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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C M van Duijn, James S. Floyd, Maarit A. Laaksonen, André G. Uitterlinden, Colleen M. Sitlani, Y-Di Chen, H J Lin, Christopher Newton-Cheh, Kent D. Taylor, Albert V. Smith, Til Stürmer, Kari E. North, Peter W. Macfarlane, Dennis O. Mook-Kanamori, Raymond Noordam, Yun Li, Jun Li, Tamar Sofer, Raul Mendez-Giraldez, Adrienne M. Stilp, Cathy C. Laurie, Ian Ford, Christy L. Avery, Stella Trompet, Nona Sotoodehnia, Jeffrey Roach, T.B. Harris, Jennifer A. Brody, Susan R. Heckbert, L. A. Cupples, J. C. Bis, Ruifang Li-Gao, Christopher J. O'Donnell, Vilmundur Gudnason, Robert C. Kaplan, Brendan M. Buckley, R. de Mutsert, Jan A. Kors, Steve Cummings, Elsayed Z. Soliman, Xiaohui Li, Kati Kristiansson, Linda Broer, Alexander P. Reiner, Joop Jukema, Aaron Isaacs, Evan L. Busch, Craig R. Lee, Amanda A. Seyerle, Heather M. Highland, Kathleen F. Kerr, Bruce M. Psaty, Leslie A. Lange, Qing Duan, Veikko Salomaa, Kenneth Rice, James D. Stewart, Stephanie M. Gogarten, E. A. Whitsel, Kirk C. Wilhelmsen, Daniel S. Evans, Yongmei Liu, Bruno H. Stricker, Fangui Sun, Kimmo Porthan, A. Hofman, Gina M. Peloso, L. J. Launer, Kerri L. Wiggins, Melanie D. Napier, Jerome I. Rotter, Frits R. Rosendaal, James G. Wilson, Ramachandran S. Vasan, Kardiologian yksikkö, Department of Medicine, Clinicum, Genetica & Celbiologie, Biochemie, RS: CARIM - R1.01 - Blood proteins & engineering, RS: CARIM - R1.06 - Genetic Epidemiology and Genomics of cardiovascular diseases, RS: FHML MaCSBio, Epidemiology, Internal Medicine, Medical Informatics, and Erasmus MC other
- Subjects
Male ,0301 basic medicine ,Influencing antihypertensive response ,Aging ,Sodium Chloride Symporter Inhibitors ,Blood-pressure response ,Gene-environment interactions ,Ethnic populations ,VARIANTS ,Cardiovascular ,Bioinformatics ,Cohort Studies ,Electrocardiography ,Cardiovascular drugs ,Heart Rate ,Polymorphism (computer science) ,HYPERTENSIVE PATIENTS ,Epidemiology ,80 and over ,Ethnicity ,WIDE ASSOCIATION ,Pharmacology & Pharmacy ,Longitudinal Studies ,Aged, 80 and over ,Wide association ,Genomewide association ,Variants ,Single Nucleotide ,Pharmacology and Pharmaceutical Sciences ,Genomics ,Middle Aged ,CARDIOVASCULAR DRUGS ,3. Good health ,317 Pharmacy ,Molecular Medicine ,Female ,Cohort study ,medicine.drug ,Adult ,medicine.medical_specialty ,INFLUENCING ANTIHYPERTENSIVE RESPONSE ,MEDLINE ,UNITED-STATES ,Polymorphism, Single Nucleotide ,QT interval ,Article ,03 medical and health sciences ,BLOOD-PRESSURE RESPONSE ,Genetics ,medicine ,Humans ,Polymorphism ,Thiazide ,Hypertensive patients ,Aged ,Pharmacology ,Selection bias ,SELECTION BIAS ,business.industry ,Human Genome ,R1 ,GENE-ENVIRONMENT INTERACTIONS ,United States ,030104 developmental biology ,Pharmacogenetics ,Pharmacogenomics ,GENOMEWIDE ASSOCIATION ,business - 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, transethnic 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