Variant Discovery and Fine Mapping of Genetic Loci Associated with Blood Pressure Traits in Hispanics and African Americans
Year: 2016
Type: article
Study design: Observational Study
Abstract: Despite the substantial burden of hypertension in US minority populations, few genetic studies of blood pressure have been conducted in Hispanics and African Americans, and it is unclear whether many of the established loci identified in European-descent populations contribute to blood pressure variation in non-European descent populations. Using the Metabochip array, we sought to characterize the genetic architecture of previously identified blood pressure loci, and identify novel cardiometabolic variants related to systolic and diastolic blood pressure in a multi-ethnic US population including Hispanics (n = 19,706) and African Americans (n = 18,744). Several known blood pressure loci replicated in African Americans and Hispanics. Fourteen variants in three loci (KCNK3, FGF5, ATXN2-SH2B3) were significantly associated with blood pressure in Hispanics. The most significant diastolic blood pressure variant identified in our analysis, rs2586886/KCNK3 (P = 5.2 x 10-9), also replicated in independent Hispanic and European-descent samples. African American and trans-ethnic meta-analysis data identified novel variants in the FGF5, ULK4 and HOXA-EVX1 loci, which have not been previously associated with blood pressure traits. Our identification and independent replication of variants in KCNK3, a gene implicated in primary hyperaldosteronism, as well as a variant in HOTTIP (HOXA-EVX1) suggest that further work to clarify the roles of these genes may be warranted. Overall, our findings suggest that loci identified in European descent populations also contribute to blood pressure variation in diverse populations including Hispanics and African Americans-populations that are understudied for hypertension genetic risk factors.
Source: PLoS ONE
Authors: Nora Franceschini, Cara L. Carty, Yingchang Lu, Ran Tao, Yun Ju Sung, Ani Manichaikul, Jeff Haessler, Myriam Fornage, Karen Schwander, Niha Zubair, Stephanie Bien, Lucia A. Hindorff, Xiuqing Guo, Suzette J. Bielinski, Georg Ehret, Joel D. Kaufman, Stephen S. Rich, Christopher S. Carlson, Erwin P. Bottinger, Kari E. North, D. C. Rao, Aravinda Chakravarti, Paula Q. Barrett, Ruth J. F. Loos, Steven Buyske, Charles Kooperberg
Institutions: University of North Carolina at Chapel Hill, Children's National, George Washington University, Icahn School of Medicine at Mount Sinai, Washington University in St. Louis, University of Virginia, Fred Hutch Cancer Center, The University of Texas Health Science Center at Houston, National Institutes of Health, National Human Genome Research Institute, University of California, Los Angeles, Los Angeles Medical Center, Harbor–UCLA Medical Center, Mayo Clinic, Johns Hopkins University, Johns Hopkins Medicine, University Hospital of Geneva, University of Washington, Rutgers, The State University of New Jersey
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: Andrea and Charles Bronfman Philanthropies, Broad Institute, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1028935811, G1052397333, FHCRC High-Performance Computing Cluster, G1135917780, Multi-Ethnic Study of Atherosclerosis (MESA) Study, G1243299691, MESA, Epidemiology of putative genuine genetic variant: The Women's Health Intiative, G1409423729, Trans-ethnic meta-analysis of blood pressure in African and European ancestries, G1527150935, G1686417863, G1691174148, UCLA Clinical and Translational Science Institute, G173303992, G1941623656, G1947136479, Two-pore domain potassium channels and aldosterone secretion, Adaptive Statistical Methods for Genetic Association Studies, G2262782284, G2273349799, Epidemiology of Putative Causal Variants in the Multiethnic Cohort, G2412562481, MESA, Institute for Clinical and Translational Research (UL1), MESA Family Study, G2663518188, G2818629771, MESA, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, DISCOVER Center: Cardiovascular Disease and Traffic-Related Air Pollution, G3114902838, UCLA Clinical and Translational Science Institute, MESA Family Study, G3342643523, G3410686264, G3462919067, G3545534745, G3647016462, G3687594596, G3692229207, G36937976, GWA for Gene-Environment Interaction Effects Influencing CHD, MESA, G399481048, Clinical and Translational Science Institute at Children's National, G412187901, NHGRI EpiGenVar Coordinating Center, TITLE: MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA), G4512137732, G457330776, OPTION 3. 4/1/2014 - 3/31/2015. MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) - READING CENTER, NHLBI, MESA Family Study, MESA, MESA Family Study, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G5547620395, G5624510383, G567847597, Multi-Scale Biology of Atherosclerosis in the Cellular Adhesion Pathway, G5787256936, G6095866717, G619791618, G6359107525, Institute for Clinical and Translational Research, MESA, G6514094751, G6548750934, SNP HEALTH ASSOCIATION RESOURCE (SHARE), G673128162, G7055397874, MESA Family Study, MESA, Genetic Epidemiology of Causal Variants Across the Life Course, Clinical and Translational Science Award, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8536616440, G8541424066, Exonic variants and their relation to complex traits in minorities of the WHI, UNC Center for Environmental Health and Susceptibility, Diabetes Research Center (DRC), NYR-Diabetes Research Center (NYR-DRC), From GWAS loci to blood pressure genes, variants & mechanisms - Renewal
OpenAlex ID: W2530913842