Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
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Authors
Arking, Dan EPulit, Sara L
Crotti, Lia
van der Harst, Pim
Munroe, Patricia B
Koopmann, Tamara T
Sotoodehnia, Nona
Rossin, Elizabeth J
Morley, Michael
Wang, Xinchen
Johnson, Andrew D
Pfeufer, Arne
de Bakker, Paul I W
Bobbo, Marco
Viikari, Jorma S
Larson, Martin G
Newton-Cheh, Christopher
Hayward, Caroline
Isaacs, Aaron
Brion, Maria
Dörr, Marcus
Frey, Norbert
Scherer, Stephen W
Mulas, Antonella
Kälsch, Hagen
Newhouse, Stephen J
Evans, Daniel S
Kiechl, Stefan
Post, Wendy S
Wright, Alan F
Waggott, Daryl
Kähönen, Mika
Asselbergs, Folkert W
Stricker, Bruno H
Navarro, Pau
Ulivi, Sheila
Tanaka, Toshiko
Wilde, Arthur A M
Tester, David J
O'Donnell, Christopher J
Sinner, Moritz F
Chatel, Stéphanie
Panayiotou, Andrie G
Lage, Kasper
Hofman, Albert
Bezzina, Connie R
Noseworthy, Peter A
Torres, Maria
Knoflach, Michael
Hubacek, Jaroslav A
Margulies, Kenneth
Slowikowski, Kamil
Jöckel, Karl-Heinz
Giudicessi, John R
Perola, Markus
Behr, Elijah R
Raychaudhuri, Soumya
Mononen, Nina
Macfarlane, Peter W
Bis, Joshua C
Orrú, Marco
Pramstaller, Peter P
O'Connell, Jeffrey R
Brown, Morris
Caulfield, Mark J
Boyer, Laurie A
Samani, Nilesh J
Waldenberger, Melanie
Kronenberg, Florian
Sanna, Serena
Nöthen, Markus M
Werdan, Karl
Carella, Massimo
Tarasov, Kirill V
Zelante, Leopoldo
Dalageorgou, Chrysoula
Mateo Leach, Irene
Heckbert, Susan R
Lundby, Alicia
Ingelsson, Erik
Launer, Lenore J
Daly, Mark J
Arnar, David O
Hólm, Hilma
Schlessinger, David
Thorsteinsdottir, Unnur
Fuchsberger, Christian
Witteman, Jacqueline C M
Kors, Jan A
Denny, Joshua C
D'Adamo, Adamo P
Strait, James B
Lehtimäki, Terho J
Lyytikäinen, Leo-Pekka
Völker, Uwe
Iorio, Annamaria
Sinagra, Gianfranco
Carracedo, Angel
Navis, Gerjan
Adamkova, Vera
Cummings, Steven R
Nalls, Michael A
Snieder, Harold
Shuldiner, Alan R
Uda, Manuela
Jula, Antti
Gudbjartsson, Daníel F
Loos, Ruth J F
Ehret, Georg
Hoffmann, Per
Ritchie, Marylyn D
Gustafsson, Stefan
Paulweber, Bernhard
Thelle, Dag S
Gieger, Christian
Bader, Joel S
Meitinger, Thomas
Uitterlinden, André G
Perz, Siegfried
Kumar, Runjun D
Emilsson, Valur
de Boer, Rudolf A
Franke, Lude
van der Vleuten, Pieter A
Paterson, Andrew D
Beckmann, Britt Maria
Markus, Marcello R P
Ferrucci, Luigi
Martens, Eimo
Medeiros-Domingo, Argelia
Hicks, Andrew A
Willeit, Johann
Oikarinen, Lasse
Barc, Julien
Kyndt, Florence
Probst, Vincent
Stefansson, Kari
Ghidoni, Alice
Nicolaides, Andrew N
van Duijn, Cornelia M
Parsa, Afshin
Insolia, Roberto
Harris, Tamara B
Watt, Graham C M
den Hoed, Marcel
Kumari, Meena
Psaty, Bruce M
Olsen, Jesper V
Campbell, Harry
Wild, Sarah H
El Mokhtari, Nour E
Gasparini, Paolo
Bradford, Yuki
Roden, Dan M
Lahtinen, Annukka M
van den Berg, Maarten P
van Veldhuisen, Dirk J
Erbel, Raimund
Kellis, Manolis
Liu, Yongmei
Krijthe, Bouwe P
Kontula, Kimmo K
Smith, J Gustav
Brandimarto, Jeffrey
Kedenko, Lyudmyla
Lamina, Claudia
Oostra, Ben A
Morris, Richard W
Abecasis, Gonçalo R
Cappola, Thomas P
Eisele, Lewin
Lakatta, Edward G
Spector, Timothy D
Lee, Wai K
Rotter, Jerome I
Peters, Annette
Kluttig, Alexander
Arnlöv, Johan
Lind, Lars
Sundström, Johan
Alonso, Alvaro
Syvänen, Ann-Christine
Müller-Nurasyid, Martina
Strohmer, Bernhard
Eijgelsheim, Mark
Naluai, Asa T
Kivimaki, Mika
Marjamaa, Annukka
Dominiczak, Anna F
Greco M, Fabiola Del
Zuvich, Rebecca L
Bardai, Abdennasser
Kao, W H Linda
Nyberg, Fredrik
Whincup, Peter H
Moravec, Christine E
Hingorani, Aroon D
Ellinghaus, David
Schott, Jean-Jacques
Hamilton, Robert M
Nolte, Ilja M
Wilson, James F
Rudan, Igor
Kolcic, Ivana
Franke, Andre
Padmanabhan, Sandosh
Greiser, Karin H
Mühleisen, Thomas W
Smith, Albert Vernon
Prucha, Hanna
Raitakari, Olli T
Siscovick, David S
Gudnason, Vilmundur
Jamshidi, Yalda
Plump, Andrew S
Salomaa, Veikko
Huang, Hailiang
Griffin, Maura
Polašek, Ozren
Felix, Stephan B
Schwartz, Peter J
Haerting, Johannes
Hofman, Nynke
Franco, Oscar H
Yin, Xiaoyan
Kääb, Stefan
Chakravarti, Aravinda
Ackerman, Michael J
Meyer Zu Schwabedissen, Henriette
Porthan, Kimmo
Issue Date
2014-08
Metadata
Show full item recordCitation
Nat. Genet. 2014, 46 (8):826-36Abstract
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.Description
To access publisher's full text version of this article click on the hyperlink at the bottom of the pageAdditional Links
http://dx.doi.org/10.1038/ng.3014http://www.nature.com/ng/journal/v46/n8/pdf/ng.3014.pdf
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Archived with thanks to Nature geneticsae974a485f413a2113503eed53cd6c53
10.1038/ng.3014
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