Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 2819155
Author(s) Arking, DE; Pulit, SL; Crotti, L; van der Harst, P; Munroe, PB; Koopmann, TT; Sotoodehnia, N; Rossin, EJ; Morley, M; Wang, X; Johnson, AD; Lundby, A; Gudbjartsson, DF; Noseworthy, PA; Eijgelsheim, M; Bradford, Y; Tarasov, KV; Dörr, M; Müller-Nurasyid, M; Lahtinen, AM; Nolte, IM; Smith, AV; Bis, JC; Isaacs, A; Newhouse, SJ; Evans, DS; Post, WS; Waggott, D; Lyytikäinen, LP; Hicks, AA; Eisele, L; Ellinghaus, D; Hayward, C; Navarro, P; Ulivi, S; Tanaka, T; Tester, DJ; Chatel, S; Gustafsson, S; Kumari, M; Morris, RW; Naluai, ÅT; Padmanabhan, S; Kluttig, A; Strohmer, B; Panayiotou, AG; Torres, M; Knoflach, M; Hubacek, JA; Slowikowski, K; Raychaudhuri, S; Kumar, RD; Harris, TB; Launer, LJ; Shuldiner, AR; Alonso, A; Bader, JS; Ehret, G; Huang, H; Kao, WH; Strait, JB; Macfarlane, PW; Brown, M; Caulfield, MJ; Samani, NJ; Kronenberg, F; Willeit, J; CARe Consortium; COGENT Consortium; Smith, JG; Greiser, KH; Meyer zu Schwabedissen, H; Werdan, K; Carella, M; Zelante, L; Heckbert, SR; Psaty, BM; Rotter, JI; Kolcic, I; Polašek, O; Wright, AF; Griffin, M; Daly, MJ; DCCT/EDIC; Arnar, DO; Hólm, H; Thorsteinsdottir, U; eMERGE Consortium; Denny, JC; Roden, DM; Zuvich, RL; Emilsson, V; Plump, AS; Larson, MG; O'Donnell, CJ; Yin, X; Bobbo, M; D'Adamo, AP; Iorio, A; Sinagra, G; Carracedo, A; Cummings, SR; Nalls, MA; Jula, A; Kontula, KK; Marjamaa, A; Oikarinen, L; Perola, M; Porthan, K; Erbel, R; Hoffmann, P; Jöckel, KH; Kälsch, H; Nöthen, MM; HRGEN Consortium; den Hoed, M; Loos, RJ; Thelle, DS; Gieger, C; Meitinger, T; Perz, S; Peters, A; Prucha, H; Sinner, MF; Waldenberger, M; de Boer, RA; Franke, L; van der Vleuten, PA; Beckmann, BM; Martens, E; Bardai, A; Hofman, N; Wilde, AA; Behr, ER; Dalageorgou, C; Giudicessi, JR; Medeiros-Domingo, A; Barc, J; Kyndt, F; Probst, V; Ghidoni, A; Insolia, R; Hamilton, RM; Scherer, SW; Brandimarto, J; Margulies, K; Moravec, CE; del Greco, MF; Fuchsberger, C; O'Connell, JR; Lee, WK; Watt, GC; Campbell, H; Wild, SH; El Mokhtari, NE; Frey, N; Asselbergs, FW; Mateo Leach, I; Navis, G; van den Berg, MP; van Veldhuisen, DJ; Kellis, M; Krijthe, BP; Franco, OH; Hofman, A; Kors, JA; Uitterlinden, AG; Witteman, JC; Kedenko, L; Lamina, C; Oostra, BA; Abecasis, GR; Lakatta, EG; Mulas, A; Orrú, M; Schlessinger, D; Uda, M; Markus, MR; Völker, U; Snieder, H; Spector, TD; Ärnlöv, J; Lind, L; Sundström, J; Syvänen, AC; Kivimaki, M; Kähönen, M; Mononen, N; Raitakari, OT; Viikari, JS; Adamkova, V; Kiechl, S; Brion, M; Nicolaides, AN; Paulweber, B; Haerting, J; Dominiczak, AF; Nyberg, F; Whincup, PH; Hingorani, AD; Schott, JJ; Bezzina, CR; Ingelsson, E; Ferrucci, L; Gasparini, P; Wilson, JF; Rudan, I; Franke, A; Mühleisen, TW; Pramstaller, PP; Lehtimäki, TJ; Paterson, AD; Parsa, A; Liu, Y; van Duijn, CM; Siscovick, DS; Gudnason, V; Jamshidi, Y; Salomaa, V; Felix, SB; Sanna, S; Ritchie, MD; Stricker, BH; Stefansson, K; Boyer, LA; Cappola, TP; Olsen, JV; Lage, K; Schwartz, PJ; Kääb, S; Chakravarti, A; Ackerman, MJ; Pfeufer, A; de Bakker, PI; Newton, C;
Author(s) at UniBasel Meyer zu Schwabedissen, Henriette
Year 2014
Title Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
Journal Nature genetics
Volume 46(8)
Pages / Article-Number 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 similar to 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.

Publisher Nature Publ.
ISSN/ISBN 1061-4036
edoc-URL http://edoc.unibas.ch/dok/A6337653
Full Text on edoc No
Digital Object Identifier DOI 10.1038/ng.3014
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/24952745
ISI-Number WOS:000339704400010
Document type (ISI) Article
 
   

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