Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

zu Schwabedissen, Henriette Meyer; Ärnl, Johan; van der Harst, Pim; van der Vleuten, Pieter A.; Ärnlöv, Johan; Arking, Dan E.; del Greco, M. F.; Pulit, Sara L.; Munroe, Patricia B.; Koopmann, Tamara Tt; Van Der Harst, P.; Rossin, Elizabeth J.; De, Arking; Ad, Johnson; Johnson, Andrew D.; Gudbjartsson, Daniel F.; Noseworthy, Peter A.; Tarasov, Kirill V.; Dörr, M.; Sl, Pulit; Müller-Nurasyid, Martina; Lahtinen, Annukka M.; Im, Nolte; Av, Smith; Crotti, Lia; Nolte, Ilja M.; Jc, Bis; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Sj, Newhouse; Newhouse, Stephen J.; Ds, Evans; Evans, Daniel S.; Ws, Post; Post, Wendy S.; Waggott, Daryl; Lyytikäinen, Leo-Pekka; Lp, Lyytikäinen; Hicks, Andrew Aa; Aa, Hicks; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Naluai, Åsa T.; Tester, David J.; Dj, Tester; Chatel, Stéphanie; Gustafsson, Stefan; Kumari, Meena; Kluttig, Alexander; Rw, Morris; Panayiotou, Andrie G.; At, Naluai; Morris, Richard W.; Strohmer, Bernhard; Naluai, Asa T.; Torres, Maria; Pb, Munroe; Padmanabhan, Sandosh; Miiller-Nurasyid, Martina; Ag, Panayiotou; Sotoodehnia, Nona; Hubacek, Jaroslav A.; Knoflach, Michael; Slowikowski, Kamil; Ja, Hubacek; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Rd, Kumar; Shuldiner, Alan R.; Tb, Harris; Lj, Launer; Ar, Shuldiner; Alonso, Alvaro; Tt, Koopmann; Bader, Joel S.; Js, Bader; Ehret, Georg; Kao, Whl H. Linda; Huang, Hailiang; Strait, James B.; Morley, Michael; Wh, Kao; de Boer, Rudolf A.; Jb, Strait; Macfarlane, Peter W.; Pw, Macfarlane; Brown, Morris; Zu Schwabedissen, Hm M.; Caulfield, Mark J.; Mj, Caulfield; Samani, Nilesh J.; Nj, Samani; Wang, Xinchen; Kronenberg, Florian; Willeit, Johann; Naluai, Åt; Smith, Jg Gustav; Meyer Zu Schwabedissen, Henriette; Cogent, Consortium; Greiser, Karin H.; Jg, Smith; Schwabedissen, Henriette Meyer Zu; Kh, Greiser; Ej, Rossin; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Sr, Heckbert; Bm, Psaty; Kolcic, Ivana; Ji, Rotter; Lundby, Alicia; Wright, Alan F.; Polasek, Ozren; Poagek, Ozren; van den Berg, Maarten P.; Af, Wright; Griffin, Maura; van Veldhuisen, Dirk J.; Daly, Mark J.; Mj, Daly; Arnar, David O.; den Hoed, Marcel; Do, Arnar; Hólm, Hilma; Denny, Joshua C.; Thorsteinsdottir, Unnur; Roden, Dan M.; Zuvich, Rebecca L.; Consortium, eMERGE; Jc, Denny; Plump, Andrew S.; Larson, Martin G.; Dm, Roden; Emilsson, Valur; O'Donnell, Christopher J.; Rl, Zuvich; As, Plump; Yin, Xiaoyan; D'Adamo, Adamo P.; Eijgelsheim, Mark; Mg, Larson; Bobboll, Marco; Cj, O'Donnell; Bobbo, Marco; Iorio, Annamaria; Ap, D'Adamo; Cummings, Steven R.; Sinagra, Gianfranco; Nalls, Michael A.; Carracedo, Angel; Bradford, Yuki; Holm, Hilma; Kontula, Kimmo Kk; Sr, Cummings; Jula, Antti; Ma, Nalls; Marjamaa, Annukka; Kk, Kontula; Oikarinen, Lasse; Dcct/Edic,; Perola, Markus; Porthan, Kimmo; Erbe, Raimund; Erbel, Raimund; De Boer, Ra A.; Hoffmann, Per; Jöckel, Karl-Heinz; van Duijn, Cornelia M.; Kh, Jöckel; Den Hoed, M.; Kälsch, Hagen; Nöthen, Markus Mm; Dörr, Marcus; Van Der Vleuten, Pa A.; Mm, Nöthen; Jockel, Karl-Heinz; Hrgen, Consortium; Loos, Ruth J. F.; Kalsch, Hagen; Rj, Loos; Thelle, Dag