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A phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans.

TitleA phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans.
Publication TypeJournal Article
Year of Publication2019
AuthorsPendergrass SA, Buyske S, Jeff JM, Frase A, Dudek S, Bradford Y, Ambite J-L, Avery CL, Bůžková P, Deelman E, Fesinmeyer MD, Haiman C, Heiss G, Hindorff LA, Hsu C-N, Jackson RD, Lin Y, Le Marchand L, Matise TC, Monroe KR, Moreland L, North KE, Park SL, Reiner A, Wallace R, Wilkens LR, Kooperberg C, Ritchie MD
Secondary AuthorsCrawford DC
JournalPLoS One
Volume14
Issue12
Paginatione0226771
Date Published2019
ISSN1932-6203
KeywordsAfrican Americans, Aged, Atherosclerosis, Epidemiologic Studies, Female, Genetic Pleiotropy, Genome-Wide Association Study, Humans, Male, Metagenomics, Middle Aged, Phenomics, Polymorphism, Single Nucleotide
Abstract

We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study. The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio-metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p

DOI10.1371/journal.pone.0226771
Alternate JournalPLoS One
PubMed ID31891604
PubMed Central IDPMC6938343
Grant ListUL1 TR000439 / TR / NCATS NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
UL1 TR002548 / TR / NCATS NIH HHS / United States
U01 HG004801 / HG / NHGRI NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
R37 CA054281 / CA / NCI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
N01 WH022110 / WH / WHI NIH HHS / United States
U01 CA136792 / CA / NCI NIH HHS / United States
P01 CA033619 / CA / NCI NIH HHS / United States
U01 HG004798 / HG / NHGRI NIH HHS / United States
N01HC55020 / HL / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
U01 HG004802 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
U01 CA098758 / CA / NCI NIH HHS / United States
P30 CA071789 / CA / NCI NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
U01 HG004803 / HG / NHGRI NIH HHS / United States