levels. Li+ effectively inhibits cyclic AMP-induced prespore gene expression, half-maximal inhibition occurring at about 2mM-LiCl.

  4. Scaling of gene expression data allowing the comparison of different gene expression platforms

    NARCIS (Netherlands)

    van Ruissen, Fred; Schaaf, Gerben J.; Kool, Marcel; Baas, Frank; Ruijter, Jan M.

    2008-01-01

    Serial analysis of gene expression (SAGE) and microarrays have found a widespread application, but much ambiguity exists regarding the amalgamation of the data resulting from these technologies. Cross-platform utilization of gene expression data from the SAGE and microarray technology could reduce

  5. Meta-analysis of breast cancer microarray studies in conjunction with conserved cis-elements suggest patterns for coordinate regulation

    Directory of Open Access Journals (Sweden)

    Lundberg Cathryn

    2008-01-01

    Full Text Available Abstract Background Gene expression measurements from breast cancer (BrCa tumors are established clinical predictive tools to identify tumor subtypes, identify patients showing poor/good prognosis, and identify patients likely to have disease recurrence. However, diverse breast cancer datasets in conjunction with diagnostic clinical arrays show little overlap in the sets of genes identified. One approach to identify a set of consistently dysregulated candidate genes in these tumors is to employ meta-analysis of multiple independent microarray datasets. This allows one to compare expression data from a diverse collection of breast tumor array datasets generated on either cDNA or oligonucleotide arrays. Results We gathered expression data from 9 published microarray studies examining estrogen receptor positive (ER+ and estrogen receptor negative (ER- BrCa tumor cases from the Oncomine database. We performed a meta-analysis and identified genes that were universally up or down regulated with respect to ER+ versus ER- tumor status. We surveyed both the proximal promoter and 3' untranslated regions (3'UTR of our top-ranking genes in each expression group to test whether common sequence elements may contribute to the observed expression patterns. Utilizing a combination of known transcription factor binding sites (TFBS, evolutionarily conserved mammalian promoter and 3'UTR motifs, and microRNA (miRNA seed sequences, we identified numerous motifs that were disproportionately represented between the two gene classes suggesting a common regulatory network for the observed gene expression patterns. Conclusion Some of the genes we identified distinguish key transcripts previously seen in array studies, while others are newly defined. Many of the genes identified as overexpressed in ER- tumors were previously identified as expression markers for neoplastic transformation in multiple human cancers. Moreover, our motif analysis identified a collection of

  6. Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease.

    Science.gov (United States)

    Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

    2014-01-01

    We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. http://rged.wall-eva.net. © The Author(s) 2014. Published by Oxford University Press.

  7. Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

    Science.gov (United States)

    Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

    2014-01-01

    We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

  8. Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

    Science.gov (United States)

    van Uitert, Miranda; Moerland, Perry D; Enquobahrie, Daniel A; Laivuori, Hannele; van der Post, Joris A M; Ris-Stalpers, Carrie; Afink, Gijs B

    2015-01-01

    Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

  9. Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Miranda van Uitert

    Full Text Available Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite and protein-protein associations (STRING. This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome. The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300 and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

  10. Strategies for comparing gene expression profiles from different microarray platforms: application to a case-control experiment.

    Science.gov (United States)

    Severgnini, Marco; Bicciato, Silvio; Mangano, Eleonora; Scarlatti, Francesca; Mezzelani, Alessandra; Mattioli, Michela; Ghidoni, Riccardo; Peano, Clelia; Bonnal, Raoul; Viti, Federica; Milanesi, Luciano; De Bellis, Gianluca; Battaglia, Cristina

    2006-06-01

    Meta-analysis of microarray data is increasingly important, considering both the availability of multiple platforms using disparate technologies and the accumulation in public repositories of data sets from different laboratories. We addressed the issue of comparing gene expression profiles from two microarray platforms by devising a standardized investigative strategy. We tested this procedure by studying MDA-MB-231 cells, which undergo apoptosis on treatment with resveratrol. Gene expression profiles were obtained using high-density, short-oligonucleotide, single-color microarray platforms: GeneChip (Affymetrix) and CodeLink (Amersham). Interplatform analyses were carried out on 8414 common transcripts represented on both platforms, as identified by LocusLink ID, representing 70.8% and 88.6% of annotated GeneChip and CodeLink features, respectively. We identified 105 differentially expressed genes (DEGs) on CodeLink and 42 DEGs on GeneChip. Among them, only 9 DEGs were commonly identified by both platforms. Multiple analyses (BLAST alignment of probes with target sequences, gene ontology, literature mining, and quantitative real-time PCR) permitted us to investigate the factors contributing to the generation of platform-dependent results in single-color microarray experiments. An effective approach to cross-platform comparison involves microarrays of similar technologies, samples prepared by identical methods, and a standardized battery of bioinformatic and statistical analyses.

  11. 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.

  12. Meta-analysis reveals host-dependent nitrogen recycling as a mechanism of symbiont control in Aiptasia

    KAUST Repository

    Cui, Guoxin; Liew, Yi Jin; Li, Yong; Kharbatia, Najeh M.; Zahran, Noura Ibrahim Omar; Emwas, Abdul-Hamid M.; Eguí luz, Ví ctor M; Aranda, Manuel

    2018-01-01

    in the emerging model organism Aiptasia. However, previous studies identified thousands of putatively symbiosis-related genes, making it difficult to disentangle symbiosis-induced responses from undesired experimental parameters. Using a meta-analysis approach, we

  13. Meta-Analysis of Transcriptional Responses to Mastitis-Causing Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Sidra Younis

