Citation
Pendergrass, Sarah A.; Brown-Gentry, Kristin; Dudek, Scott M.; Frase, Alex T.; Torstenson, Eric S.; Goodloe, Robert; Ambite, Jose Luis; Avery, Christy L.; Buyske, Steven G.; & Buzkova, Petra, et al. (2013). Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture Using Genomics and Epidemiology (PAGE) Network. PLOS Genetics, 9(1), e1003087. PMCID: PMC3561060Abstract
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, forURL
http://dx.doi.org/10.1371/journal.pgen.1003087Reference Type
Journal ArticleYear Published
2013Journal Title
PLOS GeneticsAuthor(s)
Pendergrass, Sarah A.Brown-Gentry, Kristin
Dudek, Scott M.
Frase, Alex T.
Torstenson, Eric S.
Goodloe, Robert
Ambite, Jose Luis
Avery, Christy L.
Buyske, Steven G.
Buzkova, Petra
Deelman, Ewa
Fesinmeyer, Megan D.
Haiman, Christopher A.
Heiss, Gerardo M.
Hindorff, Lucia A.
Hsu, Chu-Nan
Jackson, Rebecca D.
Kooperberg, Charles L.
Le Marchand, Loic
Lin, Yi
Matise, Tara C.
Monroe, Kristine R.
Moreland, Larry
Park, Sung-Shim L.
Reiner, Alexander P.
Wallace, Robert
Wilkens, Lynne R.
Crawford, Dana C.
Ritchie, Marylyn D.