Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
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DOI:
10.1038/ng.3014
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发表时间:
2014-08
期刊:
影响因子:
30.8
通讯作者:
Newton-Cheh, Christopher
中科院分区:
文献类型:
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作者:
Arking, Dan E.;Pulit, 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.;Lundby, Alicia;Gudbjartsson, Daniel F.;Noseworthy, Peter A.;Eijgelsheim, Mark;Bradford, Yuki;Tarasov, Kirill V.;Dorr, Marcus;Miiller-Nurasyid, Martina;Lahtinen, Annukka M.;Nolte, Ilja M.;Smith, Albert Vernon;Bis, Joshua C.;Isaacs, Aaron;Newhouse, Stephen J.;Evans, Daniel S.;Post, Wendy S.;Waggott, Daryl;Lyytikainen, Leo-Pekka;Hicks, Andrew A.;Eisele, Lewin;Ellinghaus, David;Hayward, Caroline;Navarro, Pau;Ulivi, Sheila;Tanaka, Toshiko;Tester, David J.;Chatel, Stephanie;Gustafsson, Stefan;Kumari, Meena;Morris, Richard W.;Naluai, Asa T.;Padmanabhan, Sandosh;Kluttig, Alexander;Strohmer, Bernhard;Panayiotou, Andrie G.;Torres, Maria;Knoflach, Michael;Hubacek, Jaroslav A.;Slowikowski, Kamil;Raychaudhuri, Soumya;Kumar, Runjun D.;Harris, Tamara B.;Launer, Lenore J.;Shuldiner, Alan R.;Alonso, Alvaro;Bader, Joel S.;EhreT, Georg;Huang, Hailiang;Kao, W. H. Linda;Strait, James B.;Macfarlane, Peter W.;Brown, Morris;Caulfield, Mark J.;Samani, Nilesh J.;Kronenberg, Florian;Willeit, Johann;Smith, J. Gustav;Greiser, Karin H.;Schwabedissen, Henriette Meyer Zu;Werdan, Karl;Carella, Massimo;Zelante, Leopoldo;Heckbert, Susan R.;Psaty, Bruce M.;Rotter, Jerome I.;Kolcic, Ivana;Poagek, Ozren;Wright, Alan F.;Griffin, Maura;Daly, Mark J.;Arnar, David O.;Holm, Hilma;Thorsteinsdottir, Unnur;Denny, Joshua C.;Roden, Dan M.;Zuvich, Rebecca L.;Emilsson, Valur;Plump, Andrew S.;Larson, Martin G.;O'Donnell, Christopher J.;Yin, Xiaoyan;Bobboll, Marco;D'Adamo, Adamo P.;Iorio, Annamaria;Sinagra, Gianfranco;Carracedo, Angel;Cummings, Steven R.;Nalls, Michael A.;Jula, Antti;Kontula, Kimmo K.;Marjamaa, Annukka;Oikarinen, Lasse;Perola, Markus;Porthan, Kimmo;Erbe, Raimund;Hoffmann, Per;Jockel, Karl-Heinz;Kalsch, Hagen;Nothen, Markus M.;Den Hoed, Marcel;Loos, Ruth J. F.;Thelle, Dag S.;Gieger, Christian;Meitinger, Thomas;Perz, Siegfried;Peters, Annette;Pruchal, Hanna;Sinner, Moritz F.;Waldenberger, Melanie;De Boer, Rudolf A.;Franke, Lude;Van der Vleuten, Pieter A.;Beckmann, Britt Maria;Martens, Eimo;Bardail, Abdennasser;Hofman, Nynke;Wilde, Arthur A. M.;Behr, Elijah R.;Dalageorgou, Chrysoula;Giudicessi, John R.;Medeiros-Domingo, Argelia;Barc, Julien;Kyndt, Florence;Probst, Vincent;Ghidoni, Alice;Insolia, Roberto;Hamilton, Robert M.;Scherer, Stephen W.;Brandimarto, Jeffrey;Margulies, Kenneth;Moravec, Christine E.;Del Greco, Fabiola;Fuchsberger, Christian;O'Connell, Jeffrey R.;Lee, Wai K.;Watt, Graham