Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations
Creators: name: Liang, Jingjing
name: Le, Thu H.
name: Velez Edwards, Digna R.
name: Tayo, Bamidele O.
name: Gaulton, Kyle J.
name: Smith, Jennifer A.
name: Lu, Yingchang
name: Jensen, Richard A.
name: Chen, Guanjie
name: Yanek, Lisa R.
name: Schwander, Karen
name: Tajuddin, Salman M.
name: Sofer, Tamar
name: Kim, Wonji
name: Kayima, James
name: McKenzie, Colin A.
name: Fox, Ervin
name: Nalls, Michael A.
name: Young, J. Hunter
name: Sun, Yan V.
name: Lane, Jacqueline M.
name: Cechova, Sylvia
name: Zhou, Jie
name: Tang, Hua
name: Fornage, Myriam
name: Musani, Solomon K.
name: Wang, Heming
name: Lee, Juyoung
name: Adeyemo, Adebowale
name: Dreisbach, Albert W.
name: Forrester, Terrence
name: Chu, Pei-Lun
name: Cappola, Anne R.
name: Evans, Michele K.
name: Morrison, Alanna C.
name: Martin, Lisa W.
name: Wiggins, Kerri L.
name: Hui, Qin
name: Zhao, Wei
name: Jackson, Rebecca D.
name: Ware, Erin B.
name: Faul, Jessica D.
name: Reiner, Alex P.
name: Bray, Michael
name: Denny, Joshua C.
name: Mosley, Thomas H.
name: Palmas, Walter R.
name: Guo, Xiuqing
name: Papanicolaou, George J.
name: Penman, Alan D.
name: Polak, Joseph F.
name: Rice, Kenneth
name: Taylor, Ken D.
name: Boerwinkle, Eric
name: Bottinger, Erwin P.
name: Liu, Kiang
name: Risch, Neil
name: Hunt, Steven C.
name: Kooperberg, Charles
name: Zonderman, Alan B.
name: Laurie, Cathy C.
name: Becker, Diane M.
name: Cai, Jianwen
name: Loos, Ruth J. F.
name: Psaty, Bruce M.
name: Weir, David R.
name: Kardia, Sharon L. R.
name: Arnett, Donna K.
name: Won, Sungho
name: Edwards, Todd L.
name: Redline, Susan
name: Cooper, Richard
name: Rao, D. C.
name: Rotter, Jerome I.
name: Rotimi, Charles N.
name: Levy, Daniel
name: Chakravarti, Aravinda
name: Zhu, Xiaofeng
name: Franceschini, Nora
Publisher: name: Columbia University
Year: 2017
Subjects: subject: Epidemiology
subject: Biometry
subject: Genetics
subject: FOS: Biological sciences
subject: Hypertension
subject: African Americans

description: 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 &lt; 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.