1. Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology
- Author
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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-DI, 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, and Avery, CL
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Genetics ,Cardiovascular ,Human Genome ,Adult ,Aged ,Aged ,80 and over ,Aging ,Cohort Studies ,Electrocardiography ,Ethnicity ,Female ,Genomics ,Heart Rate ,Humans ,Longitudinal Studies ,Male ,Middle Aged ,Pharmacogenetics ,Polymorphism ,Single Nucleotide ,Sodium Chloride Symporter Inhibitors ,Pharmacology & Pharmacy ,Pharmacology and pharmaceutical sciences - Abstract
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
- Published
- 2018