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

摘要: Background: Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described. Methods: We conducted case–control genome-wide association study aTRH among persons treated for hypertension, using data from 10 cohorts European ancestry (EA) and 5 African (AA). Cases were with 3 different antihypertensive medication classes had blood pressure (BP) above goal (systolic BP ≥ 140 mm Hg and/or diastolic 90 Hg) or 4 more regardless control (nEA = 931, nAA 228). Both normotensive group treatment-responsive considered separate analyses. Normotensive controls untreated 14,210, 2,480) systolic BP/diastolic < 140/90 Hg. Treatment-responsive 5,266, 1,817) at (<140/90 Hg), while one class. Individual used logistic regression adjustment age, sex, site, principal components to examine the single-nucleotide polymorphisms status. Inverse variance-weighted fixed-effects meta-analyses carried out METAL. Results: The known locus, CASZ1, was top finding EAs (P 1.1 × 10−8) race-combined analysis 1.5 10−9) (rs12046278, odds ratio 0.71 (95% confidence interval: 0.6–0.8)). Single-nucleotide this locus robustly replicated Million Veterans Program (MVP) consideration group. There no statistically significant findings analyses including controls. Conclusion: This genomic effort identified CASZ1 as an risk locus.