    Full Text Available Bovine mastitis is a widespread disease in dairy cows, and is often caused by bacterial mammary gland infection. Mastitis causes reduced milk production and leads to excessive use of antibiotics. We present meta-analysis of transcriptional profiles of bovine mastitis from 10 studies and 307 microarrays, allowing identification of much larger sets of affected genes than any individual study. Combining multiple studies provides insight into the molecular effects of Escherichia coli infection in vivo and uncovers differences between the consequences of E. coli vs. Staphylococcus aureus infection of primary mammary epithelial cells (PMECs. In udders, live E. coli elicits inflammatory and immune defenses through numerous cytokines and chemokines. Importantly, E. coli infection causes downregulation of genes encoding lipid biosynthesis enzymes that are involved in milk production. Additionally, host metabolism is generally suppressed. Finally, defensins and bacteria-recognition genes are upregulated, while the expression of the extracellular matrix protein transcripts is silenced. In PMECs, heat-inactivated E. coli elicits expression of ribosomal, cytoskeletal and angiogenic signaling genes, and causes suppression of the cell cycle and energy production genes. We hypothesize that heat-inactivated E. coli may have prophylactic effects against mastitis. Heat-inactivated S. aureus promotes stronger inflammatory and immune defenses than E. coli. Lipopolysaccharide by itself induces MHC antigen presentation components, an effect not seen in response to E. coli bacteria. These results provide the basis for strategies to prevent and treat mastitis and may lead to the reduction in the use of antibiotics.

  14. Genome-wide meta-analysis identifies new susceptibility loci for migraine.

    Science.gov (United States)

    Anttila, Verneri; Winsvold, Bendik S; Gormley, Padhraig; Kurth, Tobias; Bettella, Francesco; McMahon, George; Kallela, Mikko; Malik, Rainer; de Vries, Boukje; Terwindt, Gisela; Medland, Sarah E; Todt, Unda; McArdle, Wendy L; Quaye, Lydia; Koiranen, Markku; Ikram, M Arfan; Lehtimäki, Terho; Stam, Anine H; Ligthart, Lannie; Wedenoja, Juho; Dunham, Ian; Neale, Benjamin M; Palta, Priit; Hamalainen, Eija; Schürks, Markus; Rose, Lynda M; Buring, Julie E; Ridker, Paul M; Steinberg, Stacy; Stefansson, Hreinn; Jakobsson, Finnbogi; Lawlor, Debbie A; Evans, David M; Ring, Susan M; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari A; Freilinger, Tobias; Schoenen, Jean; Frants, Rune R; Pelzer, Nadine; Weller, Claudia M; Zielman, Ronald; Heath, Andrew C; Madden, Pamela A F; Montgomery, Grant W; Martin, Nicholas G; Borck, Guntram; Göbel, Hartmut; Heinze, Axel; Heinze-Kuhn, Katja; Williams, Frances M K; Hartikainen, Anna-Liisa; Pouta, Anneli; van den Ende, Joyce; Uitterlinden, Andre G; Hofman, Albert; Amin, Najaf; Hottenga, Jouke-Jan; Vink, Jacqueline M; Heikkilä, Kauko; Alexander, Michael; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Wichmann, Heinz Erich; Aromaa, Arpo; Eriksson, Johan G; Traynor, Bryan; Trabzuni, Daniah; Rossin, Elizabeth; Lage, Kasper; Jacobs, Suzanne B R; Gibbs, J Raphael; Birney, Ewan; Kaprio, Jaakko; Penninx, Brenda W; Boomsma, Dorret I; van Duijn, Cornelia; Raitakari, Olli; Jarvelin, Marjo-Riitta; Zwart, John-Anker; Cherkas, Lynn; Strachan, David P; Kubisch, Christian; Ferrari, Michel D; van den Maagdenberg, Arn M J M; Dichgans, Martin; Wessman, Maija; Smith, George Davey; Stefansson, Kari; Daly, Mark J; Nyholt, Dale R; Chasman, Daniel; Palotie, Aarno

    2013-08-01

    Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P<5×10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.

  15. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata

    2015-01-01

    Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gen...

  16. Meta-Analysis of Maternal and Fetal Transcriptomic Data Elucidates the Role of Adaptive and Innate Immunity in Preterm Birth

    Science.gov (United States)

    Vora, Bianca; Wang, Aolin; Kosti, Idit; Huang, Hongtai; Paranjpe, Ishan; Woodruff, Tracey J.; MacKenzie, Tippi; Sirota, Marina

    2018-01-01

    Preterm birth (PTB) is the leading cause of newborn deaths around the world. Spontaneous preterm birth (sPTB) accounts for two-thirds of all PTBs; however, there remains an unmet need of detecting and preventing sPTB. Although the dysregulation of the immune system has been implicated in various studies, small sizes and irreproducibility of results have limited identification of its role. Here, we present a cross-study meta-analysis to evaluate genome-wide differential gene expression signals in sPTB. A comprehensive search of the NIH genomic database for studies related to sPTB with maternal whole blood samples resulted in data from three separate studies consisting of 339 samples. After aggregating and normalizing these transcriptomic datasets and performing a meta-analysis, we identified 210 genes that were differentially expressed in sPTB relative to term birth. These genes were enriched in immune-related pathways, showing upregulation of innate immunity and downregulation of adaptive immunity in women who delivered preterm. An additional analysis found several of these differentially expressed at mid-gestation, suggesting their potential to be clinically relevant biomarkers. Furthermore, a complementary analysis identified 473 genes differentially expressed in preterm cord blood samples. However, these genes demonstrated downregulation of the innate immune system, a stark contrast to findings using maternal blood samples. These immune-related findings were further confirmed by cell deconvolution as well as upstream transcription and cytokine regulation analyses. Overall, this study identified a strong immune signature related to sPTB as well as several potential biomarkers that could be translated to clinical use.

