Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations Public Deposited

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  • Liang, Jingjing
    • Other Affiliation: Department of Epidemiology & Biostatistics; School of Medicine; Case Western Reserve University
  • Le, Thu H.
    • Other Affiliation: Department of Medicine; Division of Nephrology; University of Virginia
  • Edwards, Digna R. Velez
    • Other Affiliation: Department of Obstetrics and Gynecology; Institute for Medicine and Public Health; Vanderbilt Genetics Institute; Vanderbilt University Medical Center
  • Tayo, Bamidele O.
    • Other Affiliation: Department of Public Health Sciences; Loyola University Chicago Stritch School of Medicine
  • Gaulton, Kyle J.
    • Other Affiliation: Department of Pediatrics; University of California San Diego
  • Smith, Jennifer A.
    • ORCID: 0000-0002-3575-5468
    • Other Affiliation: Department of Epidemiology; School of Public Health; University of Michigan
  • Lu, Yingchang
    • Other Affiliation: Division of Epidemiology; Department of Medicine; Vanderbilt-Ingram Cancer Center; Vanderbilt Epidemiology Center; Vanderbilt University School of Medicine
  • Jensen, Richard A.
    • Other Affiliation: Cardiovascular Health Research Unit; Department of Medicine; University of Washington
  • Chen, Guanjie
    • Other Affiliation: Center for Research on Genomics and Global Health; National Human Genome Research Institute; National Institutes of Health
  • Yanek, Lisa R.
    • ORCID: 0000-0001-7117-1075
    • Other Affiliation: Department of Medicine; Johns Hopkins University School of Medicine
  • Schwander, Karen
    • Other Affiliation: Division of Biostatistics; School of Medicine; Washington University in St. Louis
  • Tajuddin, Salman M.
    • ORCID: 0000-0002-7919-8528
    • Other Affiliation: Laboratory of Epidemiology and Population Sciences; National Institute on Aging; National Institutes of Health
  • Sofer, Tamar
    • ORCID: 0000-0001-8520-8860
    • Other Affiliation: Department of Biostatistics; University of Washington
  • Kim, Wonji
    • ORCID: 0000-0002-1249-797X
    • Other Affiliation: Interdisciplinary Program of Bioinformatics; Seoul National University
  • Kayima, James
    • Other Affiliation: Division of Adult Cardiology Heart Institute; Makerere University College of Health Sciences
  • McKenzie, Colin A.
    • Other Affiliation: Tropical Metabolism Research Unit; Caribbean Institute for Health Research; University of the West Indies
  • Fox, Ervin
    • Other Affiliation: Department of Preventive Medicine; University of Mississippi Medical Center
  • Nalls, Michael A.
    • Other Affiliation: Data Tecnica International; Glen Echo; MD and Laboratory of Neurogenetics; National Institute on Aging; National Institute of Health
  • Young, J. Hunter
    • Other Affiliation: Department of Medicine; Johns Hopkins University School of Medicine
  • Sun, Yan V.
    • ORCID: 0000-0002-2838-1824
    • Other Affiliation: Department of Epidemiology; Rollins School of Public Health; Emory University
  • Lane, Jacqueline M.
    • Other Affiliation: Center for Genomic Medicine; Massachusetts General Hospital
  • Cechova, Sylvia
    • ORCID: 0000-0001-7631-7707
    • Other Affiliation: Department of Medicine; Division of Nephrology; University of Virginia
  • Zhou, Jie
    • Other Affiliation: Center for Research on Genomics and Global Health; National Human Genome Research Institute; National Institutes of Health
  • Tang, Hua
    • Other Affiliation: Department of Genetics; Stanford University School of Medicine
  • Fornage, Myriam
    • Other Affiliation: Institute of Molecular Medicine and Human Genetics Center; University of Texas Health Science Center at Houston
  • Musani, Solomon K.
