Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

J. S. Floyd; C. M. Sitlani; C. L. Avery; R. Noordam; X. Li; A. V. Smith; S. M. Gogarten; J. Li; L. Broer; D. S. Evans; S. Trompet; J. A. Brody; J. D. Stewart; J. D. Eicher; A. A. Seyerle; J. Roach; L. A. Lange; H. J. Lin; J. A. Kors; T. B. Harris; R. Li-Gao; N. Sattar; S. R. Cummings; K. L. Wiggins; M. D. Napier; T. Stürmer; J. C. Bis; K. F. Kerr; A. G. Uitterlinden; K. D. Taylor; D. J. Stott; R. De Mutsert; L. J. Launer; E. L. Busch; R. Méndez-Giráldez; N. Sotoodehnia; E. Z. Soliman; Y. Li; Q. Duan; F. R. Rosendaal; P. E. Slagboom; K. C. Wilhelmsen; A. P. Reiner; Y. Di Chen; S. R. Heckbert; R. C. Kaplan; K. M. Rice; J. W. Jukema; A. D. Johnson; Y. Liu; D. O. Mook-Kanamori; V. Gudnason; J. G. Wilson; J. I. Rotter; C. C. Laurie; B. M. Psaty; E. A. Whitsel; L. A. Cupples; B. H. Stricker

doi:10.1038/tpj.2016.90

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

J. S. Floyd, C. M. Sitlani, C. L. Avery, R. Noordam, X. Li, A. V. Smith, S. M. Gogarten, J. Li, L. Broer, D. S. Evans, S. Trompet, J. A. Brody, J. D. Stewart, J. D. Eicher, A. A. Seyerle, J. Roach, L. A. Lange, H. J. Lin, J. A. Kors, T. B. HarrisR. Li-Gao, N. Sattar, S. R. Cummings, K. L. Wiggins, M. D. Napier, T. Stürmer, J. C. Bis, K. F. Kerr, A. G. Uitterlinden, K. D. Taylor, D. J. Stott, R. De Mutsert, L. J. Launer, E. L. Busch, R. Méndez-Giráldez, N. Sotoodehnia, E. Z. Soliman, Y. Li, Q. Duan, F. R. Rosendaal, P. E. Slagboom, K. C. Wilhelmsen, A. P. Reiner, Y. Di Chen, S. R. Heckbert, R. C. Kaplan, K. M. Rice, J. W. Jukema, A. D. Johnson, Y. Liu, D. O. Mook-Kanamori, V. Gudnason, J. G. Wilson, J. I. Rotter, C. C. Laurie, B. M. Psaty, E. A. Whitsel, L. A. Cupples, B. H. Stricker

Epidemiology & Population Health

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10 ' '8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.

Original language	English (US)
Pages (from-to)	127-135
Number of pages	9
Journal	Pharmacogenomics Journal
Volume	18
Issue number	1
DOIs	https://doi.org/10.1038/tpj.2016.90
State	Published - Jan 1 2018

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/tpj.2016.90

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Floyd, J. S., Sitlani, C. M., Avery, C. L., Noordam, R., Li, X., Smith, A. V., Gogarten, S. M., Li, J., Broer, L., Evans, D. S., Trompet, S., Brody, J. A., Stewart, J. D., Eicher, J. D., Seyerle, A. A., Roach, J., Lange, L. A., Lin, H. J., Kors, J. A., ... Stricker, B. H. (2018). Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group. Pharmacogenomics Journal, 18(1), 127-135. https://doi.org/10.1038/tpj.2016.90

Floyd, JS, Sitlani, CM, Avery, CL, Noordam, R, Li, X, Smith, AV, Gogarten, SM, Li, J, Broer, L, Evans, DS, Trompet, S, Brody, JA, Stewart, JD, Eicher, JD, Seyerle, AA, Roach, J, Lange, LA, Lin, HJ, Kors, JA, Harris, TB, Li-Gao, R, Sattar, N, Cummings, SR, Wiggins, KL, Napier, MD, Stürmer, T, Bis, JC, Kerr, KF, Uitterlinden, AG, Taylor, KD, Stott, DJ, De Mutsert, R, Launer, LJ, Busch, EL, Méndez-Giráldez, R, Sotoodehnia, N, Soliman, EZ, Li, Y, Duan, Q, Rosendaal, FR, Slagboom, PE, Wilhelmsen, KC, Reiner, AP, Chen, YD, Heckbert, SR, Kaplan, RC, Rice, KM, Jukema, JW, Johnson, AD, Liu, Y, Mook-Kanamori, DO, Gudnason, V, Wilson, JG, Rotter, JI, Laurie, CC, Psaty, BM, Whitsel, EA, Cupples, LA & Stricker, BH 2018, 'Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group', Pharmacogenomics Journal, vol. 18, no. 1, pp. 127-135. https://doi.org/10.1038/tpj.2016.90

