Genome-wide association analysis of blood-pressure traits in african-ancestry individuals reveals common associated genes in African and Non-African populations

Nora Franceschini, The University of North Carolina at Chapel Hill
Ervin Fox, University of Mississippi Medical Center
Zhaogong Zhang, Case Western Reserve University
Todd L. Edwards, Vanderbilt University Medical Center
Michael A. Nalls, National Institute on Aging (NIA)
Yun Ju Sung, Washington University School of Medicine in St. Louis
Bamidele O. Tayo, Loyola University Stritch School of Medicine
Yan V. Sun, Rollins School of Public Health
Omri Gottesman, Icahn School of Medicine at Mount Sinai
Adebawole Adeyemo, National Human Genome Research Institute (NHGRI)
Andrew D. Johnson, Center for Population Studies, National Heart, Lung, and Blood Institute
J. Hunter Young, Johns Hopkins School of Medicine
Ken Rice, University of Washington, Seattle
Qing Duan, The University of North Carolina at Chapel Hill
Fang Chen, University of Virginia School of Medicine
Yun Li, The University of North Carolina at Chapel Hill
Hua Tang, Stanford University School of Medicine
Myriam Fornage, University of Texas School of Public Health
Keith L. Keene, University of Virginia School of Medicine
Jeanette S. Andrews, Wake Forest School of Medicine
Jennifer A. Smith, University of Michigan, Ann Arbor
Jessica D. Faul, University of Michigan, Ann Arbor
Zhang Guangfa, Scripps Research Institute
Wei Guo, Case Western Reserve University
Yu Liu, CASE School of Medicine
Sarah S. Murray, Tulane Center for Cardiovascular Health
Solomon K. Musani, University of Mississippi Medical Center
Sathanur Srinivasan, Tulane Center for Cardiovascular Health
Digna R. Velez Edwards, Vanderbilt University Medical Center
Heming Wang, Case Western Reserve University
Lewis C. Becker, Johns Hopkins University
Pascal Bovet, Institut Universitaire de Médecine Sociale et Préventive Lausanne

Document Type

Journal Article

Publication Date

9-5-2013

Journal

American Journal of Human Genetics

Volume

93

Issue

3

DOI

10.1016/j.ajhg.2013.07.010

Abstract

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10-8) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability. © 2013 The American Society of Human Genetics.

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