Please use this identifier to cite or link to this item: http://ktisis.cut.ac.cy/handle/10488/4399
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. 
Kontula, Kimmo K. 
Marjamaa, Annukka 
Oikarinen, Lasse 
Perola, Markus 
Porthan, Kimmo 
Erbel, Raimund M. 
Hoffmann, Per 
Jockel, Karl Heinz 
Kalsch, Hagen I M 
Nothen, Markus M. 
Lundby, Alicia 
Den Hoed, Marcel 
Loos, Ruth JF F 
Thelle, Dag Steinar 
Gieger, Christian 
Meitinger, Thomas A. 
Perz, Siegfried 
Peters, Annette 
Prucha, Hanna 
Sinner, Moritz F. 
Waldenberger, Melanie 
Gudbjartsson, Daniel Fannar 
De Boer, Rudolf A. 
Franke, Lude 
Van Der Vleuten, Pieter A. 
Beckmann, Britt Maria 
Martens, Eimo 
Bardai, Abdennasser 
Hofman, Nynke 
Wilde, Arthur Arnold Maria 
Behr, Elijah Raphael 
Dalageorgou, Chrysoula 
Noseworthy, Peter A. 
Giudicessi, John R. 
Medeiros-Domingo, Argelia 
Barc, Julien 
Kyndt, Florence 
Probst, Vincent 
Ghidoni, Alice 
Insolia, Roberto 
Hamilton, Robert Murray 
Scherer, Stephen Wayne 
Brandimarto, Jeffrey 
Eijgelsheim, Mark 
Margulies, Kenneth B. 
Moravec, Christine E. 
Del Greco M., Fabiola 
Fuchsberger, Christian 
O'Connell, Jeffrey 
Lee, Wai K. 
Watt, Graham Cm M 
Campbell, Harry 
Wild, Sarah H. 
El Mokhtari, Nour Eddine 
Bradford, Yuki 
Frey, Norbert 
Asselbergs, Folkert W. 
Leach, Irene Mateo 
Navis, Gerjan J. 
Van Den Berg, Maarten P. 
Van Veldhuisen, Dirk Jan 
Kellis, Manolis 
Krijthe, Bouwe P. 
Franco, Oscar H. 
Hofman, Albert 
Tarasov, Kirill V. 
Kors, Jan A. 
Uitterlinden, André Gerardus 
Witteman, Jacqueline C M 
Kedenko, Lyudmyla 
Lamina, Claudia 
Oostra, Ben A. 
Abecasis, Goncalo R. 
Lakatta, Edward G. 
Mulas, Antonella 
Orru, Marco 
Dorr, Marcus 
Schlessinger, David 
Uda, Manuela 
Markus, Marcello Ricardo Paulista 
Volker, Uwe U. 
Snieder, Harold 
Spector, Tim David 
Arnlov, Johan 
Lind, Lars 
Sundstrom, Johan 
Syvanen, Ann Christine 
Muller-Nurasyid, Martina 
Kivimaki, Mika 
Kahonen, Mika 
Mononen, Nina 
Raitakari, Olli T. 
Viikari, Jorma Sa A 
Adamkova, Vera 
Kiechl, Stefan G. 
Brion, Maria Jose 
Nicolaides, Andrew N. 
Paulweber, Bernhard 
Lahtinen, Annukka M. 
Haerting, Johannes 
Dominiczak, Anna F. 
Nyberg, Fredrik 
Whincup, Peter H. 
Hingorani, Aroon D. 
Schott, Jean Jacques 
Bezzina, Connie R. 
Ingelsson, Erik 
Ferrucci, Luigi 
Gasparini, Paolo 
Nolte, Ilja Maria 
Wilson, James F. 
Rudan, Igor 
Franke, Andre 
Muhleisen, Thomas Walter Alter 
Pramstaller, Peter P. 
Lehtimaki, Terho J. 
Paterson, Andrew D. 
