Title | A phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Pendergrass 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 Authors | Crawford DC |
Journal | PLoS One |
Volume | 14 |
Issue | 12 |
Pagination | e0226771 |
Date Published | 2019 |
ISSN | 1932-6203 |
Keywords | African 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 |
DOI | 10.1371/journal.pone.0226771 |
Alternate Journal | PLoS One |
PubMed ID | 31891604 |
PubMed Central ID | PMC6938343 |
Grant List | UL1 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 |