    • Other Affiliation: Department of Preventive Medicine; University of Mississippi Medical Center
  • Wang, Heming
    • Other Affiliation: Department of Epidemiology & Biostatistics; School of Medicine; Case Western Reserve University
  • Lee, Juyoung
    • ORCID: 0000-0002-1729-2383
    • Other Affiliation: Division of Structural and Functional Genomics; Center for Genome Science; Korea National Institute of Health
  • Adeyemo, Adebowale
    • ORCID: 0000-0002-3105-3231
    • Other Affiliation: Center for Research on Genomics and Global Health; National Human Genome Research Institute; National Institutes of Health
  • Dreisbach, Albert W.
    • ORCID: 0000-0002-9658-0198
    • Other Affiliation: Department of Preventive Medicine; University of Mississippi Medical Center
  • Forrester, Terrence
    • Other Affiliation: Tropical Metabolism Research Unit; Caribbean Institute for Health Research; University of the West Indies
  • Chu, Pei-Lun
    • Other Affiliation: Department of Internal Medicine; Graduate Institute of Biomedical and Pharmaceutical Science; College of Medicine; Fu Jen Catholic University; New Taipei City
  • Cappola, Anne
    • ORCID: 0000-0002-0883-9754
    • Other Affiliation: Division of Endocrinology; Diabetes and Metabolism; Perelman School of Medicine at the University of Pennsylvania
  • Evans, Michele K.
    • Other Affiliation: Laboratory of Epidemiology and Population Sciences; National Institute on Aging; National Institutes of Health
  • Morrison, Alanna C.
    • Other Affiliation: Human Genetics Center; School of Public Health; University of Texas Health Science Center
  • Martin, Lisa W.
    • Other Affiliation: The George Washington University School of Medicine and Health Sciences
  • Wiggins, Kerri L.
    • Other Affiliation: Cardiovascular Health Research Unit; Department of Medicine; University of Washington
  • Hui, Qin
    • Other Affiliation: Department of Epidemiology; Rollins School of Public Health; Emory University
  • Zhao, Wei
    • Other Affiliation: Department of Epidemiology; School of Public Health; University of Michigan
  • Jackson, Rebecca D.
    • Other Affiliation: Department of Internal Medicine; Ohio State University
  • Ware, Erin B.
    • Other Affiliation: Survey Research Center; Institute for Social Research; University of Michigan
  • Faul, Jessica D.
    • Other Affiliation: Survey Research Center; Institute for Social Research; University of Michigan
  • Reiner, Alex P.
    • Other Affiliation: Division of Public Health Sciences; Fred Hutchinson Cancer Research Center
  • Bray, Michael
    • Other Affiliation: Department of Obstetrics and Gynecology; Institute for Medicine and Public Health; Vanderbilt Genetics Institute; Vanderbilt University Medical Center
  • Denny, Joshua C.
    • Other Affiliation: Department of Biomedical Informatics; Department of Medicine; Vanderbilt University Medical Center
  • Mosley, Thomas H.
    • Other Affiliation: Department of Preventive Medicine; University of Mississippi Medical Center
  • Palmas, Walter
    • Other Affiliation: Department of Medicine; Columbia University
  • Guo, Xiuqing
    • Other Affiliation: Medical Genetics Institute; Cedars-Sinai Medical Center
  • Papanicolaou, George J.
    • ORCID: 0000-0003-1036-4329
    • Other Affiliation: Division of Cardiovascular Sciences; National Heart Lung and Blood Institute; National Institutes of Health
  • Penman, Alan D.
    • ORCID: 0000-0002-6745-4635
    • Other Affiliation: Department of Preventive Medicine; University of Mississippi Medical Center
  • Polak, Joseph F.
    • Other Affiliation: Tufts Medical Center; Tufts University School of Medicine
  • Rice, Kenneth
    • ORCID: 0000-0001-5779-4495
    • Other Affiliation: Department of Biostatistics; University of Washington
  • Taylor, Ken D.
