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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.
van Setten, Jessica; Brody, Jennifer A; Jamshidi, Yalda; Swenson, Brenton R; Butler, Anne M; Campbell, Harry; Del Greco, Fabiola M; Evans, Daniel S; Gibson, Quince; Gudbjartsson, Daniel F; Kerr, Kathleen F; Krijthe, Bouwe P; Lyytikäinen, Leo-Pekka; Müller, Christian; Müller-Nurasyid, Martina; Nolte, Ilja M; Padmanabhan, Sandosh; Ritchie, Marylyn D; Robino, Antonietta; Smith, Albert V; Steri, Maristella; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; Ulivi, Sheila; Verweij, Niek; Yin, Xiaoyan; Arnar, David O; Asselbergs, Folkert W; Bader, Joel S; Barnard, John; Bis, Josh; Blankenberg, Stefan; Boerwinkle, Eric; Bradford, Yuki; Buckley, Brendan M; Chung, Mina K; Crawford, Dana; den Hoed, Marcel; Denny, Josh C; Dominiczak, Anna F; Ehret, Georg B; Eijgelsheim, Mark; Ellinor, Patrick T; Felix, Stephan B; Franco, Oscar H; Franke, Lude; Harris, Tamara B; Holm, Hilma; Ilaria, Gandin.
Afiliación
  • van Setten J; Department of Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, 3584CX, The Netherlands. J.vanSetten@umcutrecht.nl.
  • Brody JA; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, 98195, WA, USA.
  • Jamshidi Y; Cardiogenetics Lab, Molecular and Clinical Sciences Research Institute, St George's University of London, London, SW17 0RE, UK.
  • Swenson BR; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, 98195, WA, USA.
  • Butler AM; Institute for Public Health Genetics, School of Public Health, University of Washington, Seattle, 98195, WA, USA.
  • Campbell H; Division of Infectious Diseases, Washington University School of Medicine, St. Louis, 63110, MO, USA.
  • Del Greco FM; Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9YL, UK.
  • Evans DS; Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, 39100, Italy.
  • Gibson Q; California Pacific Medical Center Research Institute, San Francisco, 94107, CA, USA.
  • Gudbjartsson DF; Department of Surgery, University of Alabama Birmingham Hospital, Birmingham, 35233, AL, USA.
  • Kerr KF; deCODE genetics/Amgen, Inc., Reykjavik, IS-101, Iceland.
  • Krijthe BP; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, 101, Iceland.
  • Lyytikäinen LP; Department of Biostatistics, School of Public Health, University of Washington, Seattle, 98195, WA, USA.
  • Müller C; Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015GD, The Netherlands.
  • Müller-Nurasyid M; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33520, Finland.
  • Nolte IM; Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
  • Padmanabhan S; Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, 20251, Germany.
  • Ritchie MD; DZHK (German Center for Cardiovascular Research) Partner Site, Hamburg/Kiel/Lübeck, Germany.
  • Robino A; Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, D-85764, Germany.
  • Smith AV; Department of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Munich, 81377, Germany.
  • Steri M; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, 80802, Germany.
  • Tanaka T; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9713GZ, The Netherlands.
  • Teumer A; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9713GZ, The Netherlands.
  • Trompet S; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, Scotland, UK.
  • Ulivi S; Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, PA, USA.
  • Verweij N; Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
  • Yin X; Icelandic Heart Association, Kopavogur, IS-201, Iceland.
  • Arnar DO; Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
  • Asselbergs FW; Department of Biostatistics, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Bader JS; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, 00185, Cagliari, Italy.
  • Barnard J; Translational Gerontology Branch, NIA, Baltimore, 20892, MD, USA.
  • Bis J; Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17489, Germany.
  • Blankenberg S; DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, 17475, Greifswald, Germany.
  • Boerwinkle E; Department of Cardiology, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
  • Bradford Y; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300RC, The Netherlands.
  • Buckley BM; Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, 34137, Italy.
  • Chung MK; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, 7913GZ, The Netherlands.
  • Crawford D; Department of Medicine, Boston University School of Medicine, Boston, 02118, MA, USA.
  • den Hoed M; deCODE genetics/Amgen, Inc., Reykjavik, IS-101, Iceland.
  • Denny JC; Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
  • Dominiczak AF; Department of Medicine, Landspitali University Hospital, Reykjavik, 101, Iceland.
  • Ehret GB; Department of Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, 3584CX, The Netherlands.
  • Eijgelsheim M; Durrer Center for Cardiogenetic Research, Netherlands Heart Institute, Utrecht, The Netherlands.
  • Ellinor PT; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, WC1E 6BT, UK.
  • Felix SB; Farr Institute of Health Informatics Research and Institute of Health Informatics, University College London, London, WC1E 6BT, London, United Kingdom.
  • Franco OH; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, 21218, MD, USA.
  • Franke L; Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, 44195, OH, USA.
  • Harris TB; Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, 20251, Germany.
  • Holm H; DZHK (German Center for Cardiovascular Research) Partner Site, Hamburg/Kiel/Lübeck, Germany.
  • Ilaria G; DZHK (German Center for Cardiovascular Research) Partner Site, Hamburg/Kiel/Lübeck, Germany.
Nat Commun ; 9(1): 2904, 2018 07 25.
Article en En | MEDLINE | ID: mdl-30046033
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Nodo Atrioventricular / Función Atrial / Estudio de Asociación del Genoma Completo / Fenómenos Electrofisiológicos Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Nodo Atrioventricular / Función Atrial / Estudio de Asociación del Genoma Completo / Fenómenos Electrofisiológicos Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos