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

TitleSingle-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.
Publication TypePublication
Year2017
AuthorsLiang J, Le TH, Edwards DRVelez, Tayo BO, Gaulton KJ, Smith JA, Lu Y, Jensen RA, Chen G, Yanek LR, Schwander K, Tajuddin SM, Sofer T, Kim W, Kayima J, McKenzie CA, Fox E, Nalls MA, J Young H, Sun YV, Lane JM, Cechova S, Zhou J, Tang H, Fornage M, Musani SK, Wang H, Lee J, Adeyemo A, Dreisbach AW, Forrester T, Chu P-L, Cappola A, Evans MK, Morrison AC, Martin LW, Wiggins KL, Hui Q, Zhao W, Jackson RD, Ware EB, Faul JD, Reiner AP, Bray M, Denny JC, Mosley TH, Palmas W, Guo X, Papanicolaou GJ, Penman AD, Polak JF, Rice K, Taylor KD, Boerwinkle E, Bottinger EP, Liu K, Risch N, Hunt SC, Kooperberg C, Zonderman AB, Laurie CC, Becker DM, Cai J, Loos RJF, Psaty BM, Weir DR, Kardia SLR, Arnett DK, Won S, Edwards TL, Redline S, Cooper RS, Rao DC, Rotter JI, Rotimi C, Levy D, Chakravarti A, Zhu X, Franceschini N
JournalPLoS Genet
Volume13
Issue5
Paginatione1006728
Date Published2017 May
ISSN1553-7404
KeywordsAfrican Americans, Animals, Basic Helix-Loop-Helix Transcription Factors, blood pressure, Cadherins, Case-Control Studies, Female, Genetic Loci, genome-wide association study, Humans, Hypertension, Male, Membrane Proteins, Mice, Multifactorial Inheritance, Polymorphism, Single Nucleotide
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.

DOI10.1371/journal.pgen.1006728
Alternate JournalPLoS Genet
PubMed ID28498854
PubMed Central IDPMC5446189
Grant ListU01 HG007417 / HG / NHGRI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL128782 / HL / NHLBI NIH HHS / United States
R01 GM073059 / GM / NIGMS NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
S10 OD018522 / OD / NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
R01 HL055673 / HL / NHLBI NIH HHS / United States
R01 DK094907 / DK / NIDDK NIH HHS / United States
R21 HL123677 / HL / NHLBI NIH HHS / United States
R21 HL121429 / HL / NHLBI NIH HHS / United States
T32 HL007567 / HL / NHLBI NIH HHS / United States
MS#: 
0480
Manuscript Lead/Corresponding Author Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
ECI: 
Yes
Manuscript Status: 
Published