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

Nora Franceschini*, Ervin Fox, Zhaogong Zhang, Todd L. Edwards, Michael A. Nalls, Yun Ju Sung, Bamidele O. Tayo, Yan V. Sun, Omri Gottesman, Adebawole Adeyemo, Andrew D. Johnson, J. Hunter Young, Ken Rice, Qing Duan, Fang Chen, Yun Li, Hua Tang, Myriam Fornage, Keith L. Keene, Jeanette S. AndrewsJennifer A. Smith, Jessica D. Faul, Zhang Guangfa, Wei Guo, Yu Liu, Sarah S. Murray, Solomon K. Musani, Sathanur Srinivasan, Digna R. Velez Edwards, Heming Wang, Lewis C. Becker, Pascal Bovet, Murielle Bochud, Ulrich Broeckel, Michel Burnier, Cara Carty, Daniel I. Chasman, Georg Ehret, Wei Min Chen, Guanjie Chen, Wei Chan, Jingzhong Ding, Albert W. Dreisbach, Michele K. Evans, Xiuqing Guo, Melissa E. Garcia, Rich Jensen, Margaux F. Keller, Guillaume Lettre, Vaneet Lotay, Lisa W. Martin, Jason H. Moore, Alanna C. Morrison, Thomas H. Mosley, Adesola Ogunniyi, Walter Palmas, George Papanicolaou, Alan Penman, Joseph F. Polak, Paul M. Ridker, Babatunde Salako, Andrew B. Singleton, Daniel Shriner, Kent D. Taylor, Ramachandran Vasan, Kerri Wiggins, Scott M. Williams, Lisa R. Yanek, Wei Zhao, Alan B. Zonderman, Diane M. Becker, Gerald Berenson, Eric Boerwinkle, Erwin Bottinger, Mary Cushman, Charles Eaton, Fredrik Nyberg, Gerardo Heiss, Joel N. Hirschhron, Virginia J. Howard, Konrad J. Karczewsk, Matthew B. Lanktree, Kiang Liu, Yongmei Liu, Ruth Loos, Karen Margolis, Michael Snyder, Bruce M. Psaty, Nicholas J. Schork, David R. Weir, Charles N. Rotimi, Michele M. Sale, Tamara Harris, Sharon L.R. Kardia, Steven C. Hunt, Donna Arnett, Susan Redline, Richard S. Cooper, Neil J. Risch, D. C. Rao, Jerome I. Rotter, Aravinda Chakravarti, Alex P. Reiner, Daniel Levy, Brendan J. Keating, Xiaofeng Zhu

*Corresponding author for this work

Research output: Contribution to journalArticle

109 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)545-554
Number of pages10
JournalAmerican journal of human genetics
Volume93
Issue number3
DOIs
StatePublished - Sep 5 2013

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Franceschini, N., Fox, E., Zhang, Z., Edwards, T. L., Nalls, M. A., Sung, Y. J., Tayo, B. O., Sun, Y. V., Gottesman, O., Adeyemo, A., Johnson, A. D., Young, J. H., Rice, K., Duan, Q., Chen, F., Li, Y., Tang, H., Fornage, M., Keene, K. L., ... Zhu, X. (2013). Genome-wide association analysis of blood-pressure traits in african-ancestry individuals reveals common associated genes in African and Non-African populations. American journal of human genetics, 93(3), 545-554. https://doi.org/10.1016/j.ajhg.2013.07.010