Seyerle, Amanda ASitlani, Colleen MNoordam, RaymondGogarten, Stephanie MLi, JinLi, XiaohuiEvans, Daniel SSun, FanguiLaaksonen, Maarit AIsaacs, AaronKristiansson, KatiHighland, Heather MStewart, James DHarris, Tamara BTrompet, StellaBis, Joshua CPeloso, Gina MBrody, Jennifer ABroer, LindaBusch, EvanDuan, QingStilp, Adrienne MO’Donnell, Christopher JMacfarlane, Peter WFloyd, James SKors, Jan ALin, Henry JLi-Gao, RuifangSofer, TamarMéndez-Giráldez, RaúlCummings, Steven RHeckbert, Susan RHofman, AlbertFord, IanLi, YunLauner, Lenore JPorthan, KimmoNewton-Cheh, ChristopherNapier, Melanie DKerr, Kathleen FReiner, Alexander PRice, Kenneth MRoach, JeffreyBuckley, Brendan MSoliman, Elsayed Zde Mutsert, RenéeSotoodehnia, NonaUitterlinden, André GNorth, Kari ELee, Craig RGudnason, VilmundurStürmer, TilRosendaal, Frits RTaylor, Kent DWiggins, Kerri LWilson, James GChen, Yii-Der IKaplan, Robert CWilhelmsen, KirkCupples, L AdrienneSalomaa, Veikkovan Duijn, CorneliaJukema, J WouterLiu, YongmeiMook-Kanamori, Dennis OLange, Leslie AVasan, Ramachandran SSmith, Albert VStricker, Bruno HLaurie, Cathy CRotter, Jerome IWhitsel, Eric APsaty, Bruce MAvery, Christy L2018-02-262017Seyerle, A. A., C. M. Sitlani, R. Noordam, S. M. Gogarten, J. Li, X. Li, D. S. Evans, et al. 2017. “Pharmacogenomics Study of Thiazide Diuretics and QT Interval in Multi-Ethnic Populations: The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE).” The pharmacogenomics journal :10.1038/tpj.2017.10. doi:10.1038/tpj.2017.10. http://dx.doi.org/10.1038/tpj.2017.10.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34868972Thiazide 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 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 (e.g. 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.en-USJournal Article2018-02-2610.1038/tpj.2017.10