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PLoS Genet. 2017 May 12;13(5):e1006728. doi: 10.1371/journal.pgen.1006728. eCollection 2017 May.

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

Author information

1
Department of Epidemiology & Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH, United States of America.
2
Department of Medicine, Division of Nephrology, University of Virginia, Charlottesville, Virginia, United States of America.
3
Department of Obstetrics and Gynecology, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
4
Department of Public Health Sciences, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, United States of America.
5
Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
6
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
7
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America.
8
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.
9
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
10
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America.
11
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
12
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
13
Division of Biostatistics, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America.
14
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
15
Department of Biostatistics, University of Washington, Seattle, Washington, United States of America.
16
Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul, Republic of Korea.
17
Division of Adult Cardiology, Uganda Heart Institute, Makerere University College of Health Sciences, Kampala, Uganda.
18
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
19
Tropical Metabolism Research Unit, Caribbean Institute for Health Research, University of the West Indies, Mona, Jamaica.
20
Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
21
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.
22
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America.
23
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
24
Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
25
Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States of America.
26
Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
27
Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, United States of America.
28
Division of Structural and Functional Genomics, Center for Genome Science, Korea National Institute of Health, Cheongju, Republic of Korea.
29
Department of Internal Medicine, Graduate Institute of Biomedical and Pharmaceutical Science, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
30
Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States of America.
31
Human Genetics Center, School of Public Health, University of Texas Health Science Center, Houston, Texas, United States of America.
32
The George Washington University School of Medicine and Health Sciences, Washington DC. United States of America.
33
Department of Internal Medicine, Ohio State University, Columbus, Ohio, United States of America.
34
Survey Research Center, Institute for Social Research, University of Michigan Ann Arbor, Michigan, United States of America.
35
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
36
Department of Biomedical Informatics, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
37
Department of Medicine, Columbia University, New York City, New York, United States of America.
38
Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America.
39
Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
40
Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
41
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA.
42
Department of Preventive Medicine, Northwestern University Medical School, Chicago, Illinois, United States of America.
43
Institute for Human Genetics, University of California, San Francisco, California, United States of America.
44
Cardiovascular Genetics, University of Utah, Salt Lake City, Utah, United States of America.
45
Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States of America.
46
The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York City, New York, United States of America.
47
Kaiser Permanente Washington Health Research Institute, Seattle, Washington, United States of America.
48
University of Kentucky, College of Public Health, Lexington, KY.
49
Department of Public Health Science, Seoul National University, Seoul, Republic of Korea.
50
Division of Epidemiology, Department of Medicine, Institute of Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilit University Medical Center, Nashville, Tennessee, United States of America.
51
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
52
Population Sciences Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, and the Framingham Heart Study, Framingham, Massachusetts, United States of America.
53
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
54
Epidemiology, Gilling School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.

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.

PMID:
28498854
PMCID:
PMC5446189
DOI:
10.1371/journal.pgen.1006728
[Indexed for MEDLINE]
Free PMC Article

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