    • Other Affiliation: Institute for Translational Genomics and Population Sciences; Los Angeles Biomedical Research Institute and Department of Pediatrics; Harbor-UCLA Medical Center
  • Boerwinkle, Eric
    • Other Affiliation: Human Genetics Center; School of Public Health; University of Texas Health Science Center
  • Bottinger, Erwin P.
    • Other Affiliation: The Charles Bronfman Institute for Personalized Medicine; Icahn School of Medicine at Mount Sinai
  • Liu, Kiang
    • Other Affiliation: Department of Preventive Medicine; Northwestern University Medical School
  • Risch, Neil
    • Other Affiliation: Institute for Human Genetics; University of California
  • Hunt, Steven C.
    • Other Affiliation: Cardiovascular Genetics; University of Utah
  • Kooperberg, Charles
    • Other Affiliation: Division of Public Health Sciences; Fred Hutchinson Cancer Research Center
  • Zonderman, Alan B.
    • Other Affiliation: Laboratory of Epidemiology and Population Sciences; National Institute on Aging; National Institutes of Health
  • Laurie, Cathy C.
    • ORCID: 0000-0003-2572-4040
    • Other Affiliation: Department of Biostatistics; University of Washington
  • Becker, Diane M.
    • Other Affiliation: Department of Medicine; Johns Hopkins University School of Medicine
  • Cai, Jianwen
    • Affiliation: Gillings School of Global Public Health, Department of Biostatistics
  • Loos, Ruth J. F.
    • Other Affiliation: The Mindich Child Health and Development Institute; Ichan School of Medicine at Mount Sinai
  • Psaty, Bruce M.
    • Other Affiliation: Kaiser Permanente Washington Health Research Institute
  • Weir, David R.
    • Other Affiliation: Survey Research Center; Institute for Social Research; University of Michigan
  • Kardia, Sharon L. R.
    • Other Affiliation: Department of Epidemiology; School of Public Health; University of Michigan
  • Arnett, Donna K.
    • Other Affiliation: University of Kentucky; College of Public Health
  • Won, Sungho
    • Other Affiliation: Interdisciplinary Program of Bioinformatics; Seoul National University
  • Edwards, Todd L.
    • Other Affiliation: Division of Epidemiology; Department of Medicine; Institute of Medicine and Public Health; Vanderbilt Genetics Institute; Vanderbilit University Medical Center
  • Redline, Susan
    • Other Affiliation: Department of Medicine; Brigham and Women's Hospital; Harvard Medical School
  • Cooper, Richard S.
    • Other Affiliation: Department of Public Health Sciences; Loyola University Chicago Stritch School of Medicine
  • Rao,
    • Other Affiliation: Division of Biostatistics; School of Medicine; Washington University in St. Louis
  • Rotter, Jerome I.
    • ORCID: 0000-0001-7191-1723
    • Other Affiliation: Institute for Translational Genomics and Population Sciences; Los Angeles Biomedical Research Institute and Department of Pediatrics; Harbor-UCLA Medical Center
  • Rotimi, Charles
    • Other Affiliation: Center for Research on Genomics and Global Health; National Human Genome Research Institute; National Institutes of Health
  • Levy, Daniel
    • Other Affiliation: Population Sciences Branch; National Heart; Lung; and Blood Institute of the National Institutes of Health
  • Chakravarti, Aravinda
    • Other Affiliation: McKusick-Nathans Institute of Genetic Medicine; Johns Hopkins University School of Medicine
  • Zhu, Xiaofeng
    • Other Affiliation: Department of Epidemiology & Biostatistics; School of Medicine; Case Western Reserve University
  • Franceschini, Nora
    • ORCID: 0000-0001-9755-2175
    • Affiliation: Gillings School of Global Public Health
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.
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DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • PLoS Genetics
Journal volume
  • 13
Journal issue
  • 5
Page start
  • e1006728
Language
  • English
ISSN
  • 1553-7390
  • 1553-7404
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