S.; Df, Gudbjartsson; Ds, Thelle; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; de Bakker, Paul I. W.; Prucha, Hanna; Sinner, Moritz F.; Mf, Sinner; Waldenberger, Melanie; Pruchal, Hanna; Ra, de Boer; Franke, Lude; Beckmann, Britt Maria; Pa, Noseworthy; Pa, van der Vleuten; Bm, Beckmann; Martens, Eimo; Bardai, Abdennasser; Hofman, Nynke; Wilde, Arthur A. M.; Bardail, Abdennasser; Aa, Wilde; Consortium, CARe; Behr, Elijah R.; Er, Behr; Nothen, Markus M.; Dalageorgou, Chrysoula; Jr, Giudicessi; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Rm, Hamilton; Hamilton, Robert M.; Sw, Scherer; Berg, Van Den; Scherer, Stephen W.; Brandimarto, Jeffrey; O’donnell, Christopher J.; Margulies, Kenneth; Müller-Nurasyid, Martina; Ce, Moravec; Fd, Greco M.; Moravec, Christine E.; Fuchsberger, Christian; Jr, O'Connell; Van Veldhuisen, Dj J.; O'Connell, Jeffrey R.; Wk, Lee; Lee, Wai K.; Gc, Watt; Watt, Graham C. M.; Del Greco M., Fabiola; Campbell, Harry; Sh, Wild; Ne, El Mokhtari; Kv, Tarasov; Greco M., Fabiola del; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Fw, Asselbergs; Asselbergs, Folkert W.; Navis, Gerjan; Leach, Irene Mateo; Mp, van den Berg; Dj, van Veldhuisen; Kellis, Manolis; Bp, Krijthe; Krijthe, Bouwe P.; Oh, Franco; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Ja, Kors; Uitterlinden, Andre G.; Ag, Uitterlinden; Witteman, Jacqueline C. M.; Jc, Witteman; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Ba, Oostra; Abecasis, Gonçalo R.; Gr, Abecasis; Lakatta, Edward G.; Eg, Lakatta; Mulas, Antonella; Mateo Leach, Irene; Orru, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R. P.; Mr, Markus; Völker, Uwe; Spector, Timothy D.; Snieder, Harold; O’connell, Jeffrey R.; Td, Spector; Am, Lahtinen; Lind, Lars; Syvanen, Ann-Christine; Sundström, Johan; Raitakari, I. T.; Kivimaki, Mika; Ac, Syvänen; Kähönen, Mika; Raitakari, O. T.; Mononen, Nina; Raitakari, Olli T.; Kiech, Stefan; Arnlov, Johan; Viikari, Jorma S.; Ot, Raitakari; Js, Viikari; Adamkova, Vera; Kiechl, Stefan; Brion, Maria; Nicolaides, Andrew N.; An, Nicolaides; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Af, Dominiczak; Nyberg, Fredrik; Whincup, Peter H.; Ph, Whincup; Hingorani, Aroon D.; Ad, Hingorani; Schott, Jean-Jacques; Jj, Schott; Bezzina, Connie R.; Cr, Bezzina; Ingelsson, Erik; Kahonen, Mika; Ferrucci, Luigi; Gasparini, Paolo; Jf, Wilson; Wilson, James F.; Gaspariniin, Paolo; De Bakker, Piw I. W.; Rudan, Igor; Franke, Andre; Tw, Mühleisen; Pp, Pramstaller; Mühleisen, Thomas W.; Tj, Lehtimäki; Miihleisen, Thomas W.; Pramstaller, Peter Pp; Ad, Paterson; Lehtimäki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Cm, van Duijn; Liu, Yongmei; Van Duijn, C. M.; Ds, Siscovick; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Sb, Felix; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Md, Ritchie; Stricker, Bruno H.; Bh, Stricker; Stefansson, Kari; Boyer, Laurie A.; La, Boyer; Cappola, Thomas P.; Olsen, Jesper V.; Tp, Cappola; Kaab, Stefan; Jv, Olsen; Lage, Kasper; Schwartz, Peter J.; Pj, Schwartz; Kääb, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Edic, Dcct; Mj, Ackerman; Pfeufer, Arne; Pi, de Bakker; Newton-Cheh, Christopher; Kääb, Stefan