Parsa, Afshin 
Liu, Yongmei 
Van Duijn, Cornelia M. 
Smith, Albert Vernon Ernon 
Siscovick, David S. 
Gudnason, Vilmundur G. 
Jamshidi, Yalda 
Salomaa, Veikko V. 
Felix, Stephan Burkhart Urkhart 
Sanna, Serena 
Ritchie, Marylyn D. 
Stricker, Bruno Ch Ch H 
Stefansson, Kari 
Boyer, Laurie A. 
Bis, Joshua C M 
Cappola, Thomas P. 
Olsen, Jesper Velgaard 
Lage, Kasper 
Schwartz, Peter John 
Kaab, Stefan 
Chakravarti, Aravinda H. 
Ackerman, Michael John 
Pfeufer, Arne 
De Bakker, Paul IW W 
Newton-Cheh, Christopher 
Isaacs, Aaron J. 
Newhouse, Stephen J. 
Evans, Daniel S. 
Post, Wendy S. 
Waggott, Daryl R. 
Lyytikainen, Leo Pekka 
Hicks, Andrew Antony 
Eisele, Lewin 
Ellinghaus, David 
Hayward, Caroline 
Navarro, Pau 
Ulivi, Sheila 
Tanaka, Toshiko 
Tester, David J. 
Chatel, Stephanie 
Gustafsson, Stefan E. 
Kumari, Meena 
Morris, Richard W. 
Naluai, Asa Torinsson 
Padmanabhan, Sandosh 
Kluttig, Alexander 
Strohmer, Bernhard 
Panayiotou, Andrie 
Torres, Maria Cruz 
Knoflach, Michael 
Hubacek, Jaroslav Alois 
Slowikowski, Kamil 
Raychaudhuri, Soumya 
Kumar, Runjun D. 
Harris, Tamara B. 
Launer, Lenore J. 
Shuldiner, Alan R. 
Alonso, Alvaro Alonso 
Bader, Joel S. 
Ehret, Georg B. 
Huang, Hailiang 
Kao, Wenhong 
Strait, James B. 
MacFarlane, Peter W. 
Brown, Morris J. 
Caulfield, Mark J. 
Samani, Nilesh J. 
Kronenberg, Florian 
Willeit, Johann 
Smith, Jarrett Gustav 
Greiser, Karin Halina 
Zu Schwabedissen, Henriette Meyer 
Werdan, Karl 
Carella, Massimo 
Zelante, Leopoldo L. 
Heckbert, Susan R. 
Psaty, Bruce M. 
Rotter, Jerome I. 
Kolcic, Ivana 
Polasek, Ozren 
Wright, Alan F. 
Griffin, Maura B. 
Daly, Mark J. 
Arnar, David O 
Holm, Hilma A. 
Thorsteinsdottir, Unnur 
Denny, Joshua C. 
Roden, Dan M. 
Zuvich, Rebecca Lynn 
Emilsson, Valur 
Plump, Andrew S. 
Larson, Martin G. 
O'Donnell, Christopher J. 
Yin, Xiaoyan 
Bobbo, Marco 
d'Adamo, Adamo Pio 
Iorio, Annamaria M. 
Sinagra, Gianfranco F. 
Carracedo, Angel M. 
Cummings, Steven Ron 
Nalls, Michael A. 
Jula, Antti M. 
Keywords: Calcium signaling;Cardiovascular risk;Controlled study;Gene expression;Genetic association;Genetic variability;Heart electrophysiology;Heart ventricle arrhythmia
Category: Clinical Medicine
Field: Medical and Health Sciences
Issue Date: Aug-2014
Publisher: Nature Publishing Group
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: http://ktisis.cut.ac.cy/handle/10488/4399
http://hdl.handle.net/10488/4399
ISSN: 1546-1718
DOI: 10.1038/ng.3014
Rights: © Nature America, Inc.
Type: Article
Appears in Collections:Άρθρα/Articles

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