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

被引：15

作者：

Irvin, Marguerite R. ^{[1
]}

Sitlani, Colleen M. ^{[2
]}

Floyd, James S. ^{[2
]}

Psaty, Bruce M. ^{[2
,3
,4
,5
]}

Bis, Joshua C. ^{[2
]}

Wiggins, Kerri L. ^{[2
]}

Whitsel, Eric A. ^{[6
,7
]}

Sturmer, Til ^{[7
]}

Stewart, James ^{[7
]}

Raffield, Laura ^{[8
]}

Sun, Fangui ^{[9
]}

Liu, Ching-Ti ^{[9
]}

Xu, Hanfei ^{[9
]}

Cupples, Adrienne L. ^{[9
]}

Tanner, Rikki M. ^{[1
]}

Rossing, Peter ^{[10
]}

Smith, Albert ^{[11
,12
]}

Zilhao, Nuno R. ^{[11
]}

Launer, Lenore J. ^{[13
]}

Noordam, Raymond ^{[14
]}

Rotter, Jerome, I ^{[15
,16
]}

Yao, Jie ^{[15
,16
]}

Li, Xiaohui ^{[15
,16
]}

Guo, Xiuqing ^{[15
,16
]}

Limdi, Nita ^{[17
]}

Sundaresan, Aishwarya ^{[18
]}

Lange, Leslie ^{[19
]}

Correa, Adolfo ^{[20
]}

Stott, David J. ^{[21
]}

Ford, Ian ^{[22
]}

Jukema, J. Wouter ^{[23
]}

Gudnason, Vilmundur ^{[24
,25
]}

Mook-Kanamori, Dennis O. ^{[14
]}

Trompet, Stella ^{[14
]}

Palmas, Walter ^{[26
]}

Warren, Helen R. ^{[27
,28
]}

Hellwege, Jacklyn N. ^{[29
,30
]}

Giri, Ayush ^{[29
,31
]}

O'Donnell, Christopher ^{[32
,33
]}

Hung, Adriana M. ^{[29
,34
]}

Edwards, Todd L. ^{[29
,35
]}

Ahluwalia, Tarunveer S. ^{[1
,10
]}

Arnett, Donna K. ^{[36
]}

Avery, Christy L. ^{[7
]}

机构：

[1] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA

[2] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[3] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[4] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA

[5] Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA

[6] Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA

[7] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA

[8] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA

[9] Boston Univ, Dept Biostat, Boston, MD USA

[10] Steno Diabet Ctr Copenhagen, Gentofte, Denmark

[11] Iceland Heart Assoc, Kopavogur, Iceland

[12] Univ Iceland, Reykjavik, Iceland

[13] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA

[14] Leiden Univ, Dept Internal Med, Sect Gerontol & Geriatr, Med Ctr, Leiden, Netherlands

[15] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, LABioMed, Dept Pediat, Torrance, CA 90509 USA

[16] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, LABioMed, Dept Med, Torrance, CA 90509 USA

[17] Univ Alabama Birmingham, Sch Med, Dept Neurol, Birmingham, AL USA

[18] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL USA

[19] Univ Colorado Denver, Dept Med, Aurora, CO USA

[20] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA

[21] Univ Glasgow, Coll Med Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland

[22] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland

[23] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands

[24] Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands

[25] Leiden Univ, Dept Publ Hlth & Primary Care, Med Ctr, Leiden, Netherlands

[26] Columbia Univ, Dept Med, Med Ctr, New York, NY USA

[27] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England

[28] Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England

[29] Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Biomed Lab Res & Dev, 221 Kirkland Hall, Nashville, TN 37235 USA

[30] Vanderbilt Univ, Med Ctr, Div Genet Med, Dept Med,Vanderbilt Genet Inst, Nashville, TN USA

[31] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol,Div Quantitat Sci, Vanderbilt Genet Inst,Vanderbilt Epidemiol Ctr,In, Nashville, TN 37232 USA

[32] VA Boston Hlth Care Syst, Boston, MA USA

[33] Harvard Med Sch, Brigham & Womens Hosp, Sect Cardiol & Dept Med, Boston, MA 02115 USA

[34] Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol & Hypertens, Nashville, TN USA

[35] Vanderbilt Univ, Vanderbilt Genet Inst, Dept Med, Div Epidemiol,Med Ctr, Nashville, TN USA

[36] Univ Kentucky, Deans Off, Sch Publ Hlth, Lexington, KY USA

来源：

AMERICAN JOURNAL OF HYPERTENSION | 2019年 / 32卷 / 12期

基金：

美国国家卫生研究院;

关键词：

blood pressure; hypertension; genome-wide association study; severe hypertension; treatment-resistant hypertension; BLOOD-PRESSURE; LOCI; CASZ1; RISK;

D O I：

10.1093/ajh/hpz150

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

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 (n(EA) = 931, n(AA) = 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (n(EA) = 14,210, n(AA) = 2,480) and had systolic BP/diastolic BP < 140/90 mm Hg. Treatment-responsive controls (n(EA) = 5,266, n(AA) = 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 x 10(-8)) and in the race-combined analysis (P = 1.5 x 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.

引用

页码：1146 / 1153

页数：8

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