Dissemin
Kirill V. Tarasov
zu Schwabedissen et al., 2014

Published in

Nature Research, Nature Genetics, 8(46), p. 826-836, 2014

DOI: 10.1038/ng.3014

Tools

Export citation

Format

@article{zu Schwabedissen2014,
  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. © 2014 Nature America, Inc.},
  author = {zu Schwabedissen, Henriette Meyer and Ärnl, Johan and van der Harst, Pim and van der Vleuten, Pieter A. and Ärnlöv, Johan and Arking, Dan E. and del Greco, M. F. and Pulit, Sara L. and Munroe, Patricia B. and Koopmann, Tamara Tt and Van Der Harst, P. and Rossin, Elizabeth J. and De, Arking and Ad, Johnson and Johnson, Andrew D. and Gudbjartsson, Daniel F. and Noseworthy, Peter A. and Tarasov, Kirill V. and Dörr, M. and Sl, Pulit and Müller-Nurasyid, Martina and Lahtinen, Annukka M. and Im, Nolte and Av, Smith and Crotti, Lia and Nolte, Ilja M. and Jc, Bis and Smith, Albert Vernon and Bis, Joshua C. and Isaacs, Aaron and Sj, Newhouse and Newhouse, Stephen J. and Ds, Evans and Evans, Daniel S. and Ws, Post and Post, Wendy S. and Waggott, Daryl and Lyytikäinen, Leo-Pekka and Lp, Lyytikäinen and Hicks, Andrew Aa and Aa, Hicks and Eisele, Lewin and Ellinghaus, David and Hayward, Caroline and Navarro, Pau and Ulivi, Sheila and Tanaka, Toshiko and Naluai, Åsa T. and Tester, David J. and Dj, Tester and Chatel, Stéphanie and Gustafsson, Stefan and Kumari, Meena and Kluttig, Alexander and Rw, Morris and Panayiotou, Andrie G. and At, Naluai and Morris, Richard W. and Strohmer, Bernhard and Naluai, Asa T. and Torres, Maria and Pb, Munroe and Padmanabhan, Sandosh and Miiller-Nurasyid, Martina and Ag, Panayiotou and Sotoodehnia, Nona and Hubacek, Jaroslav A. and Knoflach, Michael and Slowikowski, Kamil and Ja, Hubacek and Raychaudhuri, Soumya and Kumar, Runjun D. and Harris, Tamara B. and Launer, Lenore J. and Rd, Kumar and Shuldiner, Alan R. and Tb, Harris and Lj, Launer and Ar, Shuldiner and Alonso, Alvaro and Tt, Koopmann and Bader, Joel S. and Js, Bader and Ehret, Georg and Kao, Whl H. Linda and Huang, Hailiang and Strait, James B. and Morley, Michael and Wh, Kao and de Boer, Rudolf A. and Jb, Strait and Macfarlane, Peter W. and Pw, Macfarlane and Brown, Morris and Zu Schwabedissen, Hm M. and Caulfield, Mark J. and Mj, Caulfield and Samani, Nilesh J. and Nj, Samani and Wang, Xinchen and Kronenberg, Florian and Willeit, Johann and Naluai, Åt and Smith, Jg Gustav and Meyer Zu Schwabedissen, Henriette and Cogent, Consortium and Greiser, Karin H. and Jg, Smith and Schwabedissen, Henriette Meyer Zu and Kh, Greiser and Ej, Rossin and Werdan, Karl and Carella, Massimo and Zelante, Leopoldo and Heckbert, Susan R. and Psaty, Bruce M. and Rotter, Jerome I. and Sr, Heckbert and Bm, Psaty and Kolcic, Ivana and Ji, Rotter and Lundby, Alicia and Wright, Alan F. and Polasek, Ozren and Poagek, Ozren and van den Berg, Maarten P. and Af, Wright and Griffin, Maura and van Veldhuisen, Dirk J. and Daly, Mark J. and Mj, Daly and Arnar, David O. and den Hoed, Marcel and Do, Arnar and Hólm, Hilma and Denny, Joshua C. and Thorsteinsdottir, Unnur and Roden, Dan M. and Zuvich, Rebecca L. and Consortium, eMERGE and Jc, Denny and Plump, Andrew S. and Larson, Martin G. and Dm, Roden and Emilsson, Valur and O'Donnell, Christopher J. and Rl, Zuvich and As, Plump and Yin, Xiaoyan and D'Adamo, Adamo P. and Eijgelsheim, Mark and Mg, Larson and Bobboll, Marco and Cj, O'Donnell and Bobbo, Marco and Iorio, Annamaria and Ap, D'Adamo and Cummings, Steven R. and Sinagra, Gianfranco and Nalls, Michael A. and Carracedo, Angel and Bradford, Yuki and Holm, Hilma and Kontula, Kimmo Kk and Sr, Cummings and Jula, Antti and Ma, Nalls and Marjamaa, Annukka and Kk, Kontula and Oikarinen, Lasse and Dcct/Edic,  and Perola, Markus and Porthan, Kimmo and Erbe, Raimund and Erbel, Raimund and De Boer, Ra A. and Hoffmann, Per and Jöckel, Karl-Heinz and van Duijn, Cornelia M. and Kh, Jöckel and Den Hoed, M. and Kälsch, Hagen and Nöthen, Markus Mm and Dörr, Marcus and Van Der Vleuten, Pa A. and Mm, Nöthen and Jockel, Karl-Heinz and Hrgen, Consortium and Loos, Ruth J. F. and Kalsch, Hagen and Rj, Loos and Thelle, Dag S. and Df, Gudbjartsson