  17. Meta-Analysis of Maternal and Fetal Transcriptomic Data Elucidates the Role of Adaptive and Innate Immunity in Preterm Birth

    Directory of Open Access Journals (Sweden)

    Bianca Vora

    2018-05-01

    Full Text Available Preterm birth (PTB is the leading cause of newborn deaths around the world. Spontaneous preterm birth (sPTB accounts for two-thirds of all PTBs; however, there remains an unmet need of detecting and preventing sPTB. Although the dysregulation of the immune system has been implicated in various studies, small sizes and irreproducibility of results have limited identification of its role. Here, we present a cross-study meta-analysis to evaluate genome-wide differential gene expression signals in sPTB. A comprehensive search of the NIH genomic database for studies related to sPTB with maternal whole blood samples resulted in data from three separate studies consisting of 339 samples. After aggregating and normalizing these transcriptomic datasets and performing a meta-analysis, we identified 210 genes that were differentially expressed in sPTB relative to term birth. These genes were enriched in immune-related pathways, showing upregulation of innate immunity and downregulation of adaptive immunity in women who delivered preterm. An additional analysis found several of these differentially expressed at mid-gestation, suggesting their potential to be clinically relevant biomarkers. Furthermore, a complementary analysis identified 473 genes differentially expressed in preterm cord blood samples. However, these genes demonstrated downregulation of the innate immune system, a stark contrast to findings using maternal blood samples. These immune-related findings were further confirmed by cell deconvolution as well as upstream transcription and cytokine regulation analyses. Overall, this study identified a strong immune signature related to sPTB as well as several potential biomarkers that could be translated to clinical use.

  18. Metallothionein gene expression in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Deeksha Pal

    2014-01-01

    Full Text Available Introduction: Metallothioneins (MTs are a group of low-molecular weight, cysteine-rich proteins. In general, MT is known to modulate three fundamental processes: (1 the release of gaseous mediators such as hydroxyl radical or nitric oxide, (2 apoptosis and (3 the binding and exchange of heavy metals such as zinc, cadmium or copper. Previous studies have shown a positive correlation between the expression of MT with invasion, metastasis and poor prognosis in various cancers. Most of the previous studies primarily used immunohistochemistry to analyze localization of MT in renal cell carcinoma (RCC. No information is available on the gene expression of MT2A isoform in different types and grades of RCC. Materials and Methods: In the present study, total RNA was isolated from 38 histopathologically confirmed cases of RCC of different types and grades. Corresponding adjacent normal renal parenchyma was taken as control. Real-time polymerase chain reaction (RT PCR analysis was done for the MT2A gene expression using b-actin as an internal control. All statistical calculations were performed using SPSS software. Results: The MT2A gene expression was found to be significantly increased (P < 0.01 in clear cell RCC in comparison with the adjacent normal renal parenchyma. The expression of MT2A was two to three-fold higher in sarcomatoid RCC, whereas there was no change in papillary and collecting duct RCC. MT2A gene expression was significantly higher in lower grade (grades I and II, P < 0.05, while no change was observed in high-grade tumor (grade III and IV in comparison to adjacent normal renal tissue. Conclusion: The first report of the expression of MT2A in different types and grades of RCC and also these data further support the role of MT2A in tumorigenesis.

  19. Gene expression of the endolymphatic sac

    DEFF Research Database (Denmark)

    Friis, Morten; Martin-Bertelsen, Tomas; Friis-Hansen, Lennart

    2011-01-01

    that the endolymphatic sac has multiple and diverse functions in the inner ear. Objectives:The objective of this study was to provide a comprehensive review of the genes expressed in the endolymphatic sac in the rat and perform a functional characterization based on measured mRNA abundance. Methods:Microarray technology...

  20. Gene expression in early stage cervical cancer

    NARCIS (Netherlands)

    Biewenga, Petra; Buist, Marrije R.; Moerland, Perry D.; van Thernaat, Emiel Ver Loren; van Kampen, Antoine H. C.; ten Kate, Fiebo J. W.; Baas, Frank

    2008-01-01

    Objective. Pelvic lymph node metastases are the main prognostic factor for survival in early stage cervical cancer, yet accurate detection methods before surgery are lacking. In this study, we examined whether gene expression profiling can predict the presence of lymph node metastasis in early stage

  1. Shrinkage Approach for Gene Expression Data Analysis

    Czech Academy of Sciences Publication Activity Database

    Haman, Jiří; Valenta, Zdeněk; Kalina, Jan

    2013-01-01

    Roč. 1, č. 1 (2013), s. 65-65 ISSN 1805-8698. [EFMI 2013 Special Topic Conference. 17.04.2013-19.04.2013, Prague] Institutional support: RVO:67985807 Keywords : shrinkage estimation * covariance matrix * high dimensional data * gene expression Subject RIV: IN - Informatics, Computer Science

  2. Regulation of methane genes and genome expression

    Energy Technology Data Exchange (ETDEWEB)

