Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-07-18

AUTHORS

A A Seyerle, C M Sitlani, R Noordam, S M Gogarten, J Li, X Li, D S Evans, F Sun, M A Laaksonen, A Isaacs, K Kristiansson, H M Highland, J D Stewart, T B Harris, S Trompet, J C Bis, G M Peloso, J A Brody, L Broer, E L Busch, Q Duan, A M Stilp, C J O'Donnell, P W Macfarlane, J S Floyd, J A Kors, H J Lin, R Li-Gao, T Sofer, R Méndez-Giráldez, S R Cummings, S R Heckbert, A Hofman, I Ford, Y Li, L J Launer, K Porthan, C Newton-Cheh, M D Napier, K F Kerr, A P Reiner, K M Rice, J Roach, B M Buckley, E Z Soliman, R de Mutsert, N Sotoodehnia, A G Uitterlinden, K E North, C R Lee, V Gudnason, T Stürmer, F R Rosendaal, K D Taylor, K L Wiggins, J G Wilson, Y-DI Chen, R C Kaplan, K Wilhelmsen, L A Cupples, V Salomaa, C van Duijn, J W Jukema, Y Liu, D O Mook-Kanamori, L A Lange, R S Vasan, A V Smith, B H Stricker, C C Laurie, J I Rotter, E A Whitsel, B M Psaty, C L Avery

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, 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. More... »

PAGES

215-226

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  • Journal

    TITLE

    The Pharmacogenomics Journal

    ISSUE

    2

    VOLUME

    18

    Author Affiliations

  • Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA
  • Department of Medicine, University of Washington, Seattle, WA, USA
  • Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
  • Department of Biostatistics, University of Washington, Seattle, WA, USA
  • Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA
  • Department of Pediatrics, Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
  • California Pacific Medical Center Research Institute, San Francisco, CA, USA
  • Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Department of Health, THL-National Institute for Health and Welfare, Helsinki, Finland
  • and Department of Biochemistry, CARIM School of Cardiovascular Diseases, Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands
  • Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
  • Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA
  • Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA
  • Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
  • Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  • Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
  • Cardiology Section, Boston Veterans Administration Healthcare, Boston, MA, USA
  • Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
  • Department of Epidemiology, University of Washington, Seattle, WA, USA
  • Department of Medical Informatics, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Division of Medical Genetics, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA
  • Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  • Department of Epidemiology, Erasmus MC—University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK
  • Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA
  • Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland
  • Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
  • Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • Research Computing Center, University of North Carolina, Chapel Hill, NC, USA
  • Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland
  • Epidemiology Cardiology Research Center (EPICARE), Wake Forest School of Medicine, Winston-Salem, NC, USA
  • Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA
  • Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
  • Department of Medicine, University of Iceland, Reykjavik, Iceland
  • Center for Pharmacoepidemiology, University of North Carolina, Chapel Hill, NC, USA
  • Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA
  • Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
  • The Renaissance Computing Institute, Chapel Hill, NC, USA
  • National Heart, Lung, and Blood Institute Framingham Heart Study, Framingham, MA, USA
  • Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
  • Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University, Winston-Salem, NC, USA
  • Department of BESC, Epidemiology Section, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
  • Division of Preventive Medicine and Epidemiology, Department of Epidemiology, Boston University School of Medicine, Boston, MA, USA
  • Inspectorate of Health Care, Utrecht, The Netherlands
  • Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
  • Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/tpj.2017.10

    DOI

    http://dx.doi.org/10.1038/tpj.2017.10

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1090745769

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28719597


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