and Ds, Thelle and Gieger, Christian and Meitinger, Thomas and Perz, Siegfried and Peters, Annette and de Bakker, Paul I. W. and Prucha, Hanna and Sinner, Moritz F. and Mf, Sinner and Waldenberger, Melanie and Pruchal, Hanna and Ra, de Boer and Franke, Lude and Beckmann, Britt Maria and Pa, Noseworthy and Pa, van der Vleuten and Bm, Beckmann and Martens, Eimo and Bardai, Abdennasser and Hofman, Nynke and Wilde, Arthur A. M. and Bardail, Abdennasser and Aa, Wilde and Consortium, CARe and Behr, Elijah R. and Er, Behr and Nothen, Markus M. and Dalageorgou, Chrysoula and Jr, Giudicessi and Giudicessi, John R. and Medeiros-Domingo, Argelia and Barc, Julien and Kyndt, Florence and Probst, Vincent and Ghidoni, Alice and Insolia, Roberto and Rm, Hamilton and Hamilton, Robert M. and Sw, Scherer and Berg, Van Den and Scherer, Stephen W. and Brandimarto, Jeffrey and O’donnell, Christopher J. and Margulies, Kenneth and Müller-Nurasyid, Martina and Ce, Moravec and Fd, Greco M. and Moravec, Christine E. and Fuchsberger, Christian and Jr, O'Connell and Van Veldhuisen, Dj J. and O'Connell, Jeffrey R. and Wk, Lee and Lee, Wai K. and Gc, Watt and Watt, Graham C. M. and Del Greco M., Fabiola and Campbell, Harry and Sh, Wild and Ne, El Mokhtari and Kv, Tarasov and Greco M., Fabiola del and Wild, Sarah H. and El Mokhtari, Nour E. and Frey, Norbert and Fw, Asselbergs and Asselbergs, Folkert W. and Navis, Gerjan and Leach, Irene Mateo and Mp, van den Berg and Dj, van Veldhuisen and Kellis, Manolis and Bp, Krijthe and Krijthe, Bouwe P. and Oh, Franco and Franco, Oscar H. and Hofman, Albert and Kors, Jan A. and Ja, Kors and Uitterlinden, Andre G. and Ag, Uitterlinden and Witteman, Jacqueline C. M. and Jc, Witteman and Kedenko, Lyudmyla and Lamina, Claudia and Oostra, Ben A. and Ba, Oostra and Abecasis, Gonçalo R. and Gr, Abecasis and Lakatta, Edward G. and Eg, Lakatta and Mulas, Antonella and Mateo Leach, Irene and Orru, Marco and Schlessinger, David and Uda, Manuela and Markus, Marcello R. P. and Mr, Markus and Völker, Uwe and Spector, Timothy D. and Snieder, Harold and O’connell, Jeffrey R. and Td, Spector and Am, Lahtinen and Lind, Lars and Syvanen, Ann-Christine and Sundström, Johan and Raitakari, I. T. and Kivimaki, Mika and Ac, Syvänen and Kähönen, Mika and Raitakari, O. T. and Mononen, Nina and Raitakari, Olli T. and Kiech, Stefan and Arnlov, Johan and Viikari, Jorma S. and Ot, Raitakari and Js, Viikari and Adamkova, Vera and Kiechl, Stefan and Brion, Maria and Nicolaides, Andrew N. and An, Nicolaides and Paulweber, Bernhard and Haerting, Johannes and Dominiczak, Anna F. and Af, Dominiczak and Nyberg, Fredrik and Whincup, Peter H. and Ph, Whincup and Hingorani, Aroon D. and Ad, Hingorani and Schott, Jean-Jacques and Jj, Schott and Bezzina, Connie R. and Cr, Bezzina and Ingelsson, Erik and Kahonen, Mika and Ferrucci, Luigi and Gasparini, Paolo and Jf, Wilson and Wilson, James F. and Gaspariniin, Paolo and De Bakker, Piw I. W. and Rudan, Igor and Franke, Andre and Tw, Mühleisen and Pp, Pramstaller and Mühleisen, Thomas W. and Tj, Lehtimäki and Miihleisen, Thomas W. and Pramstaller, Peter Pp and Ad, Paterson and Lehtimäki, Terho J. and Paterson, Andrew D. and Parsa, Afshin and Cm, van Duijn and Liu, Yongmei and Van Duijn, C. M. and Ds, Siscovick and Siscovick, David S. and Gudnason, Vilmundur and Jamshidi, Yalda and Salomaa, Veikko and Sb, Felix and Felix, Stephan B. and Sanna, Serena and Ritchie, Marylyn D. and Md, Ritchie and Stricker, Bruno H. and Bh, Stricker and Stefansson, Kari and Boyer, Laurie A. and La, Boyer and Cappola, Thomas P. and Olsen, Jesper V. and Tp, Cappola and Kaab, Stefan and Jv, Olsen and Lage, Kasper and Schwartz, Peter J. and Pj, Schwartz and Kääb, Stefan and Chakravarti, Aravinda and Ackerman, Michael J. and Edic, Dcct and Mj, Ackerman and Pfeufer, Arne and Pi, de Bakker and Newton-Cheh, Christopher and Kääb, Stefan},
  doi = {10.1038/ng.3014},
  journal = {Nature Genetics},
  month = {jun},
  pages = {826-836},
  title = {Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization},
  url = {http://www.nature.com/articles/ng.3014.pdf},
  volume = {46},
  year = {2014}
}

