Journal article
A phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans
PloS one, Vol.14(12), pp.e0226771-e0226771
2019
DOI: 10.1371/journal.pone.0226771
PMCID: PMC6938343
PMID: 31891604
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<0.01 in two or more PAGE study sites for two or more phenotype classes. We further annotated these PheWAS-identified variants using publicly available functional data and local genetic ancestry. Amongst our novel findings is SPARC rs4958487, associated with increased glucose levels and hypertension. SPARC has been implicated in the pathogenesis of diabetes and is also known to have a potential role in fibrosis, a common consequence of multiple conditions including hypertension. The SPARC example and others highlight the potential that PheWAS approaches have in improving our understanding of complex disease architecture by identifying novel relationships between genetic variants and an array of common human phenotypes.
Details
- Title: Subtitle
- A phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans
- Creators
- Sarah A Pendergrass - GenentechSteven Buyske - Rutgers, The State University of New JerseyJanina M Jeff - Illumina (United States)Alex Frase - University of PennsylvaniaScott Dudek - University of PennsylvaniaYuki Bradford - University of PennsylvaniaJose-Luis Ambite - Information Sciences InstituteChristy L Avery - University of North Carolina at Chapel HillPetra Buzkova - University of WashingtonEwa Deelman - Information Sciences InstituteMegan D Fesinmeyer - Amgen (Australia)Christopher Haiman - University of Southern CaliforniaGerardo Heiss - University of North Carolina at Chapel HillLucia A Hindorff - National Human Genome Research InstituteChun-Nan Hsu - University of California San DiegoRebecca D Jackson - The Ohio State UniversityYi Lin - Fred Hutch Cancer CenterLoic Le Marchand - University of Hawaii SystemTara C Matise - Rutgers, The State University of New JerseyKristine R Monroe - University of Southern CaliforniaLarry Moreland - University of PittsburghKari E North - University of North Carolina at Chapel HillSungshim L Park - University of Southern CaliforniaAlex Reiner - University of WashingtonRobert Wallace - University of IowaLynne R Wilkens - University of Hawaii SystemCharles Kooperberg - Fred Hutch Cancer CenterMarylyn D Ritchie - University of PennsylvaniaDana C Crawford - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.14(12), pp.e0226771-e0226771
- DOI
- 10.1371/journal.pone.0226771
- PMID
- 31891604
- PMCID
- PMC6938343
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Grant note
- N01HC55016 / NHLBI NIH HHS U01 HG004803 / NHGRI NIH HHS N01HC55018 / NHLBI NIH HHS P30 CA071789 / NCI NIH HHS U01 HG004798 / NHGRI NIH HHS U01 CA136792 / NCI NIH HHS N01 HC055018 / NHLBI NIH HHS P30 ES010126 / NIEHS NIH HHS N01HC55019 / NHLBI NIH HHS N01HC55021 / NHLBI NIH HHS N01 HC055015 / NHLBI NIH HHS U01 CA098758 / NCI NIH HHS U01 HG004802 / NHGRI NIH HHS N01 HC055019 / NHLBI NIH HHS N01HC55015 / NHLBI NIH HHS N01HC55020 / NHLBI NIH HHS R37 CA054281 / NCI NIH HHS N01HC55022 / NHLBI NIH HHS N01 WH022110 / WHI NIH HHS UL1 TR000439 / NCATS NIH HHS U01 HG004790 / NHGRI NIH HHS N01WH22110 / WHI NIH HHS UL1 TR002548 / NCATS NIH HHS P01 CA033619 / NCI NIH HHS U01 HG004801 / NHGRI NIH HHS
- Language
- English
- Date published
- 2019
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984364423002771
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