Please use this identifier to cite or link to this item:
https://hdl.handle.net/20.500.14279/3665
Title: | Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization | Authors: | Arking, Dan E E. Pulit, Sara L. Crotti, Lia Van Der Harst, Pim Munroe, Patricia B. Koopmann, Tamara T. Sotoodehnia, Nona Rossin, Elizabeth J. Morley, Michael P. Wang, Xinchen Johnson, Andrew D. Roden, Dan M. Zuvich, Rebecca Lynn Emilsson, Valur Viikari, Jorma Sa A Plump, Andrew S. Larson, Martin G. Den Hoed, Marcel O'Donnell, Christopher J. Yin, Xiaoyan O'Connell, Jeffrey Sanna, Serena Bobbo, Marco d'Adamo, Adamo Pio Iorio, Annamaria M. Sinagra, Gianfranco F. Carracedo, Angel M. Adamkova, Vera Cummings, Steven Ron Nalls, Michael A. Jula, Antti M. Loos, Ruth JF F Ritchie, Marylyn D. Paulweber, Bernhard Thelle, Dag Steinar Gieger, Christian Meitinger, Thomas A. Perz, Siegfried Peters, Annette Prucha, Hanna Kiechl, Stefan G. Sinner, Moritz F. Waldenberger, Melanie Stricker, Bruno Ch Ch H Gudbjartsson, Daniel Fannar Kumar, Runjun D. De Boer, Rudolf A. Franke, Lude Van Der Vleuten, Pieter A. Beckmann, Britt Maria Martens, Eimo Bardai, Abdennasser Hofman, Nynke Brion, Maria Jose Perola, Markus Wilde, Arthur Arnold Maria Behr, Elijah Raphael Lee, Wai K. Dalageorgou, Chrysoula Noseworthy, Peter A. Giudicessi, John R. Medeiros-Domingo, Argelia Barc, Julien Kyndt, Florence Probst, Vincent Stefansson, Kari Ghidoni, Alice Nicolaides, Andrew N. Insolia, Roberto Watt, Graham Cm M Campbell, Harry Wild, Sarah H. El Mokhtari, Nour Eddine Bradford, Yuki Frey, Norbert Asselbergs, Folkert W. Boyer, Laurie A. Leach, Irene Mateo Navis, Gerjan J. Harris, Tamara B. Lahtinen, Annukka M. Van Den Berg, Maarten P. Van Veldhuisen, Dirk Jan Kellis, Manolis Krijthe, Bouwe P. Franco, Oscar H. Hofman, Albert Bis, Joshua C M Tarasov, Kirill V. Kors, Jan A. Uitterlinden, André Gerardus Launer, Lenore J. Witteman, Jacqueline C M Kontula, Kimmo K. Kedenko, Lyudmyla Lamina, Claudia Oostra, Ben A. Abecasis, Goncalo R. Cappola, Thomas P. Lakatta, Edward G. Mulas, Antonella Orru, Marco Dorr, Marcus Shuldiner, Alan R. Schlessinger, David Uda, Manuela Haerting, Johannes Markus, Marcello Ricardo Paulista Volker, Uwe U. Olsen, Jesper Velgaard Snieder, Harold Spector, Tim David Arnlov, Johan Lind, Lars Sundstrom, Johan Alonso, Álvaro Syvanen, Ann Christine Muller-Nurasyid, Martina Kivimaki, Mika Dominiczak, Anna F. Kao, Wenhong Nyberg, Fredrik Whincup, Peter H. Hingorani, Aroon D. Schott, Jean Jacques Bezzina, Connie R. Ingelsson, Erik Bader, Joel S. Ferrucci, Luigi Gasparini, Paolo Marjamaa, Annukka Hamilton, Robert Murray Nolte, Ilja Maria Wilson, James F. Rudan, Igor Franke, Andre Muhleisen, Thomas Walter Alter Pramstaller, Peter P. Lehtimaki, Terho J. Ehret, Georg B. Paterson, Andrew D. Parsa, Afshin Lage, Kasper Liu, Yongmei Oikarinen, Lasse Van Duijn, Cornelia M. Smith, Albert Vernon Ernon Siscovick, David S. Gudnason, Vilmundur G. Jamshidi, Yalda Salomaa, Veikko V. Huang, Hailiang Felix, Stephan Burkhart Urkhart Schwartz, Peter John Kaab, Stefan Chakravarti, Aravinda H. Ackerman, Michael John Porthan, Kimmo Pfeufer, Arne De Bakker, Paul IW W Newton-Cheh, Christopher Isaacs, Aaron J. Scherer, Stephen Wayne Kalsch, Hagen I M Newhouse, Stephen J. Evans, Daniel S. Post, Wendy S. Waggott, Daryl R. Lyytikainen, Leo Pekka Hicks, Andrew Antony Erbel, Raimund M. Eisele, Lewin Ellinghaus, David Brandimarto, Jeffrey Hayward, Caroline Kahonen, Mika Navarro, Pau Ulivi, Sheila Tanaka, Toshiko Tester, David J. Chatel, Stephanie Gustafsson, Stefan E. Kumari, Meena Hoffmann, Per Eijgelsheim, Mark Morris, Richard W. Naluai, Asa Torinsson Strait, James B. Padmanabhan, Sandosh Kluttig, Alexander Strohmer, Bernhard Panayiotou, Andrie Torres, Maria Cruz Knoflach, Michael Hubacek, Jaroslav Alois Margulies, Kenneth B. Slowikowski, Kamil Jockel, Karl Heinz Raychaudhuri, Soumya MacFarlane, Peter W. Brown, Morris J. Caulfield, Mark J. Samani, Nilesh J. Kronenberg, Florian Willeit, Johann Smith, Jarrett Gustav Moravec, Christine E. Greiser, Karin Halina Zu Schwabedissen, Henriette Meyer Mononen, Nina Nothen, Markus M. Werdan, Karl Carella, Massimo Zelante, Leopoldo L. Heckbert, Susan R. Psaty, Bruce M. Rotter, Jerome I. Del Greco M., Fabiola Kolcic, Ivana Polasek, Ozren Wright, Alan F. Raitakari, Olli T. Griffin, Maura B. Lundby, Alicia Daly, Mark J. Arnar, David O Holm, Hilma A. Thorsteinsdottir, Unnur Fuchsberger, Christian Denny, Joshua C. |
