TY - JOUR
T1 - Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium
T2 - The CHARGE Pharmacogenetics Working Group
AU - Irvin, Marguerite R.
AU - Sitlani, Colleen M.
AU - Floyd, James S.
AU - Psaty, Bruce M.
AU - Bis, Joshua C.
AU - Wiggins, Kerri L.
AU - Whitsel, Eric A.
AU - Sturmer, Til
AU - Stewart, James
AU - Raffield, Laura
AU - Sun, Fangui
AU - Liu, Ching Ti
AU - Xu, Hanfei
AU - Cupples, Adrienne L.
AU - Tanner, Rikki M.
AU - Rossing, Peter
AU - Smith, Albert
AU - Zilhão, Nuno R.
AU - Launer, Lenore J.
AU - Noordam, Raymond
AU - Rotter, Jerome I.
AU - Yao, Jie
AU - Li, Xiaohui
AU - Guo, Xiuqing
AU - Limdi, Nita
AU - Sundaresan, Aishwarya
AU - Lange, Leslie
AU - Correa, Adolfo
AU - Stott, David J.
AU - Ford, Ian
AU - Wouter Jukema, J.
AU - Gudnason, Vilmundur
AU - Mook-Kanamori, Dennis O.
AU - Trompet, Stella
AU - Palmas, Walter
AU - Warren, Helen R.
AU - Hellwege, Jacklyn N.
AU - Giri, Ayush
AU - O'Donnell, Christopher
AU - Hung, Adriana M.
AU - Edwards, Todd L.
AU - Ahluwalia, Tarunveer S.
AU - Arnett, Donna K.
AU - Avery, Christy L.
N1 - Publisher Copyright:
© 2019 American Journal of Hypertension, Ltd. All rights reserved.
PY - 2019/11/15
Y1 - 2019/11/15
N2 - 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.
AB - 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.
KW - blood pressure
KW - genome-wide association study
KW - hypertension
KW - severe hypertension
KW - treatment-resistant hypertension
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U2 - 10.1093/ajh/hpz150
DO - 10.1093/ajh/hpz150
M3 - Article
C2 - 31545351
AN - SCOPUS:85075091903
SN - 0895-7061
VL - 32
SP - 1146
EP - 1153
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 12
ER -