Genome-wide association analysis of blood pressure traits in nearly 30,000 African ancestry individuals reveals a common set of associated genes in African and non-African populations. N. Franceschini1, E. Fox2, Z. Zhang3, T. Edwards4, M. Nalls5, Y. Sung6, B. Tayo7, Y. Sun8, O. Gottesman9, A. Adeyemo10, A. Johnson11, J. Young12, K. Rice13, H. Tang14, J. Smith15, G. Ehret16, A. Morrison17, E. Boerwinkle17, B. Psaty18, D. Arnett19, S. Redline20, R. Cooper7, N. Risch21, D. Rao6, J. Rotter22, A. Chakravarti16, A. Reiner23, D. Levy11, B. Keating24, X. Zhu3, the AGEN Consortium 1) Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC; 2) Department of Medicine, University of Mississippi Medical Center, Jackson, MS; 3) Department of Epidemiology & Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH; 4) Center for Human Genetics Research, Vanderbilt Epidemiology Center, Department of Medicine, Vanderbilt University, Nashville, TN; 5) Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD; 6) Division of Biostatistics, Washington University School of Medicine, St. Louis, MO; 7) Department of Preventive Medicine and Epidemiology, Loyola University Chicago Stritch School of Medicine, Maywood, IL; 8) Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA; 9) The Charles Bronfman Institute for Personalized Medicine, Mount Sinai School of Medicine, New York, NY; 10) Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD; 11) Center for Population Studies, National Heart, Lung, and Blood Institute, Framingham, MA; 12) Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; 13) Department of Biostatistics, University of Washington, Seattle, WA; 14) Department of Genetics, Stanford University School of Medicine, Stanford, CA; 15) Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI; 16) Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; 17) Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston Houston TX; 18) Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA; 19) Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL; 20) Department of Medicine, Harvard Medical School, Boston, MA; 21) Institute for Human Genetics, Department of Epidemiology and Biostatistics, University of California, San Francisco CA; 22) Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA; 23) Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; 24) Department of Pediatrics, University of Pennsylvania, Philadelphia, PA.
High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease among African Americans compared with other U.S. ethnic/racial groups. Thus far, African ancestry BP genome-wide association studies (GWAS) have identified few validated variants for BP. We report on a large GWAS meta-analysis of BP in individuals of African ancestry that includes 29,378 individuals from 19 discovery cohorts, followed by replication in additional samples of individuals of African (n=10,386), European (n=69,395), and East Asian (n=19,601) ancestry. In the discovery African ancestry meta-analyses, we selected 45 independent single nucleotide polymorphisms (SNPs) at a pre-specified threshold (P<1.0×10-5) that were carried forward for replication. SNPs in five loci replicated in African, European or East Asians when adjusting for multiple testing, reaching genome-wide significance for either systolic or diastolic BP in trans-ethnic meta-analysis (EVX1-HOXA, P=2.1x10-12, ULK4, P=2.1x10-13, RSPO3, P=2.43x10-11, PLEKHG1, P=1.9x10-11, SOX6, P=5.12x10-10). Three of these BP loci (EVX1-HOXA, RSPO3 and PLEKHG1) have not been previously reported for BP traits. We also identified allelic heterogeneity at the SOX6 locus, and provided evidence for fine mapping in four validated BP loci. Our findings suggest that BP loci may have significant effects across populations of different ancestry and also demonstrate that multi-ethnic samples are a key component in identification, fine mapping and understanding trait variability.
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