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

Marguerite R Irvin; Colleen M Sitlani; James S Floyd; Bruce M Psaty; Joshua C Bis; Kerri L Wiggins; Eric A Whitsel; Til Sturmer; James Stewart; Laura Raffield; Fangui Sun; Ching-Ti Liu; Hanfei Xu; Adrienne L Cupples; Rikki M Tanner; Peter Rossing; Albert Smith; Nuno R Zilhão; Lenore J Launer; Raymond Noordam; Jerome I Rotter; Jie Yao; Xiaohui Li; Xiuqing Guo; Nita Limdi; Aishwarya Sundaresan; Leslie Lange; Adolfo Correa; David J Stott; Ian Ford; J Wouter Jukema; Vilmundur Gudnason; Dennis O Mook-Kanamori; Stella Trompet; Walter Palmas; Helen R Warren; Jacklyn N Hellwege; Ayush Giri; Christopher O'donnell; Adriana M Hung; Todd L Edwards; Tarunveer S. Ahluwalia; Donna K Arnett; Christy L Avery

doi:10.1093/ajh/hpz150

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

Marguerite R Irvin, Colleen M Sitlani, James S Floyd, Bruce M Psaty, Joshua C Bis, Kerri L Wiggins, Eric A Whitsel, Til Sturmer, James Stewart, Laura Raffield, Fangui Sun, Ching-Ti Liu, Hanfei Xu, Adrienne L Cupples, Rikki M Tanner, Peter Rossing, Albert Smith, Nuno R Zilhão, Lenore J Launer, Raymond NoordamJerome I Rotter, Jie Yao, Xiaohui Li, Xiuqing Guo, Nita Limdi, Aishwarya Sundaresan, Leslie Lange, Adolfo Correa, David J Stott, Ian Ford, J Wouter Jukema, Vilmundur Gudnason, Dennis O Mook-Kanamori, Stella Trompet, Walter Palmas, Helen R Warren, Jacklyn N Hellwege, Ayush Giri, Christopher O'donnell, Adriana M Hung, Todd L Edwards, Tarunveer S. Ahluwalia, Donna K Arnett, Christy L Avery

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

17 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	American Journal of Hypertension
Vol/bind	32
Udgave nummer	12
Sider (fra-til)	1146-1153
Antal sider	8
ISSN	0895-7061
DOI	https://doi.org/10.1093/ajh/hpz150
Status	Udgivet - 2019

Adgang til dokumentet

10.1093/ajh/hpz150

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856621/pdf/hpz150.pdfLicens: Andet

Citationsformater

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., ... Avery, C. L. (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), 1146-1153. https://doi.org/10.1093/ajh/hpz150

Irvin, MR, Sitlani, CM, Floyd, JS, Psaty, BM, Bis, JC, Wiggins, KL, Whitsel, EA, Sturmer, T, Stewart, J, Raffield, L, Sun, F, Liu, C-T, Xu, H, Cupples, AL, Tanner, RM, Rossing, P, Smith, A, Zilhão, NR, Launer, LJ, Noordam, R, Rotter, JI, Yao, J, Li, X, Guo, X, Limdi, N, Sundaresan, A, Lange, L, Correa, A, Stott, DJ, Ford, I, Jukema, JW, Gudnason, V, Mook-Kanamori, DO, Trompet, S, Palmas, W, Warren, HR, Hellwege, JN, Giri, A, O'donnell, C, Hung, AM, Edwards, TL, Ahluwalia, TS, Arnett, DK & Avery, CL 2019, 'Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group', American Journal of Hypertension, bind 32, nr. 12, s. 1146-1153. https://doi.org/10.1093/ajh/hpz150

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

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.",

author = "Irvin, {Marguerite R} and Sitlani, {Colleen M} and Floyd, {James S} and Psaty, {Bruce M} and Bis, {Joshua C} and Wiggins, {Kerri L} and Whitsel, {Eric A} and Til Sturmer and James Stewart and Laura Raffield and Fangui Sun and Ching-Ti Liu and Hanfei Xu and Cupples, {Adrienne L} and Tanner, {Rikki M} and Peter Rossing and Albert Smith and Zilh{\~a}o, {Nuno R} and Launer, {Lenore J} and Raymond Noordam and Rotter, {Jerome I} and Jie Yao and Xiaohui Li and Xiuqing Guo and Nita Limdi and Aishwarya Sundaresan and Leslie Lange and Adolfo Correa and Stott, {David J} and Ian Ford and Jukema, {J Wouter} and Vilmundur Gudnason and Mook-Kanamori, {Dennis O} and Stella Trompet and Walter Palmas and Warren, {Helen R} and Hellwege, {Jacklyn N} and Ayush Giri and Christopher O'donnell and Hung, {Adriana M} and Edwards, {Todd L} and Ahluwalia, {Tarunveer S.} and Arnett, {Donna K} and Avery, {Christy L}",

year = "2019",

doi = "10.1093/ajh/hpz150",

language = "English",

volume = "32",

pages = "1146--1153",

journal = "American Journal of Hypertension",

issn = "0895-7061",

publisher = "Oxford University Press",

number = "12",

}

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 - Jukema, J Wouter

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

PY - 2019

Y1 - 2019

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.

U2 - 10.1093/ajh/hpz150

DO - 10.1093/ajh/hpz150

M3 - Journal article

C2 - 31545351

SN - 0895-7061

VL - 32

SP - 1146

EP - 1153

JO - American Journal of Hypertension

JF - American Journal of Hypertension

IS - 12

ER -