    John N. Reeve

    2009-09-09

    At the start of this project, it was known that methanogens were Archaeabacteria (now Archaea) and were therefore predicted to have gene expression and regulatory systems different from Bacteria, but few of the molecular biology details were established. The goals were then to establish the structures and organizations of genes in methanogens, and to develop the genetic technologies needed to investigate and dissect methanogen gene expression and regulation in vivo. By cloning and sequencing, we established the gene and operon structures of all of the “methane” genes that encode the enzymes that catalyze methane biosynthesis from carbon dioxide and hydrogen. This work identified unique sequences in the methane gene that we designated mcrA, that encodes the largest subunit of methyl-coenzyme M reductase, that could be used to identify methanogen DNA and establish methanogen phylogenetic relationships. McrA sequences are now the accepted standard and used extensively as hybridization probes to identify and quantify methanogens in environmental research. With the methane genes in hand, we used northern blot and then later whole-genome microarray hybridization analyses to establish how growth phase and substrate availability regulated methane gene expression in Methanobacterium thermautotrophicus ΔH (now Methanothermobacter thermautotrophicus). Isoenzymes or pairs of functionally equivalent enzymes catalyze several steps in the hydrogen-dependent reduction of carbon dioxide to methane. We established that hydrogen availability determine which of these pairs of methane genes is expressed and therefore which of the alternative enzymes is employed to catalyze methane biosynthesis under different environmental conditions. As were unable to establish a reliable genetic system for M. thermautotrophicus, we developed in vitro transcription as an alternative system to investigate methanogen gene expression and regulation. This led to the discovery that an archaeal protein

  3. Fluid Mechanics, Arterial Disease, and Gene Expression.

    Science.gov (United States)

    Tarbell, John M; Shi, Zhong-Dong; Dunn, Jessilyn; Jo, Hanjoong

    2014-01-01

    This review places modern research developments in vascular mechanobiology in the context of hemodynamic phenomena in the cardiovascular system and the discrete localization of vascular disease. The modern origins of this field are traced, beginning in the 1960s when associations between flow characteristics, particularly blood flow-induced wall shear stress, and the localization of atherosclerotic plaques were uncovered, and continuing to fluid shear stress effects on the vascular lining endothelial) cells (ECs), including their effects on EC morphology, biochemical production, and gene expression. The earliest single-gene studies and genome-wide analyses are considered. The final section moves from the ECs lining the vessel wall to the smooth muscle cells and fibroblasts within the wall that are fluid me chanically activated by interstitial flow that imposes shear stresses on their surfaces comparable with those of flowing blood on EC surfaces. Interstitial flow stimulates biochemical production and gene expression, much like blood flow on ECs.

  4. Comparative gene expression of intestinal metabolizing enzymes.

    Science.gov (United States)

    Shin, Ho-Chul; Kim, Hye-Ryoung; Cho, Hee-Jung; Yi, Hee; Cho, Soo-Min; Lee, Dong-Goo; Abd El-Aty, A M; Kim, Jin-Suk; Sun, Duxin; Amidon, Gordon L

    2009-11-01

    The purpose of this study was to compare the expression profiles of drug-metabolizing enzymes in the intestine of mouse, rat and human. Total RNA was isolated from the duodenum and the mRNA expression was measured using Affymetrix GeneChip oligonucleotide arrays. Detected genes from the intestine of mouse, rat and human were ca. 60% of 22690 sequences, 40% of 8739 and 47% of 12559, respectively. Total genes of metabolizing enzymes subjected in this study were 95, 33 and 68 genes in mouse, rat and human, respectively. Of phase I enzymes, the mouse exhibited abundant gene expressions for Cyp3a25, Cyp4v3, Cyp2d26, followed by Cyp2b20, Cyp2c65 and Cyp4f14, whereas, the rat showed higher expression profiles of Cyp3a9, Cyp2b19, Cyp4f1, Cyp17a1, Cyp2d18, Cyp27a1 and Cyp4f6. However, the highly expressed P450 enzymes were CYP3A4, CYP3A5, CYP4F3, CYP2C18, CYP2C9, CYP2D6, CYP3A7, CYP11B1 and CYP2B6 in the human. For phase II enzymes, glucuronosyltransferase Ugt1a6, glutathione S-transferases Gstp1, Gstm3 and Gsta2, sulfotransferase Sult1b1 and acyltransferase Dgat1 were highly expressed in the mouse. The rat revealed predominant expression of glucuronosyltransferases Ugt1a1 and Ugt1a7, sulfotransferase Sult1b1, acetyltransferase Dlat and acyltransferase Dgat1. On the other hand, in human, glucuronosyltransferases UGT2B15 and UGT2B17, glutathione S-transferases MGST3, GSTP1, GSTA2 and GSTM4, sulfotransferases ST1A3 and SULT1A2, acetyltransferases SAT1 and CRAT, and acyltransferase AGPAT2 were dominantly detected. Therefore, current data indicated substantial interspecies differences in the pattern of intestinal gene expression both for P450 enzymes and phase II drug-metabolizing enzymes. This genomic database is expected to improve our understanding of interspecies variations in estimating intestinal prehepatic clearance of oral drugs.

  5. Functional annotation of rheumatoid arthritis and osteoarthritis associated genes by integrative genome-wide gene expression profiling analysis.

    Directory of Open Access Journals (Sweden)

    Zhan-Chun Li

    Full Text Available BACKGROUND: Rheumatoid arthritis (RA and osteoarthritis (OA are two major types of joint diseases that share multiple common symptoms. However, their pathological mechanism remains largely unknown. The aim of our study is to identify RA and OA related-genes and gain an insight into the underlying genetic basis of these diseases. METHODS: We collected 11 whole genome-wide expression profiling datasets from RA and OA cohorts and performed a meta-analysis to comprehensively investigate their expression signatures. This method can avoid some pitfalls of single dataset analyses. RESULTS AND CONCLUSION: We found that several biological pathways (i.e., the immunity, inflammation and apoptosis related pathways are commonly involved in the development of both RA and OA. Whereas several other pathways (i.e., vasopressin-related pathway, regulation of autophagy, endocytosis, calcium transport and endoplasmic reticulum stress related pathways present significant difference between RA and OA. This study provides novel insights into the molecular mechanisms underlying this disease, thereby aiding the diagnosis and treatment of the disease.

