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Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group.

TitleGenome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group.
Publication TypeJournal Article
Year of Publication2019
AuthorsIrvin MR, Sitlani CM, Floyd JS, Psaty BM, Bis JC, Wiggins KL, Whitsel EA, Sturmer T, Stewart J, Raffield L, Sun F, Liu C-T, Xu H, Cupples AL, Tanner RM, Rossing P, Smith A, Zilhão NR, Launer LJ, Noordam R, Rotter JI, Yao J, Li X, Guo X, Limdi N, Sundaresan A, Lange L, Correa A, Stott DJ, Ford I, J Jukema W, Gudnason V, Mook-Kanamori DO, Trompet S, Palmas W, Warren HR, Hellwege JN, Giri A, O'Donnell C, Hung AM, Edwards TL, Ahluwalia TS, Arnett DK
Secondary AuthorsAvery CL
JournalAm J Hypertens
Volume32
Issue12
Pagination1146-1153
Date Published2019 11 15
ISSN1941-7225
KeywordsAfrican Americans, Aged, Antihypertensive Agents, Blood Pressure, Case-Control Studies, DNA (Cytosine-5-)-Methyltransferases, DNA-Binding Proteins, Drug Resistance, Dystrophin-Associated Proteins, Europe, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension, Male, Middle Aged, Myosin Heavy Chains, Myosin Type V, Neuropeptides, Pharmacogenetics, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Transcription Factors, United States
Abstract

BACKGROUND: Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described.

METHODS: We conducted a case-control genome-wide association study of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg) or 4 or more medication classes regardless of BP control (nEA = 931, nAA = 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (nEA = 14,210, nAA = 2,480) and had systolic BP/diastolic BP

RESULTS: The known hypertension locus, CASZ1, was a top finding among EAs (P = 1.1 × 10-8) and in the race-combined analysis (P = 1.5 × 10-9) using the normotensive control group (rs12046278, odds ratio = 0.71 (95% confidence interval: 0.6-0.8)). Single-nucleotide polymorphisms in this locus were robustly replicated in the Million Veterans Program (MVP) study in consideration of a treatment-responsive control group. There were no statistically significant findings for the discovery analyses including treatment-responsive controls.

CONCLUSION: This genomic discovery effort for aTRH identified CASZ1 as an aTRH risk locus.

DOI10.1093/ajh/hpz150
Alternate JournalAm J Hypertens
PubMed ID31545351
PubMed Central IDPMC6856621
Grant ListK12 HD043483 / HD / NICHD NIH HHS / United States
K24 HL133373 / HL / NHLBI NIH HHS / United States
S10 OD023680 / OD / NIH HHS / United States