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title = "Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group",

abstract = "Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10 ' '8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.",

author = "Floyd, {J. S.} and Sitlani, {C. M.} and Avery, {C. L.} and R. Noordam and X. Li and Smith, {A. V.} and Gogarten, {S. M.} and J. Li and L. Broer and Evans, {D. S.} and S. Trompet and Brody, {J. A.} and Stewart, {J. D.} and Eicher, {J. D.} and Seyerle, {A. A.} and J. Roach and Lange, {L. A.} and Lin, {H. J.} and Kors, {J. A.} and Harris, {T. B.} and R. Li-Gao and N. Sattar and Cummings, {S. R.} and Wiggins, {K. L.} and Napier, {M. D.} and T. St{\"u}rmer and Bis, {J. C.} and Kerr, {K. F.} and Uitterlinden, {A. G.} and Taylor, {K. D.} and Stott, {D. J.} and {De Mutsert}, R. and Launer, {L. J.} and Busch, {E. L.} and R. M{\'e}ndez-Gir{\'a}ldez and N. Sotoodehnia and Soliman, {E. Z.} and Y. Li and Q. Duan and Rosendaal, {F. R.} and Slagboom, {P. E.} and Wilhelmsen, {K. C.} and Reiner, {A. P.} and Chen, {Y. Di} and Heckbert, {S. R.} and Kaplan, {R. C.} and Rice, {K. M.} and Jukema, {J. W.} and Johnson, {A. D.} and Y. Liu and Mook-Kanamori, {D. O.} and V. Gudnason and Wilson, {J. G.} and Rotter, {J. I.} and Laurie, {C. C.} and Psaty, {B. M.} and Whitsel, {E. A.} and Cupples, {L. A.} and Stricker, {B. H.}",

year = "2018",

month = jan,

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doi = "10.1038/tpj.2016.90",

language = "English (US)",

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T1 - Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals

T2 - CHARGE Pharmacogenomics Working Group

AU - Floyd, J. S.

AU - Sitlani, C. M.

AU - Avery, C. L.

AU - Noordam, R.

AU - Li, X.

AU - Smith, A. V.

AU - Gogarten, S. M.

AU - Li, J.

AU - Broer, L.

AU - Evans, D. S.

AU - Trompet, S.

AU - Brody, J. A.

AU - Stewart, J. D.

AU - Eicher, J. D.

AU - Seyerle, A. A.

AU - Roach, J.

AU - Lange, L. A.

AU - Lin, H. J.

AU - Kors, J. A.

AU - Harris, T. B.

AU - Li-Gao, R.

AU - Sattar, N.

AU - Cummings, S. R.

AU - Wiggins, K. L.

AU - Napier, M. D.

AU - Stürmer, T.

AU - Bis, J. C.

AU - Kerr, K. F.

AU - Uitterlinden, A. G.

AU - Taylor, K. D.

AU - Stott, D. J.

AU - De Mutsert, R.

AU - Launer, L. J.

AU - Busch, E. L.

AU - Méndez-Giráldez, R.

AU - Sotoodehnia, N.

AU - Soliman, E. Z.

AU - Li, Y.

AU - Duan, Q.

AU - Rosendaal, F. R.

AU - Slagboom, P. E.

AU - Wilhelmsen, K. C.

AU - Reiner, A. P.

AU - Chen, Y. Di

AU - Heckbert, S. R.

AU - Kaplan, R. C.

AU - Rice, K. M.

AU - Jukema, J. W.

AU - Johnson, A. D.

AU - Liu, Y.

AU - Mook-Kanamori, D. O.

AU - Gudnason, V.

AU - Wilson, J. G.

AU - Rotter, J. I.

AU - Laurie, C. C.

AU - Psaty, B. M.

AU - Whitsel, E. A.

AU - Cupples, L. A.

AU - Stricker, B. H.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10 ' '8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.

AB - Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10 ' '8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.

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U2 - 10.1038/tpj.2016.90

DO - 10.1038/tpj.2016.90

M3 - Article

C2 - 27958378

AN - SCOPUS:85004008377

SN - 1470-269X

VL - 18

SP - 127

EP - 135

JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

IS - 1

ER -

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Abstract

ASJC Scopus subject areas

UN SDGs

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