دورية أكاديمية
Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.
| العنوان: | Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology. |
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| المؤلفون: | Seyerle, A A, Sitlani, C M, Noordam, R, Gogarten, S M, Li, J, Li, X, Evans, D S, Sun, F, Laaksonen, M A, Isaacs, A, Kristiansson, K, Highland, H M, Stewart, J D, Harris, T B, Trompet, S, Bis, J C, Peloso, G M, Brody, J A, Broer, L, Busch, E L, Duan, Q, Stilp, A M, O'Donnell, C J, Macfarlane, P W, Floyd, J S, Kors, J A, Lin, H J, Li-Gao, R, Sofer, T, Méndez-Giráldez, R, Cummings, S R, Heckbert, S R, Hofman, A, Ford, I, Li, Y, Launer, L J, Porthan, K, Newton-Cheh, C, Napier, M D, Kerr, K F, Reiner, A P, Rice, K M, Roach, J, Buckley, B M, Soliman, E Z, de Mutsert, R, Sotoodehnia, N, Uitterlinden, A G, North, K E, Lee, C R, Gudnason, V, Stürmer, T, Rosendaal, F R, Taylor, K D, Wiggins, K L, Wilson, J G, Chen, Y-Di, Kaplan, R C, Wilhelmsen, K, Cupples, L A, Salomaa, V, van Duijn, C, Jukema, J W, Liu, Y, Mook-Kanamori, D O, Lange, L A, Vasan, R S, Smith, A V, Stricker, B H, Laurie, C C, Rotter, J I, Whitsel, E A, Psaty, B M, Avery, C L |
| المصدر: | Pharmacogenomics J ; ISSN:1473-1150 ; Volume:18 ; Issue:2 |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2018 |
| المجموعة: | PubMed Central (PMC) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1038/tpj.2017.10Test; https://pubmed.ncbi.nlm.nih.gov/28719597Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773415Test/ |
| DOI: | 10.1038/tpj.2017.10 |
| الإتاحة: | https://doi.org/10.1038/tpj.2017.10Test https://pubmed.ncbi.nlm.nih.gov/28719597Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773415Test/ |
| رقم الانضمام: | edsbas.24DB9E9D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/tpj.2017.10 |
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