  6. Structure and expression of thyroglobulin gene

    Energy Technology Data Exchange (ETDEWEB)

    Vassart, G; Brocas, H; Christophe, D; de Martynoff, G; Leriche, A; Mercken, L; Pohl, V; van Heuverswyn, B [Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucleaire (IRIBHN), Faculte de Medecine, Universite libre de Bruxelles, Campus Hopital Erasme, Brussels (Belgium)

    1982-01-01

    Thyroglobulin is composed of two 300000 dalton polypeptide chains, translated from an 8000 base mRNA. Preparation of a full length cDNA and its cloning in E. coli have lead to the demonstration that the polypeptides of thyroglobulin protomers were identical. Used as molecular probes, the cloned cDNA allowed the isolation of a fragment of thyroglobulin gene. Electron microscopic studies have demonstrated that this gene contains more than 90 % intronic material separating small size exons (<200 bp). Sequencing of bovine thyroglobulin structural gene is in progress. Preliminary results show evidence for the existence of repetitive segments. Availability of cloned DNA complementary to bovine and human thyroglobulin mRNA allows the study of genetic defects of thyroglobulin gene expression in the human and in various animal models.

  7. Cerebrovascular gene expression in spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Frederiksen, Simona Denise; Edvinsson, Lars

    2017-01-01

    Hypertension is a hemodynamic disorder and one of the most important and well-established risk factors for vascular diseases such as stroke. Blood vessels exposed to chronic shear stress develop structural changes and remodeling of the vascular wall through many complex mechanisms. However......, the molecular mechanisms involved are not fully understood. Hypertension-susceptible genes may provide a novel insight into potential molecular mechanisms of hypertension and secondary complications associated with hypertension. The aim of this exploratory study was to identify gene expression differences......, the identified genes in the middle cerebral arteries from spontaneously hypertensive rats could be possible mediators of the vascular changes and secondary complications associated with hypertension. This study supports the selection of key genes to investigate in the future research of hypertension-induced end...

  8. Digital gene expression analysis of gene expression differences within Brassica diploids and allopolyploids.

    Science.gov (United States)

    Jiang, Jinjin; Wang, Yue; Zhu, Bao; Fang, Tingting; Fang, Yujie; Wang, Youping

    2015-01-27

    Brassica includes many successfully cultivated crop species of polyploid origin, either by ancestral genome triplication or by hybridization between two diploid progenitors, displaying complex repetitive sequences and transposons. The U's triangle, which consists of three diploids and three amphidiploids, is optimal for the analysis of complicated genomes after polyploidization. Next-generation sequencing enables the transcriptome profiling of polyploids on a global scale. We examined the gene expression patterns of three diploids (Brassica rapa, B. nigra, and B. oleracea) and three amphidiploids (B. napus, B. juncea, and B. carinata) via digital gene expression analysis. In total, the libraries generated between 5.7 and 6.1 million raw reads, and the clean tags of each library were mapped to 18547-21995 genes of B. rapa genome. The unambiguous tag-mapped genes in the libraries were compared. Moreover, the majority of differentially expressed genes (DEGs) were explored among diploids as well as between diploids and amphidiploids. Gene ontological analysis was performed to functionally categorize these DEGs into different classes. The Kyoto Encyclopedia of Genes and Genomes analysis was performed to assign these DEGs into approximately 120 pathways, among which the metabolic pathway, biosynthesis of secondary metabolites, and peroxisomal pathway were enriched. The non-additive genes in Brassica amphidiploids were analyzed, and the results indicated that orthologous genes in polyploids are frequently expressed in a non-additive pattern. Methyltransferase genes showed differential expression pattern in Brassica species. Our results provided an understanding of the transcriptome complexity of natural Brassica species. The gene expression changes in diploids and allopolyploids may help elucidate the morphological and physiological differences among Brassica species.

  9. Global gene expression in Escherichia coli biofilms

    DEFF Research Database (Denmark)

    Schembri, Mark; Kjærgaard, K.; Klemm, Per

    2003-01-01

    It is now apparent that microorganisms undergo significant changes during the transition from planktonic to biofilm growth. These changes result in phenotypic adaptations that allow the formation of highly organized and structured sessile communities, which possess enhanced resistance to antimicr......It is now apparent that microorganisms undergo significant changes during the transition from planktonic to biofilm growth. These changes result in phenotypic adaptations that allow the formation of highly organized and structured sessile communities, which possess enhanced resistance...... the transition to biofilm growth, and these included genes expressed under oxygen-limiting conditions, genes encoding (putative) transport proteins, putative oxidoreductases and genes associated with enhanced heavy metal resistance. Of particular interest was the observation that many of the genes altered...... in expression have no current defined function. These genes, as well as those induced by stresses relevant to biofilm growth such as oxygen and nutrient limitation, may be important factors that trigger enhanced resistance mechanisms of sessile communities to antibiotics and hydrodynamic shear forces....

  10. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    model to investigate the role of telomerase in AML, we were able to translate the observed effect into human AML patients and identify specific genes involved, which also predict survival patterns in AML patients. During these studies we have applied methods for investigating differentially expressed......-based gene-lookup webservices, called HemaExplorer and BloodSpot. These web-services support the aim of making data and analysis of haematopoietic cells from mouse and human accessible for researchers without bioinformatics expertise. Finally, in order to aid the analysis of the very limited number...

