|Title||Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Irvin 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 Authors||Avery CL|
|Journal||Am J Hypertens|
|Date Published||2019 11 15|
|Keywords||African 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|
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.
|Alternate Journal||Am J Hypertens|
|PubMed Central ID||PMC6856621|
|Grant List||K12 HD043483 / HD / NICHD NIH HHS / United States |
K24 HL133373 / HL / NHLBI NIH HHS / United States
S10 OD023680 / OD / NIH HHS / United States