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, Robert 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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.The Pharmacogenomics Journal advance online publication, 13 December 2016; doi:10.1038/tpj.2016.90.

Original languageEnglish (US)
JournalPharmacogenomics Journal
DOIs
StateAccepted/In press - Dec 13 2016

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Pharmacogenetics
Hispanic Americans
Electrocardiography
Phenotype
Genome-Wide Association Study
Drug-Related Side Effects and Adverse Reactions
African Americans
Type 2 Diabetes Mellitus
Publications
Meta-Analysis
Cardiovascular Diseases
Pharmacokinetics
Genome
Research
Pharmacogenomic Testing
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Floyd, J. S., Sitlani, C. M., Avery, C. L., Noordam, R., Li, X., Smith, A. V., ... Stricker, B. H. (Accepted/In press). Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group. Pharmacogenomics Journal. https://doi.org/10.1038/tpj.2016.90

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals : CHARGE Pharmacogenomics Working Group. / 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.; Harris, T. B.; Li-Gao, R.; Sattar, N.; Cummings, S. R.; Wiggins, K. L.; Napier, M. D.; Stürmer, T.; Bis, J. C.; Kerr, K. F.; Uitterlinden, A. G.; Taylor, K. D.; Stott, D. J.; de Mutsert, R.; Launer, L. J.; Busch, E. L.; Méndez-Giráldez, R.; Sotoodehnia, N.; Soliman, E. Z.; Li, Y.; Duan, Q.; Rosendaal, F. R.; Slagboom, P. E.; Wilhelmsen, K. C.; Reiner, A. P.; Chen, Y. DI; Heckbert, S. R.; Kaplan, Robert C.; Rice, K. M.; Jukema, J. W.; Johnson, A. D.; Liu, Y.; Mook-Kanamori, D. O.; Gudnason, V.; Wilson, J. G.; Rotter, J. I.; Laurie, C. C.; Psaty, B. M.; Whitsel, E. A.; Cupples, L. A.; Stricker, B. H.

In: Pharmacogenomics Journal, 13.12.2016.

Research output: Contribution to journalArticle

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, YDI, 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 2016, 'Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group', Pharmacogenomics Journal. https://doi.org/10.1038/tpj.2016.90
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. ; Harris, T. B. ; Li-Gao, R. ; Sattar, N. ; Cummings, S. R. ; Wiggins, K. L. ; Napier, M. D. ; Stürmer, T. ; Bis, J. C. ; Kerr, K. F. ; Uitterlinden, A. G. ; Taylor, K. D. ; Stott, D. J. ; de Mutsert, R. ; Launer, L. J. ; Busch, E. L. ; Méndez-Giráldez, R. ; Sotoodehnia, N. ; Soliman, E. Z. ; Li, Y. ; Duan, Q. ; Rosendaal, F. R. ; Slagboom, P. E. ; Wilhelmsen, K. C. ; Reiner, A. P. ; Chen, Y. DI ; Heckbert, S. R. ; Kaplan, Robert C. ; Rice, K. M. ; Jukema, J. W. ; Johnson, A. D. ; Liu, Y. ; Mook-Kanamori, D. O. ; Gudnason, V. ; Wilson, J. G. ; Rotter, J. I. ; Laurie, C. C. ; Psaty, B. M. ; Whitsel, E. A. ; Cupples, L. A. ; Stricker, B. H. / Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals : CHARGE Pharmacogenomics Working Group. In: Pharmacogenomics Journal. 2016.
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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.The Pharmacogenomics Journal advance online publication, 13 December 2016; doi:10.1038/tpj.2016.90.",
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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, Robert 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 - 2016/12/13

Y1 - 2016/12/13

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.The Pharmacogenomics Journal advance online publication, 13 December 2016; doi:10.1038/tpj.2016.90.

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.The Pharmacogenomics Journal advance online publication, 13 December 2016; doi:10.1038/tpj.2016.90.

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U2 - 10.1038/tpj.2016.90

DO - 10.1038/tpj.2016.90

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