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Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.

Publication ,  Journal Article
Seyerle, AA; Sitlani, CM; Noordam, R; Gogarten, SM; Li, J; Li, X; Evans, DS; Sun, F; Laaksonen, MA; Isaacs, A; Kristiansson, K; Highland, HM ...
Published in: Pharmacogenomics J
April 2018

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.

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Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

April 2018

Volume

18

Issue

2

Start / End Page

215 / 226

Location

United States

Related Subject Headings

  • Sodium Chloride Symporter Inhibitors
  • Polymorphism, Single Nucleotide
  • Pharmacology & Pharmacy
  • Pharmacogenetics
  • Middle Aged
  • Male
  • Longitudinal Studies
  • Humans
  • Heart Rate
  • Genomics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Seyerle, A. A., Sitlani, C. M., Noordam, R., Gogarten, S. M., Li, J., Li, X., … Avery, C. L. (2018). Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology. Pharmacogenomics J, 18(2), 215–226. https://doi.org/10.1038/tpj.2017.10
Seyerle, A. A., C. M. Sitlani, R. Noordam, S. M. Gogarten, J. Li, X. Li, D. S. Evans, et al. “Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.Pharmacogenomics J 18, no. 2 (April 2018): 215–26. https://doi.org/10.1038/tpj.2017.10.
Seyerle AA, Sitlani CM, Noordam R, Gogarten SM, Li J, Li X, et al. Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology. Pharmacogenomics J. 2018 Apr;18(2):215–26.
Seyerle, A. A., et al. “Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.Pharmacogenomics J, vol. 18, no. 2, Apr. 2018, pp. 215–26. Pubmed, doi:10.1038/tpj.2017.10.
Seyerle AA, Sitlani CM, Noordam R, Gogarten SM, Li J, Li X, Evans DS, Sun F, Laaksonen MA, Isaacs A, Kristiansson K, Highland HM, Stewart JD, Harris TB, Trompet S, Bis JC, Peloso GM, Brody JA, Broer L, Busch EL, Duan Q, Stilp AM, O’Donnell CJ, Macfarlane PW, Floyd JS, Kors JA, Lin HJ, Li-Gao R, Sofer T, Méndez-Giráldez R, Cummings SR, Heckbert SR, Hofman A, Ford I, Li Y, Launer LJ, Porthan K, Newton-Cheh C, Napier MD, Kerr KF, Reiner AP, Rice KM, Roach J, Buckley BM, Soliman EZ, de Mutsert R, Sotoodehnia N, Uitterlinden AG, North KE, Lee CR, Gudnason V, Stürmer T, Rosendaal FR, Taylor KD, Wiggins KL, Wilson JG, Chen Y-D, Kaplan RC, Wilhelmsen K, Cupples LA, Salomaa V, van Duijn C, Jukema JW, Liu Y, Mook-Kanamori DO, Lange LA, Vasan RS, Smith AV, Stricker BH, Laurie CC, Rotter JI, Whitsel EA, Psaty BM, Avery CL. Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology. Pharmacogenomics J. 2018 Apr;18(2):215–226.

Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

April 2018

Volume

18

Issue

2

Start / End Page

215 / 226

Location

United States

Related Subject Headings

  • Sodium Chloride Symporter Inhibitors
  • Polymorphism, Single Nucleotide
  • Pharmacology & Pharmacy
  • Pharmacogenetics
  • Middle Aged
  • Male
  • Longitudinal Studies
  • Humans
  • Heart Rate
  • Genomics