Jingjing Liang, CASE School of Medicine
Thu H. Le, University of Virginia School of Medicine
Digna R.Velez Edwards, Vanderbilt University Medical Center
Bamidele O. Tayo, Stritch School of Medicine
Kyle J. Gaulton, University of California, San Diego
Jennifer A. Smith, University of Michigan, Ann Arbor
Yingchang Lu, Icahn School of Medicine at Mount Sinai
Richard A. Jensen, University of Washington School of Medicine
Guanjie Chen, National Human Genome Research Institute (NHGRI)
Lisa R. Yanek, Johns Hopkins University School of Medicine
Karen Schwander, Washington University in St. Louis
Salman M. Tajuddin, National Institutes of Health (NIH)
Tamar Sofer, University of Washington
Wonji Kim, Seoul National University
James Kayima, Makerere University College of Health Sciences
Colin A. McKenzie, Caribbean Institute for Health Research
Ervin Fox, University of Mississippi Medical Center
Michael A. Nalls, National Institutes of Health (NIH)
J. Hunter Young, Johns Hopkins University School of Medicine
Yan V. Sun, Rollins School of Public Health
Jacqueline M. Lane, Massachusetts General Hospital
Sylvia Cechova, University of Virginia School of Medicine
Jie Zhou, National Human Genome Research Institute (NHGRI)
Hua Tang, Stanford University School of Medicine
Myriam Fornage, McGovern Medical School
Solomon K. Musani, University of Mississippi Medical Center
Heming Wang, CASE School of Medicine
Juyoung Lee, Korea National Institute of Health
Adebowale Adeyemo, National Human Genome Research Institute (NHGRI)
Albert W. Dreisbach, University of Mississippi Medical Center
Terrence Forrester, Caribbean Institute for Health Research
Pei Lun Chu, Fu Jen Catholic University College of Medicine
Anne Cappola, University of Pennsylvania Perelman School of Medicine

Document Type

Article

Publication Date

5-1-2017

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.

Publication Source (Journal or Book title)

PLoS Genetics

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