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

TitleGenome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.
Publication TypeJournal Article
Year of Publication2013
AuthorsFranceschini, N, Fox, E, Zhang, Z, Edwards, TL, Nalls, MA, Sung, YJu, Tayo, BO, Sun, YV, Gottesman, O, Adeyemo, A, Johnson, AD, J Young, H, Rice, K, Duan, Q, Chen, F, Li, Y, Tang, H, Fornage, M, Keene, KL, Andrews, JS, Smith, JA, Faul, J, Guangfa, Z, Guo, W, Liu, Y, Murray, SS, Musani, SK, Srinivasan, S, Edwards, DRVelez, Wang, H, Becker, LC, Bovet, P, Bochud, M, Broeckel, U, Burnier, M, Carty, C, Chasman, DI, Ehret, GB, 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, WR, Papanicolaou, GJ, Penman, A, Polak, JF, Ridker, PM, Salako, B, Singleton, AB, Shriner, D, Taylor, KD, Vasan, RS, Wiggins, K, Williams, SM, Yanek, LR, Zhao, W, Zonderman, AB, Becker, DM, Berenson, G, Boerwinkle, E, Bottinger, EP, Cushman, M, Eaton, CB, Nyberg, F, Heiss, G, Hirschhron, JN, Howard, VJ, Karczewsk, KJ, Lanktree, MB, Liu, K, Liu, Y, Loos, RJF, Margolis, K, Snyder, M, Psaty, BM, Schork, NJ, Weir, DR, Rotimi, CN, Sale, MM, Harris, TB, Kardia, SLR, Hunt, SC, Arnett, DK, Redline, S, Cooper, RS, Risch, N, Rao, DC, Rotter, JI, Chakravarti, A, Reiner, AP, Levy, D, Keating, BJ, Zhu, X
Corporate AuthorsAsian Genetic Epidemiology Network Consortium
JournalAm J Hum Genet
Date Published2013 Sep 05
ISSN Number1537-6605
KeywordsAfrica, African Continental Ancestry Group, Blood pressure, Cohort Studies, Databases, Genetic, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Reproducibility of Results

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.

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Alternate JournalAm. J. Hum. Genet.
Citation Key8608
PubMed ID23972371
PubMed Central IDPMC3769920
Grant ListP20 GM103534 / GM / NIGMS NIH HHS / United States
R01 HG003054 / HG / NHGRI NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
P20 MD006899 / MD / NIMHD NIH HHS / United States
R01 HL055673 / HL / NHLBI NIH HHS / United States