C. M.;Campbell, Harry;Wild, Sarah H.;El Mokhtari, Nour E.;Frey, Norbert;Asselbergs, Folkert W.;Leach, Irene Mateo;Navis, Gerjan;Van den Berg, Maarten P.;Van Veldhuisen, Dirk J.;Kellis, Manolis;Krijthe, Bouwe P.;Franco, Oscar H.;Hofman, Albert;Kors, Jan A.;Uitterlinden, Andre G.;Witteman, Jacqueline C. M.;Kedenko, Lyudmyla;Lamina, Claudia;Oostra, Ben A.;Abecasis, Goncalo R.;Lakatta, Edward G.;Mulas, Antonella;Orru, Marco;Schlessinger, David;Uda, Manuela;Markus, Marcello R. P.;Volker, Uwe;Snieder, Harold;Spector, Timothy D.;Arnlov, Johan;Lind, Lars;Sundstrom, Johan;Syvanen, Ann-Christine;Kivimaki, Mika;Kahonen, Mika;Mononen, Nina;Raitakari, I. T.;Viikari, Jorma S.;Adamkova, Vera;Kiech, Stefan;Brion, Maria;Nicolaides, Andrew N.;Paulweber, Bernhard;Haerting, Johannes;Dominiczak, Anna F.;Nyberg, Fredrik;Whincup, Peter H.;Hingorani, Aroon D.;Schott, Jean-Jacques;Bezzina, Connie R.;Ingelsson, Erik;Ferrucci, Luigi;Gaspariniin, Paolo;Wilson, James F.;Rudan, Igor;Franke, Andre;Miihleisen, Thomas W.;Pramstaller, Peter P.;Lehtimaki, Terho J.;Paterson, Andrew D.;Parsa, Afshin;Liu, Yongmei;Van Duijn, Cornelia M.;Siscovick, David S.;Gudnason, Vilmundur;Jamshidi, Yalda;Salomaa, Veikko;Felix, Stephan B.;Sanna, Serena;Ritchie, Marylyn D.;Stricker, Bruno H.;Stefansson, Karl;Boyer, Laurie A.;Cappola, Thomas P.;Olsen, Jesper V.;Lage, Kasper;Schwartz, Peter J.;Kaab, Stefan;Chakravarti, Aravinda;Ackerman, Michael J.;Pfeufer, Arne;De Bakker, Paul I. W.;Newton-Cheh, Christopher
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 QT interval loci, that collectively explain ∼8-10% of QT variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 novel QT loci in 298 unrelated LQTS probands identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode for 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 novel candidate genes for ventricular arrhythmias, LQTS,and SCD.
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影响因子:
64.8
作者:
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者:
Bernstein, Bradley E.
影响因子:
48
作者:
Lundby, Alicia;Rossin, Elizabeth J.;Steffensen, Annette B.;Acha, Moshe Ray;Newton-Cheh, Christopher;Pfeufer, Arne;Lyneh, Stacey N.;Olesen, Soren-Peter;Brunak, Soren;Ellinor, Patrick T.;Jukema, J. Wouter;Trompet, Stella;Ford, Ian;Macfarlane, Peter W.;Krijthe, Bouwe P.;Hofman, Albert;Uitterlinden, Andre G.;Stricker, Bruno H.;Nathoe, Hendrik M.;Spiering, Wilko;Daly, Mark J.;Asselbergs, Ikea W.;van der Harst, Pim;Milan, David J.;de Bakker, Paul I. W.;Lage, Kasper;Olsen, Jesper V.
通讯作者:
Olsen, Jesper V.
影响因子:
30.8
作者:
通讯作者:
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影响因子:
30.8
作者:
Arking, Dan E.;Pfeufer, Arne;Chakravarti, Aravinda
通讯作者:
Chakravarti, Aravinda
影响因子:
30.8
作者:
通讯作者:
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