Major Field of Science: | Medical and Health Sciences | Field Category: | Clinical Medicine | Keywords: | Calcium signaling;Cardiovascular risk;Controlled study;Gene expression;Genetic association;Genetic variability;Heart electrophysiology;Heart ventricle arrhythmia | Issue Date: | Aug-2014 | Source: | Nature Genetics, 2014, Volume 46, Issue 8, Pages 826-836 | Abstract: | The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. | URI: | https://hdl.handle.net/20.500.14279/3665 | ISSN: | 15461718 | DOI: | 10.1038/ng.3014 | Rights: | © Nature America, Inc. | Type: | Article | Affiliation : | Johns Hopkins University Massachusetts General Hospital University Medical Center Utrecht University of Pavia Istituto Auxologico Italiano Institute of Harvard and MIT University of Groningen Queen Mary University of London University of Washington Netherlands Consortium for Healthy Aging Casa Sollievo della Sofferenza University Medicine Greifswald German Center for Cardiovascular Research Ludwig Maximilians University German Research Center for Environmental Health University of Groningen Icelandic Heart Association University of Iceland Erasmus University Rotterdam California Pacific Medical Center Research Institute Ontario Institute for Cancer Research Institute for Maternal and Child Health University of Tampere Center for Biomedicine University Duisburg-Essen University of Kiel Western General Hospital Mayo Clinic Université de Nantes Karolinska Institutet Uppsala University University College London University of Gothenburg Biobanking and Molecular Resource Infrastructure of Sweden University of Glasgow Martin Luther University Halle-Wittenberg Institute for Clinical and Experimental Medicine Paracelsus Medical University Cyprus University of Technology Cyprus Cardiovascular Disease and Educational Research Trust Universidade de Santiago de Compostela Innsbruck Medical University Partners HealthCare Center for Personalized Genetic Medicine Brigham and Women's Hospital The University of Manchester Washington University University of Maryland Veterans Administration Medical Center University of Minnesota University of Cambridge Group Health Cooperative University of Leicester Innsbruck Medical University Lund University German Cancer Research Center University of Greifswald University Halle-Wittenberg Harbor-University of California University of Split Vascular Screening and Diagnostic Center Landspítali University Hospital Sanofi Research and Development Boston University University of Trieste Servicio Galego de Saude Addenbrooke's Hospital King Abdulaziz University US National Institutes of Health National Institute for Health and Welfare University of Helsinki University of Tartu University of Bonn University of Basel Mindich Child Health and Development Institute University of Oslo Technische Universität München Christine Kühne-Center for Allergy and Education Hospital of Friedberg Academic Medical Centre Centre of Excellence in Research of Hereditary Disorders St George's University of London Hospital for Sick Children Research Institute CNR - National Research Council of Italy University of Michigan University of Glasgow The University of Edinburgh University of Kiel Interuniversity Cardiology Institute of the Netherlands University Medical Center Utrecht University Medical Center Groningen Ernst Moritz Arndt University Greifswald King's College London Dalarna University Turku University Hospital University of Turku AstraZeneca Research and Development University of Oxford Research Centre Juelich Harvard University University of Lübeck General Central Hospital Hospital for Sick Children Research Institute Wake Forest University Pennsylvania State University Inspectorate of Health Care Technical University of Denmark Helmholtz Zentrum München University Medical Center Utrecht University of Pennsylvania Massachusetts Institute of Technology National Heart,Lung,and Blood Institute (NHLBI) University of Copenhagen Erasmus University Rotterdam Vanderbilt University National Institute on Aging |
Publication Type: | Peer Reviewed |
Appears in Collections: | Άρθρα/Articles |
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