Genome wide association study of apparent treatment resistant hypertension in the CHARGE consortium: the CHARGE pharmacogenetics working group

Irvin, M. R. et al. (2019) Genome wide association study of apparent treatment resistant hypertension in the CHARGE consortium: the CHARGE pharmacogenetics working group. American Journal of Hypertension, 32(12), pp. 1146-1153. (doi: 10.1093/ajh/hpz150) (PMID:31545351)

[img] Text
201236.pdf - Accepted Version

927kB

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott J, Professor David and Ford, Professor Ian
Authors: Irvin, M. R., Sitlani, C. M., Floyd, J. S., Psaty, B. M., Bis, J. C., Wiggins, K. L., Whitsel, E. A., Sturmer, T., Stewart, J., Raffield, L., Sun, F., Liu, C.-T., Xu, H., Cupples, A. L., Tanner, R. M., Rossing, P., Smith, A., Zilhão, N. R., Launer, L. J., Noordam, R., Rotter, J. I., Yao, J., Li, X., Guo, X., Limdi, N., Sundaresan, A., Lange, L., Correa, A., Stott, D. J., Ford, I., Jukema, J. W., Gudnason, V., Mook-Kanamori, D. O., Trompet, S., Palmas, W., Warren, H. R., Hellwege, J. N., Giri, A., O'Donnell, C., Hung, A. M., Edwards, T. L., Ahluwalia, T. S., Arnett, D. K., and Avery, C. L.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:American Journal of Hypertension
Publisher:Oxford University Press
ISSN:0895-7061
ISSN (Online):1941-7225
Published Online:23 September 2019
Copyright Holders:Copyright © 2019 American Journal of Hypertension Ltd
First Published:First published in American Journal of Hypertension 32(12):1146-1153
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record