  11. Gene expression in Pseudomonas aeruginosa swarming motility

    Directory of Open Access Journals (Sweden)

    Déziel Eric

    2010-10-01

    Full Text Available Abstract Background The bacterium Pseudomonas aeruginosa is capable of three types of motilities: swimming, twitching and swarming. The latter is characterized by a fast and coordinated group movement over a semi-solid surface resulting from intercellular interactions and morphological differentiation. A striking feature of swarming motility is the complex fractal-like patterns displayed by migrating bacteria while they move away from their inoculation point. This type of group behaviour is still poorly understood and its characterization provides important information on bacterial structured communities such as biofilms. Using GeneChip® Affymetrix microarrays, we obtained the transcriptomic profiles of both bacterial populations located at the tip of migrating tendrils and swarm center of swarming colonies and compared these profiles to that of a bacterial control population grown on the same media but solidified to not allow swarming motility. Results Microarray raw data were corrected for background noise with the RMA algorithm and quantile normalized. Differentially expressed genes between the three conditions were selected using a threshold of 1.5 log2-fold, which gave a total of 378 selected genes (6.3% of the predicted open reading frames of strain PA14. Major shifts in gene expression patterns are observed in each growth conditions, highlighting the presence of distinct bacterial subpopulations within a swarming colony (tendril tips vs. swarm center. Unexpectedly, microarrays expression data reveal that a minority of genes are up-regulated in tendril tip populations. Among them, we found energy metabolism, ribosomal protein and transport of small molecules related genes. On the other hand, many well-known virulence factors genes were globally repressed in tendril tip cells. Swarm center cells are distinct and appear to be under oxidative and copper stress responses. Conclusions Results reported in this study show that, as opposed to

  12. A non-parametric meta-analysis approach for combining independent microarray datasets: application using two microarray datasets pertaining to chronic allograft nephropathy

    Directory of Open Access Journals (Sweden)

    Archer Kellie J

    2008-02-01

    Full Text Available Abstract Background With the popularity of DNA microarray technology, multiple groups of researchers have studied the gene expression of similar biological conditions. Different methods have been developed to integrate the results from various microarray studies, though most of them rely on distributional assumptions, such as the t-statistic based, mixed-effects model, or Bayesian model methods. However, often the sample size for each individual microarray experiment is small. Therefore, in this paper we present a non-parametric meta-analysis approach for combining data from independent microarray studies, and illustrate its application on two independent Affymetrix GeneChip studies that compared the gene expression of biopsies from kidney transplant recipients with chronic allograft nephropathy (CAN to those with normal functioning allograft. Results The simulation study comparing the non-parametric meta-analysis approach to a commonly used t-statistic based approach shows that the non-parametric approach has better sensitivity and specificity. For the application on the two CAN studies, we identified 309 distinct genes that expressed differently in CAN. By applying Fisher's exact test to identify enriched KEGG pathways among those genes called differentially expressed, we found 6 KEGG pathways to be over-represented among the identified genes. We used the expression measurements of the identified genes as predictors to predict the class labels for 6 additional biopsy samples, and the predicted results all conformed to their pathologist diagnosed class labels. Conclusion We present a new approach for combining data from multiple independent microarray studies. This approach is non-parametric and does not rely on any distributional assumptions. The rationale behind the approach is logically intuitive and can be easily understood by researchers not having advanced training in statistics. Some of the identified genes and pathways have been

  13. Decomposition of gene expression state space trajectories.

    Directory of Open Access Journals (Sweden)

    Jessica C Mar

    2009-12-01

    Full Text Available Representing and analyzing complex networks remains a roadblock to creating dynamic network models of biological processes and pathways. The study of cell fate transitions can reveal much about the transcriptional regulatory programs that underlie these phenotypic changes and give rise to the coordinated patterns in expression changes that we observe. The application of gene expression state space trajectories to capture cell fate transitions at the genome-wide level is one approach currently used in the literature. In this paper, we analyze the gene expression dataset of Huang et al. (2005 which follows the differentiation of promyelocytes into neutrophil-like cells in the presence of inducers dimethyl sulfoxide and all-trans retinoic acid. Huang et al. (2005 build on the work of Kauffman (2004 who raised the attractor hypothesis, stating that cells exist in an expression landscape and their expression trajectories converge towards attractive sites in this landscape. We propose an alternative interpretation that explains this convergent behavior by recognizing that there are two types of processes participating in these cell fate transitions-core processes that include the specific differentiation pathways of promyelocytes to neutrophils, and transient processes that capture those pathways and responses specific to the inducer. Using functional enrichment analyses, specific biological examples and an analysis of the trajectories and their core and transient components we provide a validation of our hypothesis using the Huang et al. (2005 dataset.

  14. Mass meta-analysis in Talairach space

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup

    2004-01-01

    We provide a method for mass meta-analysis in a neuroinformatics database containing stereotaxic Talairach coordinates from neuroimaging experiments. Database labels are used to group the individual experiments, e.g., according to cognitive function, and the consistent pattern of the experiments...... of experiments, and the distances to the null hypotheses are used to sort the voxels across groups of experiments. This allows for mass meta-analysis, with the construction of a list with the most prominent associations between brain areas and group labels. Furthermore, the method can be used for functional...

  15. Cross-platform analysis of cancer microarray data improves gene expression based classification of phenotypes

    Directory of Open Access Journals (Sweden)

    Eils Roland

    2005-11-01

    Full Text Available Abstract Background The extensive use of DNA microarray technology in the characterization of the cell transcriptome is leading to an ever increasing amount of microarray data from cancer studies. Although similar questions for the same type of cancer are addressed in these different studies, a comparative analysis of their results is hampered by the use of heterogeneous microarray platforms and analysis methods. Results In contrast to a meta-analysis approach where results of different studies are combined on an interpretative level, we investigate here how to directly integrate raw microarray data from different studies for the purpose of supervised classification analysis. We use median rank scores and quantile discretization to derive numerically comparable measures of gene expression from different platforms. These transformed data are then used for training of classifiers based on support vector machines. We apply this approach to six publicly available cancer microarray gene expression data sets, which consist of three pairs of studies, each examining the same type of cancer, i.e. breast cancer, prostate cancer or acute myeloid leukemia. For each pair, one study was performed by means of cDNA microarrays and the other by means of oligonucleotide microarrays. In each pair, high classification accuracies (> 85% were achieved with training and testing on data instances randomly chosen from both data sets in a cross-validation analysis. To exemplify the potential of this cross-platform classification analysis, we use two leukemia microarray data sets to show that important genes with regard to the biology of leukemia are selected in an integrated analysis, which are missed in either single-set analysis. Conclusion Cross-platform classification of multiple cancer microarray data sets yields discriminative gene expression signatures that are found and validated on a large number of microarray samples, generated by different laboratories and

