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Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.
Liang, Jingjing; Le, Thu H; Edwards, Digna R Velez; Tayo, Bamidele O; Gaulton, Kyle J; Smith, Jennifer A; Lu, Yingchang; Jensen, Richard A; Chen, Guanjie; Yanek, Lisa R; Schwander, Karen; Tajuddin, Salman M; Sofer, Tamar; Kim, Wonji; Kayima, James; McKenzie, Colin A; Fox, Ervin; Nalls, Michael A; Young, J Hunter; Sun, Yan V; Lane, Jacqueline M; Cechova, Sylvia; Zhou, Jie; Tang, Hua; Fornage, Myriam; Musani, Solomon K; Wang, Heming; Lee, Juyoung; Adeyemo, Adebowale; Dreisbach, Albert W; Forrester, Terrence; Chu, Pei-Lun; Cappola, Anne; Evans, Michele K; Morrison, Alanna C; Martin, Lisa W; Wiggins, Kerri L; Hui, Qin; Zhao, Wei; Jackson, Rebecca D; Ware, Erin B; Faul, Jessica D; Reiner, Alex P; Bray, Michael; Denny, Joshua C; Mosley, Thomas H; Palmas, Walter; Guo, Xiuqing; Papanicolaou, George J; Penman, Alan D.
Afiliación
  • Liang J; Department of Epidemiology & Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH, United States of America.
  • Le TH; Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, Virginia, United States of America.
  • Edwards DRV; Department of Obstetrics and Gynecology, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
  • Tayo BO; Department of Public Health Sciences, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, United States of America.
  • Gaulton KJ; Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
  • Smith JA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Lu Y; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Jensen RA; The Genetics of Obesity and Related Metabolic Traits Program, Ichan School of Medicine at Mount Sinai, New York City, New York, United States of America.
  • Chen G; Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
  • Yanek LR; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America.
  • Schwander K; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
  • Tajuddin SM; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Sofer T; Division of Biostatistics, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America.
  • Kim W; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
  • Kayima J; Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
  • McKenzie CA; Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul, Republic of Korea.
  • Fox E; Division of Adult Cardiology, Uganda Heart Institute, Makerere University College of Health Sciences, Kampala, Uganda.
  • Nalls MA; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
  • Young JH; Tropical Metabolism Research Unit, Caribbean Institute for Health Research, University of the West Indies, Mona, Jamaica.
  • Sun YV; Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
  • Lane JM; Data Tecnica International, Glen Echo, MD, United States of America and Laboratory of Neurogenetics, National Institute on Aging, National Institute of Health, Bethesda, Maryland, United States of America.
  • Cechova S; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Zhou J; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America.
  • Tang H; Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
  • Fornage M; Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
  • Musani SK; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
  • Wang H; Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, Virginia, United States of America.
  • Lee J; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
  • Adeyemo A; Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
  • Dreisbach AW; Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, United States of America.
  • Forrester T; Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
  • Chu PL; Department of Epidemiology & Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH, United States of America.
  • Cappola A; Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health, Cheongju, Republic of Korea.
  • Evans MK; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
  • Morrison AC; Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
  • Martin LW; Tropical Metabolism Research Unit, Caribbean Institute for Health Research, University of the West Indies, Mona, Jamaica.
  • Wiggins KL; Department of Internal Medicine, Graduate Institute of Biomedical and Pharmaceutical Science, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
  • Hui Q; Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States of America.
  • Zhao W; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
  • Jackson RD; Human Genetics Center, School of Public Health, University of Texas Health Science Center, Houston, Texas, United States of America.
  • Ware EB; The George Washington University School of Medicine and Health Sciences, Washington DC. United States of America.
  • Faul JD; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America.
  • Reiner AP; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America.
  • Bray M; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Denny JC; Department of Internal Medicine, Ohio State University, Columbus, Ohio, United States of America.
  • Mosley TH; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Palmas W; Survey Research Center, Institute for Social Research, University of Michigan Ann Arbor, Michigan, United States of America.
  • Guo X; Survey Research Center, Institute for Social Research, University of Michigan Ann Arbor, Michigan, United States of America.
  • Papanicolaou GJ; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Penman AD; Department of Obstetrics and Gynecology, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
PLoS Genet ; 13(5): e1006728, 2017 May.
Article en En | MEDLINE | ID: mdl-28498854
ABSTRACT
Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Presión Sanguínea / Herencia Multifactorial / Sitios Genéticos / Hipertensión Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Presión Sanguínea / Herencia Multifactorial / Sitios Genéticos / Hipertensión Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos