Cited 10 times since 2019 (1.9 per year) source: EuropePMC American journal of hypertension, Volume 32, Issue 12, 1 1 2019, Pages 1146-1153 Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group. Irvin MR, Sitlani CM, Floyd JS, Psaty BM, Bis JC, Wiggins KL, Whitsel EA, Sturmer T, Stewart J, Raffield L, Sun F, Liu CT, 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, Jukema JW, 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, Avery CL
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 < 140/90 mm Hg. Treatment-responsive controls (nEA = 5,266, nAA = 1,817) had BP at goal (<140/90 mm Hg), while treated with one antihypertensive medication class. Individual cohorts used logistic regression with adjustment for age, sex, study site, and principal components for ancestry to examine the association of single-nucleotide polymorphisms with case-control status. Inverse variance-weighted fixed-effects meta-analyses were carried out using METAL.
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.