  16. Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

    KAUST Repository

    Horiuchi, Youko; Harushima, Yoshiaki; Fujisawa, Hironori; Mochizuki, Takako; Fujita, Masahiro; Ohyanagi, Hajime; Kurata, Nori

    2015-01-01

    Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue

  17. Blood Gene Expression Predicts Bronchiolitis Obliterans Syndrome

    Directory of Open Access Journals (Sweden)

    Richard Danger

    2018-01-01

    Full Text Available Bronchiolitis obliterans syndrome (BOS, the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group, and 26 samples at or after BOS diagnosis (diagnosis group. An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group. We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1, T-cell leukemia/lymphoma protein 1A (TCL1A, and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p < 0.01 and are not associated with time posttransplantation. This is the first published large-scale gene expression analysis of blood after lung transplantation. The three-gene blood signature could provide clinicians with new tools to improve follow-up and adapt treatment of patients likely to develop BOS.

  18. Genetic susceptibility to bone and soft tissue sarcomas: a field synopsis and meta-analysis.

    Science.gov (United States)

    Benna, Clara; Simioni, Andrea; Pasquali, Sandro; De Boni, Davide; Rajendran, Senthilkumar; Spiro, Giovanna; Colombo, Chiara; Virgone, Calogero; DuBois, Steven G; Gronchi, Alessandro; Rossi, Carlo Riccardo; Mocellin, Simone

    2018-04-06

    The genetic architecture of bone and soft tissue sarcomas susceptibility is yet to be elucidated. We aimed to comprehensively collect and meta-analyze the current knowledge on genetic susceptibility in these rare tumors. We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing sarcomas through searching PubMed, The Cochrane Library, Scopus and Web of Science databases. To evaluate result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Integrative analysis of genetic and eQTL (expression quantitative trait locus) data was coupled with network and pathway analysis to explore the hypothesis that specific cell functions are involved in sarcoma predisposition. We retrieved 90 eligible studies comprising 47,796 subjects (cases: 14,358, 30%) and investigating 1,126 polymorphisms involving 320 distinct genes. Meta-analysis identified 55 single nucleotide polymorphisms (SNPs) significantly associated with disease risk with a high (N=9), moderate (N=38) and low (N=8) level of evidence, findings being classified as noteworthy basically only when the level of evidence was high. The estimated joint population attributable risk for three independent SNPs (rs11599754 of ZNF365/EGR2 , rs231775 of CTLA4 , and rs454006 of PRKCG ) was 37.2%. We also identified 53 SNPs significantly associated with sarcoma risk based on single studies.Pathway analysis enabled us to propose that sarcoma predisposition might be linked especially to germline variation of genes whose products are involved in the function of the DNA repair machinery. We built the first knowledgebase on the evidence linking DNA variation to sarcomas susceptibility, which can be used to generate mechanistic hypotheses and inform future studies in this field of oncology.

  19. Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

    International Nuclear Information System (INIS)

    Salem, Tamer Z.; Zhang, Fengrui; Thiem, Suzanne M.

    2013-01-01

    Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

  20. Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Salem, Tamer Z. [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbial Molecular Biology, AGERI, Agricultural Research Center, Giza 12619 (Egypt); Division of Biomedical Sciences, Zewail University, Zewail City of Science and Technology, Giza 12588 (Egypt); Zhang, Fengrui [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Thiem, Suzanne M., E-mail: smthiem@msu.edu [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States)

    2013-01-20

    Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

  1. Three gene expression vector sets for concurrently expressing multiple genes in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ishii, Jun; Kondo, Takashi; Makino, Harumi; Ogura, Akira; Matsuda, Fumio; Kondo, Akihiko

    2014-05-01

    Yeast has the potential to be used in bulk-scale fermentative production of fuels and chemicals due to its tolerance for low pH and robustness for autolysis. However, expression of multiple external genes in one host yeast strain is considerably labor-intensive due to the lack of polycistronic transcription. To promote the metabolic engineering of yeast, we generated systematic and convenient genetic engineering tools to express multiple genes in Saccharomyces cerevisiae. We constructed a series of multi-copy and integration vector sets for concurrently expressing two or three genes in S. cerevisiae by embedding three classical promoters. The comparative expression capabilities of the constructed vectors were monitored with green fluorescent protein, and the concurrent expression of genes was monitored with three different fluorescent proteins. Our multiple gene expression tool will be helpful to the advanced construction of genetically engineered yeast strains in a variety of research fields other than metabolic engineering. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  2. Dyadic Interracial Interactions: A Meta-Analysis

    Science.gov (United States)

    Toosi, Negin R.; Babbitt, Laura G.; Ambady, Nalini; Sommers, Samuel R.

    2012-01-01

    This meta-analysis examined over 40 years of research on interracial interactions by exploring 4 types of outcomes: explicit attitudes toward interaction partners, participants' self-reports of their own emotional state, nonverbal or observed behavior, and objective measures of performance. Data were collected from 108 samples (N = 12,463)…

  3. Meta-analysis in clinical trials revisited.

    Science.gov (United States)

    DerSimonian, Rebecca; Laird, Nan

    2015-11-01

    In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effects model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the "DerSimonian and Laird method" is now often referred to as the 'standard approach' or a 'popular' method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. Published by Elsevier Inc.