Download

Export citation

Search in Google Scholar

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Journal article published in 2014 by Henriette Meyer zu Schwabedissen, Johan Ärnl, Pim van der Harst, Pieter A. van der Vleuten, Johan Ärnlöv, Dan E. Arking, M. F. del Greco, Sara L. Pulit, Patricia B. Munroe, Tamara Tt Koopmann, P. Van Der Harst, Elizabeth J. Rossin, Arking De, Johnson Ad, Andrew D. Johnson and other authors. Henriette Meyer zu Schwabedissen, Johan Ärnl, Pim van der Harst, Pieter A. van der Vleuten, Johan Ärnlöv, Dan E. Arking, M. F. del Greco, Sara L. Pulit, Patricia B. Munroe, Tamara Tt Koopmann, P. Van Der Harst, Elizabeth J. Rossin, Arking De, Johnson Ad, Andrew D. Johnson, Daniel F. Gudbjartsson, Peter A. Noseworthy, Kirill V. Tarasov

, M. Dörr, Pulit Sl, Martina Müller-Nurasyid, Annukka M. Lahtinen, Nolte Im, Smith Av, Lia Crotti, Ilja M. Nolte, Bis Jc, Albert Vernon Smith

, Joshua C. Bis, Aaron Isaacs, Newhouse Sj, Stephen J. Newhouse, Evans Ds, Daniel S. Evans, Post Ws, Wendy S. Post, Daryl Waggott, Leo-Pekka Lyytikäinen, Lyytikäinen Lp, Andrew Aa Hicks

