Pharmacogenomics Study of Thiazide Diuretics and QT Interval in Multi-Ethnic Populations: The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)
- Seyerle, Amanda A
- Sitlani, Colleen M
- Noordam, Raymond
- Gogarten, Stephanie M
- Li, Jin
- Li, Xiaohui
- Evans, Daniel S
- Sun, Fangui
- Laaksonen, Maarit A
- Isaacs, Aaron
- Kristiansson, Kati
- Highland, Heather M
- Stewart, James D
- Harris, Tamara B
- Trompet, Stella
- Bis, Joshua C
- Peloso, Gina M
- Brody, Jennifer A
- Broer, Linda
- Busch, Evan L
- Duan, Qing
- Stilp, Adrienne M
- O’Donnell, Christopher J
- Macfarlane, Peter W
- Floyd, James S
- Kors, Jan A
- Lin, Henry J
- Li-Gao, Ruifang
- Sofer, Tamar
- Méndez-Giráldez, Raúl
- Cummings, Steven R
- Heckbert, Susan R
- Hofman, Albert
- Ford, Ian
- Li, Yun
- Launer, Lenore J
- Porthan, Kimmo
- Newton-Cheh, Christopher
- Napier, Melanie D
- Kerr, Kathleen F
- Reiner, Alexander P
- Rice, Kenneth M
- Roach, Jeffrey
- Buckley, Brendan M
- Soliman, Elsayed Z
- de Mutsert, Renée
- Sotoodehnia, Nona
- Uitterlinden, André G
- North, Kari E
- Lee, Craig R
- Gudnason, Vilmundur
- Stürmer, Til
- Rosendaal, Frits R
- Taylor, Kent D
- Wiggins, Kerri L
- Wilson, James G
- Chen, Yii-Der I
- Kaplan, Robert C
- Wilhelmsen, Kirk
- Cupples, L Adrienne
- Salomaa, Veikko
- van Duijn, Cornelia
- Jukema, J Wouter
- Liu, Yongmei
- Mook-Kanamori, Dennis O
- Lange, Leslie A
- Vasan, Ramachandran S
- Smith, Albert V
- Stricker, Bruno H
- Laurie, Cathy C
- Rotter, Jerome I
- Whitsel, Eric A
- Psaty, Bruce M
- Avery, Christy L
DOIAbstract
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 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...
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