  4. A Bayesian Nonparametric Meta-Analysis Model

    Science.gov (United States)

    Karabatsos, George; Talbott, Elizabeth; Walker, Stephen G.

    2015-01-01

    In a meta-analysis, it is important to specify a model that adequately describes the effect-size distribution of the underlying population of studies. The conventional normal fixed-effect and normal random-effects models assume a normal effect-size population distribution, conditionally on parameters and covariates. For estimating the mean overall…

  5. Wind power externalities: A meta-analysis

    NARCIS (Netherlands)

    Mattmann, M.; Logar, I.; Brouwer, R.

    2016-01-01

    This study presents the first quantitative meta-analysis of the non-market valuation literature on the external effects associated with wind power production. A data set of 60 observations drawn from 32 studies is constructed. The relative economic values of different types of externalities as well

  6. Meta-Analysis of Coefficient Alpha

    Science.gov (United States)

    Rodriguez, Michael C.; Maeda, Yukiko

    2006-01-01

    The meta-analysis of coefficient alpha across many studies is becoming more common in psychology by a methodology labeled reliability generalization. Existing reliability generalization studies have not used the sampling distribution of coefficient alpha for precision weighting and other common meta-analytic procedures. A framework is provided for…

  7. Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

    Science.gov (United States)

    Li, Yun R; Li, Jin; Zhao, Sihai D; Bradfield, Jonathan P; Mentch, Frank D; Maggadottir, S Melkorka; Hou, Cuiping; Abrams, Debra J; Chang, Diana; Gao, Feng; Guo, Yiran; Wei, Zhi; Connolly, John J; Cardinale, Christopher J; Bakay, Marina; Glessner, Joseph T; Li, Dong; Kao, Charlly; Thomas, Kelly A; Qiu, Haijun; Chiavacci, Rosetta M; Kim, Cecilia E; Wang, Fengxiang; Snyder, James; Richie, Marylyn D; Flatø, Berit; Førre, Øystein; Denson, Lee A; Thompson, Susan D; Becker, Mara L; Guthery, Stephen L; Latiano, Anna; Perez, Elena; Resnick, Elena; Russell, Richard K; Wilson, David C; Silverberg, Mark S; Annese, Vito; Lie, Benedicte A; Punaro, Marilynn; Dubinsky, Marla C; Monos, Dimitri S; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Kugathasan, Subra; Ellis, Justine A; Munro, Jane E; Sullivan, Kathleen E; Wise, Carol A; Chapel, Helen; Cunningham-Rundles, Charlotte; Grant, Struan F A; Orange, Jordan S; Sleiman, Patrick M A; Behrens, Edward M; Griffiths, Anne M; Satsangi, Jack; Finkel, Terri H; Keinan, Alon; Prak, Eline T Luning; Polychronakos, Constantin; Baldassano, Robert N; Li, Hongzhe; Keating, Brendan J; Hakonarson, Hakon

    2016-01-01

    Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ2 meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico–replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases. PMID:26301688

  8. Gene Expression Profiling of Xeroderma Pigmentosum

    Directory of Open Access Journals (Sweden)

    Bowden Nikola A

    2006-05-01

    Full Text Available Abstract Xeroderma pigmentosum (XP is a rare recessive disorder that is characterized by extreme sensitivity to UV light. UV light exposure results in the formation of DNA damage such as cyclobutane dimers and (6-4 photoproducts. Nucleotide excision repair (NER orchestrates the removal of cyclobutane dimers and (6-4 photoproducts as well as some forms of bulky chemical DNA adducts. The disease XP is comprised of 7 complementation groups (XP-A to XP-G, which represent functional deficiencies in seven different genes, all of which are believed to be involved in NER. The main clinical feature of XP is various forms of skin cancers; however, neurological degeneration is present in XPA, XPB, XPD and XPG complementation groups. The relationship between NER and other types of DNA repair processes is now becoming evident but the exact relationships between the different complementation groups remains to be precisely determined. Using gene expression analysis we have identified similarities and differences after UV light exposure between the complementation groups XP-A, XP-C, XP-D, XP-E, XP-F, XP-G and an unaffected control. The results reveal that there is a graded change in gene expression patterns between the mildest, most similar to the control response (XP-E and the severest form (XP-A of the disease, with the exception of XP-D. Distinct differences between the complementation groups with neurological symptoms (XP-A, XP-D and XP-G and without (XP-C, XP-E and XP-F were also identified. Therefore, this analysis has revealed distinct gene expression profiles for the XP complementation groups and the first step towards understanding the neurological symptoms of XP.

  9. Association of ESRα Gene Pvu II T>C, XbaI A>G and BtgI G>A Polymorphisms with Knee Osteoarthritis Susceptibility: A Systematic Review and Meta-Analysis Based on 22 Case-Control Studies

    Directory of Open Access Journals (Sweden)

    Masoud Mehdinejad Yazdi

    2017-11-01

    Full Text Available Background: Many studies have reported the association of estrogen receptor α gene (ESRα ESRα PvuII T>C, XbaI A>G and BtgI G>A polymorphisms with Knee osteoarthritis (KOA risk, but the results remained controversial. In order to drive a more precise estimation, the present systematic review and meta-analysis was performed to investigate the association between ESRα polymorphisms and KOA susceptibility. Methods: Eligible articles were identified by search of databases including PubMed, ISI Web of Knowledge and Google scholar up to March 1, 2017. Data were extracted by two independent authors and pooled odds ratio (OR with 95% confidence interval (CI was calculated. Results: A total of 22 case-control studies in eleven publications with 6,575 KOA cases and 7,459 controls were included in the m