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

Journal: American Journal Of Human Genetics
Published:
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.

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