PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Jessica van Setten, Jennifer A. Brody, Yalda Jamshidi, Brenton R. Swenson, Anne M. Butler, Harry Campbell, Fabiola M. Del Greco, Daniel S. Evans, Quince Gibson, Daniel F. Gudbjartsson, Kathleen F. Kerr, Bouwe P. Krijthe, Leo-Pekka Lyytikäinen, Christian Müller, Martina Müller-Nurasyid, Ilja M. Nolte, Sandosh Padmanabhan, Marylyn D. Ritchie, Antonietta Robino, Albert V. Smith, Maristella Steri, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sheila Ulivi, Niek Verweij, Xiaoyan Yin, David O. Arnar, Folkert W. Asselbergs, Joel S. Bader, John Barnard, Josh Bis, Stefan Blankenberg, Eric Boerwinkle, Yuki Bradford, Brendan M. Buckley, Mina K. Chung, Dana Crawford, Marcel den Hoed, Josh C. Denny, Anna F. Dominiczak, Georg B. Ehret, Mark Eijgelsheim, Patrick T. Ellinor, Stephan B. Felix, Oscar H. Franco, Lude Franke, Tamara B. Harris, Hilma Holm, Gandin Ilaria, Annamaria Iorio, Mika Kähönen, Ivana Kolcic, Jan A. Kors, Edward G. Lakatta, Lenore J. Launer, Honghuang Lin, Henry J. Lin, Ruth J. F. Loos, Steven A. Lubitz, Peter W. Macfarlane, Jared W. Magnani, Irene Mateo Leach, Thomas Meitinger, Braxton D. Mitchell, Thomas Munzel, George J. Papanicolaou, Annette Peters, Arne Pfeufer, Peter P. Pramstaller, Olli T. Raitakari, Jerome I. Rotter, Igor Rudan, Nilesh J. Samani, David Schlessinger, Claudia T. Silva Aldana, Moritz F. Sinner, Jonathan D. Smith, Harold Snieder, Elsayed Z. Soliman, Timothy D. Spector, David J. Stott, Konstantin Strauch, Kirill V. Tarasov, Unnur Thorsteinsdottir, Andre G. Uitterlinden, David R. Van Wagoner, Uwe Völker, Henry Völzke, Melanie Waldenberger, Harm Jan Westra, Philipp S. Wild, Tanja Zeller, Alvaro Alonso, Christy L. Avery, Stefania Bandinelli, Emelia J. Benjamin, Francesco Cucca, Marcus Dörr, Luigi Ferrucci, Paolo Gasparini, Vilmundur Gudnason, Caroline Hayward, Susan R. Heckbert, Andrew A. Hicks, J. Wouter Jukema, Stefan Kääb, Terho Lehtimäki, Yongmei Liu, Patricia B. Munroe, Afshin Parsa, Ozren Polasek, Bruce M. Psaty, Dan M. Roden, Renate B. Schnabel, Gianfranco Sinagra, Kari Stefansson, Bruno H. Stricker, Pim van der Harst, Cornelia M. van Duijn, James F. Wilson, Sina A. Gharib, Paul I. W. de Bakker, Aaron Isaacs, Dan E. Arking, Nona Sotoodehnia

ABSTRACT

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development. More... »

PAGES

2904

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

9

Author Affiliations

  • University of Washington
  • St George's, University of London
  • Washington University in St. Louis
  • University of Edinburgh
  • California Pacific Medical Center
  • University of Alabama at Birmingham Hospital
  • University of Iceland
  • Erasmus University Medical Center
  • University of Tampere
  • German Centre for Cardiovascular Research
  • University Medical Center Groningen
  • University of Glasgow
  • University of Pennsylvania
  • IRCCS Materno Infantile Burlo Garofolo
  • University of Michigan–Ann Arbor
  • Institute of Genetic and Biomedical Research
  • Leiden University Medical Center
  • Boston University School of Medicine
  • National University Hospital of Iceland
  • University College London
  • Johns Hopkins University
  • Cleveland Clinic
  • The University of Texas Health Science Center at Houston
  • University College Cork
  • Case Western Reserve University
  • Uppsala University
  • Vanderbilt University
  • Massachusetts General Hospital
  • University of Greifswald
  • National Institutes of Health
  • University of Trieste
  • University of Split
  • Harbor–UCLA Medical Center
  • Icahn School of Medicine at Mount Sinai
  • University of Pittsburgh
  • University of Maryland, Baltimore
  • University Medical Center of the Johannes Gutenberg University Mainz
  • National Heart Lung and Blood Institute
  • German Center for Diabetes Research
  • University of Turku
  • University of Leicester
  • National Institute of Child Health and Human Development
  • Del Rosario University
  • Wake Forest University
  • King's College London
  • Ludwig Maximilian University of Munich
  • Emory University
  • University of North Carolina at Chapel Hill
  • Azienda Sanitaria di Firenze
  • Netherlands Heart Institute
  • National Institute for Health Research
  • Kaiser Permanente Washington Health Research Institute
  • University Medical Center Utrecht
  • Maastricht University
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-04766-9

    DOI

    http://dx.doi.org/10.1038/s41467-018-04766-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1105714095

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30046033


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