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Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network
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نویسنده
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pendergrass s.a. ,brown-gentry k. ,dudek s. ,frase a. ,torstenson e.s. ,goodloe r. ,ambite j.l. ,avery c.l. ,buyske s. ,bůžková p. ,deelman e. ,fesinmeyer m.d. ,haiman c.a. ,heiss g. ,hindorff l.a. ,hsu c.-n. ,jackson r.d. ,kooperberg c. ,le marchand l. ,lin y. ,matise t.c. ,monroe k.r. ,moreland l. ,park s.l. ,reiner a. ,wallace r. ,wilkens l.r. ,crawford d.c. ,ritchie m.d.
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منبع
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plos genetics - 2013 - دوره : 9 - شماره : 1
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چکیده
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Using a phenome-wide association study (phewas) approach,we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the population architecture using genomics and epidemiology (page) network. our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. this phewas drew on five population-based studies representing four major racial/ethnic groups (european americans (ea),african americans (aa),hispanics/mexican-americans,and asian/pacific islanders) in page,each site with measurements for multiple traits,associated laboratory measures,and intermediate biomarkers. a total of 83 single nucleotide polymorphisms (snps) identified by genome-wide association studies (gwas) were genotyped across two or more page study sites. comprehensive tests of association,stratified by race/ethnicity,were performed,encompassing 4,706 phenotypes mapped to 105 phenotype-classes,and association results were compared across study sites. a total of 111 phewas results had significant associations for two or more page study sites with consistent direction of effect with a significance threshold of p<0.01 for the same racial/ethnic group,snp,and phenotype-class. among results identified for snps previously associated with phenotypes such as lipid traits,type 2 diabetes,and body mass index,52 replicated previously published genotype-phenotype associations,26 represented phenotypes closely related to previously known genotype-phenotype associations,and 33 represented potentially novel genotype-phenotype associations with pleiotropic effects. the majority of the potentially novel results were for single phewas phenotype-classes,for example,for cdkn2a/b rs1333049 (previously associated with type 2 diabetes in ea) a phewas association was identified for hemoglobin levels in aa. of note,however,galnt2 rs2144300 (previously associated with high-density lipoprotein cholesterol levels in ea) had multiple potentially novel phewas associations,with hypertension related phenotypes in aa and with serum calcium levels and coronary artery disease phenotypes in ea. phewas identifies associations for hypothesis generation and exploration of the genetic architecture of complex traits.
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آدرس
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center for systems genomics,department of biochemistry and molecular biology,the pennsylvania state university,eberly college of science,the huck institutes of the life sciences,university park,pa, United States, center for human genetics research,vanderbilt university,nashville,tn, United States, center for human genetics research,vanderbilt university,nashville,tn, United States, center for systems genomics,department of biochemistry and molecular biology,the pennsylvania state university,eberly college of science,the huck institutes of the life sciences,university park,pa, United States, center for human genetics research,vanderbilt university,nashville,tn, United States, center for human genetics research,vanderbilt university,nashville,tn, United States, information sciences institute,university of southern california,marina del rey,ca, United States, department of epidemiology,university of north carolina,chapel hill,nc, United States, department of genetics,rutgers university,piscataway,nj,united states,department of statistics,rutgers university,piscataway,nj, United States, department of biostatistics,university of washington,seattle,wa, United States, information sciences institute,university of southern california,marina del rey,ca, United States, division of public health,fred hutchinson cancer research center,seattle,wa, United States, department of preventive medicine,keck school of medicine,university of southern california/norris comprehensive cancer center,los angeles,ca, United States, department of epidemiology,university of north carolina,chapel hill,nc, United States, national human genome research institute,national institutes of health,bethesda,md, United States, information sciences institute,university of southern california,marina del rey,ca, United States, ohio state university,columbus,oh, United States, division of public health,fred hutchinson cancer research center,seattle,wa, United States, epidemiology program,university of hawaii cancer center,honolulu,hi, United States, division of public health,fred hutchinson cancer research center,seattle,wa, United States, department of genetics,rutgers university,piscataway,nj, United States, department of preventive medicine,keck school of medicine,university of southern california/norris comprehensive cancer center,los angeles,ca, United States, university of pittsburgh,pittsburgh,pa, United States, epidemiology program,university of hawaii cancer center,honolulu,hi, United States, division of public health,fred hutchinson cancer research center,seattle,wa,united states,department of epidemiology,university of washington,seattle,wa, United States, departments of epidemiology and internal medicine,university of iowa,iowa city,ia, United States, epidemiology program,university of hawaii cancer center,honolulu,hi, United States, center for human genetics research,vanderbilt university,nashville,tn,united states,department of molecular physiology and biophysics,vanderbilt university,nashville,tn, United States, center for systems genomics,department of biochemistry and molecular biology,the pennsylvania state university,eberly college of science,the huck institutes of the life sciences,university park,pa, United States
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Authors
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