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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 < 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.
SUBMITTER: Irvin MR
PROVIDER: S-EPMC6856621 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Irvin Marguerite R MR Sitlani Colleen M CM Floyd James S JS Psaty Bruce M BM Bis Joshua C JC Wiggins Kerri L KL Whitsel Eric A EA Sturmer Til T Stewart James J Raffield Laura L Sun Fangui F Liu Ching-Ti CT Xu Hanfei H Cupples Adrienne L AL Tanner Rikki M RM Rossing Peter P Smith Albert A Zilhão Nuno R NR Launer Lenore J LJ Noordam Raymond R Rotter Jerome I JI Yao Jie J Li Xiaohui X Guo Xiuqing X Limdi Nita N Sundaresan Aishwarya A Lange Leslie L Correa Adolfo A Stott David J DJ Ford Ian I Jukema J Wouter JW Gudnason Vilmundur V Mook-Kanamori Dennis O DO Trompet Stella S Palmas Walter W Warren Helen R HR Hellwege Jacklyn N JN Giri Ayush A O'donnell Christopher C Hung Adriana M AM Edwards Todd L TL Ahluwalia Tarunveer S TS Arnett Donna K DK Avery Christy L CL
American journal of hypertension 20191101 12
<h4>Background</h4>Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described.<h4>Methods</h4>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 diastol ...[more]