, Hicks Aa, Lewin Eisele, David Ellinghaus, Caroline Hayward, Pau Navarro

, Sheila Ulivi

, Toshiko Tanaka, Åsa T. Naluai, David J. Tester, Tester Dj, Stéphanie Chatel, Stefan Gustafsson, Meena Kumari, Alexander Kluttig, Morris Rw, Andrie G. Panayiotou, Naluai At, Richard W. Morris, Bernhard Strohmer, Asa T. Naluai

, Maria Torres, Munroe Pb, Sandosh Padmanabhan, Martina Miiller-Nurasyid, Panayiotou Ag, Nona Sotoodehnia, Jaroslav A. Hubacek, Michael Knoflach, Kamil Slowikowski

, Hubacek Ja, Soumya Raychaudhuri, Runjun D. Kumar, Tamara B. Harris, Lenore J. Launer, Kumar Rd, Alan R. Shuldiner, Harris Tb, Launer Lj, Shuldiner Ar, Alvaro Alonso, Koopmann Tt, Joel S. Bader

, Bader Js, Georg Ehret, Whl H. Linda Kao, Hailiang Huang, James B. Strait, Michael Morley, Kao Wh, Rudolf A. de Boer, Strait Jb, Peter W. Macfarlane, Macfarlane Pw, Morris Brown, Hm M. Zu Schwabedissen, Mark J. Caulfield, Caulfield Mj, Nilesh J. Samani, Samani Nj, Xinchen Wang

, Florian Kronenberg, Johann Willeit, Åt Naluai, Jg Gustav Smith, Henriette Meyer Zu Schwabedissen, Consortium Cogent, Karin H. Greiser, Smith Jg, Henriette Meyer Zu Schwabedissen, Greiser Kh, Rossin Ej, Karl Werdan, Massimo Carella, Leopoldo Zelante, Susan R. Heckbert, Bruce M. Psaty, Jerome I. Rotter, Heckbert Sr, Psaty Bm, Ivana Kolcic, Rotter Ji, Alicia Lundby

, Alan F. Wright, Ozren Polasek, Ozren Poagek, Maarten P. van den Berg, Wright Af, Maura Griffin, Dirk J. van Veldhuisen, Mark J. Daly, Daly Mj, David O. Arnar, Marcel den Hoed

, Arnar Do, Hilma Hólm, Joshua C. Denny, Unnur Thorsteinsdottir, Dan M. Roden, Rebecca L. Zuvich, eMERGE Consortium, Denny Jc, Andrew S. Plump, Martin G. Larson, Roden Dm, Valur Emilsson, Christopher J. O'Donnell, Zuvich Rl, Plump As, Xiaoyan Yin, Adamo P. D'Adamo

, Mark Eijgelsheim, Larson Mg, Marco Bobboll, O'Donnell Cj, Marco Bobbo, Annamaria Iorio, D'Adamo Ap, Steven R. Cummings, Gianfranco Sinagra

, Michael A. Nalls, Angel Carracedo, Yuki Bradford, Hilma Holm, Kimmo Kk Kontula, Cummings Sr, Antti Jula, Nalls Ma, Annukka Marjamaa, Kontula Kk, Lasse Oikarinen, Dcct/Edic, Markus Perola, Kimmo Porthan, Raimund Erbe, Raimund Erbel, Ra A. De Boer, Per Hoffmann, Karl-Heinz Jöckel, Cornelia M. van Duijn, Jöckel Kh, M. Den Hoed, Hagen Kälsch, Markus Mm Nöthen, Marcus Dörr, Pa A. Van Der Vleuten, Nöthen Mm, Karl-Heinz Jockel, Consortium Hrgen, Ruth J. F. Loos, Hagen Kalsch, Loos Rj, Dag S. Thelle, Gudbjartsson Df, Thelle Ds, Christian Gieger

, Thomas Meitinger, Siegfried Perz, Annette Peters, Paul I. W. de Bakker, Hanna Prucha, Moritz F. Sinner, Sinner Mf, Melanie Waldenberger, Hanna Pruchal, de Boer Ra, Lude Franke

, Britt Maria Beckmann, Noseworthy Pa, van der Vleuten Pa, Beckmann Bm, Eimo Martens, Abdennasser Bardai, Nynke Hofman, Arthur A. M. Wilde, Abdennasser Bardail, Wilde Aa, CARe Consortium, Elijah R. Behr, Behr Er, Markus M. Nothen, Chrysoula Dalageorgou, Giudicessi Jr, John R. Giudicessi

