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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Franceschini, N; Fox, E; Zhang, Z; Edwards, TL; Nalls, MA; Sung, YJ; Tayo, BO; Sun, YV; Gottesman, O; Adeyemo, A; Johnson, AD; Young, JH; Rice, K; Duan, Q; Chen, F; Li, Y; Tang, H; Fornage, M; Keene, KL; Andrews, JS; Smith, JA; Faul, JD; Guangfa, Z; Guo, W; Liu, Y; Murray, SS; Musani, SK; Srinivasan, S; Velez Edwards, DR; Wang, H; Becker, LC; Bovet, P; Bochud, M; Broeckel, U; Burnier, M; Carty, C; Chasman, DI; Ehret, G; Chen, W-M; Chen, G; Chen, W; Ding, J; Dreisbach, AW; Evans, MK; Guo, X; Garcia, ME; Jensen, R; Keller, MF; Lettre, G; Lotay, V; Martin, LW; Moore, JH; Morrison, AC; Mosley, TH; Ogunniyi, A; Palmas, W; Papanicolaou, G; Penman, A; Polak, JF; Ridker, PM; Salako, B; Singleton, AB; Shriner, D; Taylor, KD; Vasan, R; Wiggins, K; Williams, SM; Yanek, LR; Zhao, W; Zonderman, AB; Becker, DM; Berenson, G; Boerwinkle, E; Bottinger, E; Cushman, M; Eaton, C; Nyberg, F; Heiss, G; Hirschhron, JN; Howard, VJ; Karczewsk, KJ; Lanktree, MB; Liu, K; Liu, Y; Loos, R; Margolis, K; Snyder, M; Asian Genetic Epidemiology Network Consortium, ; Psaty, BM; Schork, NJ; Weir, DR; Rotimi, CN; Sale, MM; Harris, T; Kardia, SLR; Hunt, SC; Arnett, D; Redline, S; Cooper, RS; Risch, NJ; Rao, DC; Rotter, JI; Chakravarti, A; Reiner, AP; Levy, D; Keating, BJ; Zhu, X

Published Date

  • September 5, 2013

Published In

Volume / Issue

  • 93 / 3

Start / End Page

  • 545 - 554

PubMed ID

  • 23972371

Pubmed Central ID

  • PMC3769920

Electronic International Standard Serial Number (EISSN)

  • 1537-6605

Digital Object Identifier (DOI)

  • 10.1016/j.ajhg.2013.07.010

Language

  • eng

Conference Location

  • United States