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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.
Thursday,2017-10-26 15:42 America/Los_Angeles — ecterry
| Title | Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | 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, DI Chen, Y-, 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 |
| Journal | Pharmacogenomics J |
| Date Published | 2017 Jul 18 |
| ISSN | 1473-1150 |
| Abstract | <p>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.The Pharmacogenomics Journal advance online publication, 18 July 2017; doi:10.1038/tpj.2017.10.</p> |
| DOI | 10.1038/tpj.2017.10 |
| Alternate Journal | Pharmacogenomics J. |
| PubMed ID | 28719597 |
| Grant List | UL1 RR033176 / RR / NCRR NIH HHS / United States R00 HL098458 / HL / NHLBI NIH HHS / United States R01 HL103612 / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 ES017794 / ES / NIEHS NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States N01 HC095161 / HC / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States UL1 RR024156 / RR / NCRR NIH HHS / United States N01 HC095164 / HC / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01 HC095166 / HC / NHLBI NIH HHS / United States N01 HC065237 / HC / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01 AG062106 / AG / NIA NIH HHS / United States N01 HC095160 / HC / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268200782096C / HG / NHGRI NIH HHS / United States T32 HL007779 / HL / NHLBI NIH HHS / United States N01 HC065236 / HC / NHLBI NIH HHS / United States N01 HC095165 / HC / NHLBI NIH HHS / United States N01 HC065235 / HC / NHLBI NIH HHS / United States N01 HC095163 / HC / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States U01 HG005152 / HG / NHGRI NIH HHS / United States T32 HL007055 / HL / NHLBI NIH HHS / United States K23 HL080025 / HL / NHLBI NIH HHS / United States R01 HL111089 / HL / NHLBI NIH HHS / United States R01 HL116747 / HL / NHLBI NIH HHS / United States N01 HC095159 / HC / NHLBI NIH HHS / United States |
ePub date:
17/07