, Argelia Medeiros-Domingo, Julien Barc, Florence Kyndt, Vincent Probst, Alice Ghidoni, Roberto Insolia, Hamilton Rm, Robert M. Hamilton, Scherer Sw, Van Den Berg, Stephen W. Scherer, Jeffrey Brandimarto, Christopher J. O’donnell, Kenneth Margulies, Martina Müller-Nurasyid, Moravec Ce, Greco M. Fd, Christine E. Moravec, Christian Fuchsberger, O'Connell Jr, Dj J. Van Veldhuisen, Jeffrey R. O'Connell, Lee Wk, Wai K. Lee, Watt Gc, Graham C. M. Watt, Fabiola Del Greco M., Harry Campbell, Wild Sh, El Mokhtari Ne, Tarasov Kv, Fabiola del Greco M., Sarah H. Wild, Nour E. El Mokhtari, Norbert Frey, Asselbergs Fw, Folkert W. Asselbergs, Gerjan Navis, Irene Mateo Leach, van den Berg Mp, van Veldhuisen Dj, Manolis Kellis, Krijthe Bp, Bouwe P. Krijthe, Franco Oh, Oscar H. Franco, Albert Hofman, Jan A. Kors, Kors Ja, Andre G. Uitterlinden, Uitterlinden Ag, Jacqueline C. M. Witteman, Witteman Jc, Lyudmyla Kedenko, Claudia Lamina, Ben A. Oostra, Oostra Ba, Gonçalo R. Abecasis, Abecasis Gr, Edward G. Lakatta, Lakatta Eg, Antonella Mulas, Irene Mateo Leach, Marco Orru, David Schlessinger, Manuela Uda, Marcello R. P. Markus, Markus Mr, Uwe Völker, Timothy D. Spector, Harold Snieder, Jeffrey R. O’connell, Spector Td, Lahtinen Am, Lars Lind, Ann-Christine Syvanen, Johan Sundström, I. T. Raitakari, Mika Kivimaki

, Syvänen Ac, Mika Kähönen, O. T. Raitakari, Nina Mononen, Olli T. Raitakari, Stefan Kiech, Johan Arnlov, Jorma S. Viikari, Raitakari Ot, Viikari Js, Vera Adamkova, Stefan Kiechl, Maria Brion, Andrew N. Nicolaides, Nicolaides An, Bernhard Paulweber, Johannes Haerting, Anna F. Dominiczak, Dominiczak Af, Fredrik Nyberg, Peter H. Whincup, Whincup Ph, Aroon D. Hingorani, Hingorani Ad, Jean-Jacques Schott, Schott Jj, Connie R. Bezzina, Bezzina Cr, Erik Ingelsson, Mika Kahonen, Luigi Ferrucci, Paolo Gasparini, Wilson Jf, James F. Wilson, Paolo Gaspariniin, Piw I. W. De Bakker, Igor Rudan

, Andre Franke, Mühleisen Tw, Pramstaller Pp, Thomas W. Mühleisen, Lehtimäki Tj, Thomas W. Miihleisen, Peter Pp Pramstaller

, Paterson Ad, Terho J. Lehtimäki, Andrew D. Paterson, Afshin Parsa, van Duijn Cm, Yongmei Liu, C. M. Van Duijn, Siscovick Ds, David S. Siscovick, Vilmundur Gudnason, Yalda Jamshidi, Veikko Salomaa, Felix Sb, Stephan B. Felix, Serena Sanna

, Marylyn D. Ritchie

, Ritchie Md, Bruno H. Stricker, Stricker Bh, Kari Stefansson, Laurie A. Boyer, Boyer La, Thomas P. Cappola, Jesper V. Olsen, Cappola Tp, Stefan Kaab, Olsen Jv, Kasper Lage, Peter J. Schwartz, Schwartz Pj, Stefan Kääb, Aravinda Chakravarti, Michael J. Ackerman, Dcct Edic, Ackerman Mj, Arne Pfeufer, de Bakker Pi, Christopher Newton-Cheh, Stefan Kääb

Show less

This paper is made freely available by the publisher.

Full text: Download

Preprint: archiving allowed

Upload

Postprint: archiving restricted

Upload

Published version: archiving forbidden

Policy details

Data provided by

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. © 2014 Nature America, Inc.

Published in

Links

Tools

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Abstract