Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization. Arking, D., Pulit, S., Crotti, L., Van Der Harst, P., Munroe, P., Koopmann, T., Sotoodehnia, N., Rossin, E., Morley, M., Wang, X., Johnson, A., Lundby, A., Gudbjartsson, D., Noseworthy, P., Eijgelsheim, M., Bradford, Y., Tarasov, K., Dörr, M., Müller-Nurasyid, M., Lahtinen, A., Nolte, I., Smith, A., Bis, J., Isaacs, A., Newhouse, S., Evans, D., Post, W., Waggott, D., Lyytikäinen, L., Hicks, A., Eisele, L., Ellinghaus, D., Hayward, C., Navarro, P., Ulivi, S., Tanaka, T., Tester, D., Chatel, S., Gustafsson, S., Kumari, M., Morris, R., Naluai, A., Padmanabhan, S., Kluttig, A., Strohmer, B., Panayiotou, A., Torres, M., Knoflach, M., Hubacek, J., Slowikowski, K., Raychaudhuri, S., Kumar, R., Harris, T., Launer, L., Shuldiner, A., Alonso, A., Bader, J., Ehret, G., Huang, H., Kao, W., Strait, J., Macfarlane, P., Brown, M., Caulfield, M., Samani, N., Kronenberg, F., Willeit, J., Smith, J., Greiser, K., Zu Schwabedissen, H., Werdan, K., Carella, M., Zelante, L., Heckbert, S., Psaty, B., Rotter, J., Kolcic, I., Polašek, O., Wright, A., Griffin, M., Daly, M., Arnar, D., Hólm, H., Thorsteinsdottir, U., Denny, J., Roden, D., Zuvich, R., Emilsson, V., Plump, A., Larson, M., O'Donnell, C., Yin, X., Bobbo, M., D'Adamo, A., Iorio, A., Sinagra, G., Carracedo, A., Cummings, S., Nalls, M., Jula, A., Kontula, K., Marjamaa, A., Oikarinen, L., Perola, M., Porthan, K., Erbel, R., Hoffmann, P., Jöckel, K., Kälsch, H., Nöthen, M., Den Hoed, M., Loos, R., Thelle, D., Gieger, C., Meitinger, T., Perz, S., Peters, A., Prucha, H., Sinner, M., Waldenberger, M., De Boer, R., Franke, L., Van Der Vleuten, P., Beckmann, B., Martens, E., Bardai, A., Hofman, N., Wilde, A., Behr, E., Dalageorgou, C., Giudicessi, J., Medeiros-Domingo, A., Barc, J., Kyndt, F., Probst, V., Ghidoni, A., Insolia, R., Hamilton, R., Scherer, S., Brandimarto, J., Margulies, K., Moravec, C., Del Greco M, F., Fuchsberger, C., O'Connell, J., Lee, W., Watt, G., Campbell, H., Wild, S., El Mokhtari, N., Frey, N., Asselbergs, F., Leach, I., Navis, G., Van Den Berg, M., Van Veldhuisen, D., Kellis, M., Krijthe, B., Franco, O., Hofman, A., Kors, J., Uitterlinden, A., Witteman, J., Kedenko, L., Lamina, C., Oostra, B., Abecasis, G., Lakatta, E., Mulas, A., Orrú, M., Schlessinger, D., Uda, M., Markus, M., Völker, U., Snieder, H., Spector, T., Ärnlöv, J., Lind, L., Sundström, J., Syvänen, A., Kivimaki, M., Kähönen, M., Mononen, N., Raitakari, O., Viikari, J., Adamkova, V., Kiechl, S., Brion, M., Nicolaides, A., Paulweber, B., Haerting, J., Dominiczak, A., Nyberg, F., Whincup, P., Hingorani, A., Schott, J., Bezzina, C., Ingelsson, E., Ferrucci, L., Gasparini, P., Wilson, J., Rudan, I., Franke, A., Mühleisen, T., Pramstaller, P., Lehtimäki, T., Paterson, A., Parsa, A., Liu, Y., Van Duijn, C., Siscovick, D., Gudnason, V., Jamshidi, Y., Salomaa, V., Felix, S., Sanna, S., Ritchie, M., Stricker, B., Stefansson, K., Boyer, L., Cappola, T., Olsen, J., Lage, K., Schwartz, P., Kääb, S., Chakravarti, A., Ackerman, M., Pfeufer, A., De Bakker, P., & Newton-Cheh, C. Nature Genetics, 2014.
abstract   bibtex   
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.
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 title = {Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization},
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 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.},
 bibtype = {article},
 author = {Arking, D.E. and Pulit, S.L. and Crotti, L. and Van Der Harst, P. and Munroe, P.B. and Koopmann, T.T. and Sotoodehnia, N. and Rossin, E.J. and Morley, M. and Wang, X. and Johnson, A.D. and Lundby, A. and Gudbjartsson, D.F. and Noseworthy, P.A. and Eijgelsheim, M. and Bradford, Y. and Tarasov, K.V. and Dörr, M. and Müller-Nurasyid, M. and Lahtinen, A.M. and Nolte, I.M. and Smith, A.V. and Bis, J.C. and Isaacs, A. and Newhouse, S.J. and Evans, D.S. and Post, W.S. and Waggott, D. and Lyytikäinen, L.-P. and Hicks, A.A. and Eisele, L. and Ellinghaus, D. and Hayward, C. and Navarro, P. and Ulivi, S. and Tanaka, T. and Tester, D.J. and Chatel, S. and Gustafsson, S. and Kumari, M. and Morris, R.W. and Naluai, A.T. and Padmanabhan, S. and Kluttig, A. and Strohmer, B. and Panayiotou, A.G. and Torres, M. and Knoflach, M. and Hubacek, J.A. and Slowikowski, K. and Raychaudhuri, S. and Kumar, R.D. and Harris, T.B. and Launer, L.J. and Shuldiner, A.R. and Alonso, A. and Bader, J.S. and Ehret, G. and Huang, H. and Kao, W.H.L. and Strait, J.B. and Macfarlane, P.W. and Brown, M. and Caulfield, M.J. and Samani, N.J. and Kronenberg, F. and Willeit, J. and Smith, J.G. and Greiser, K.H. and Zu Schwabedissen, H.M. and Werdan, K. and Carella, M. and Zelante, L. and Heckbert, S.R. and Psaty, B.M. and Rotter, J.I. and Kolcic, I. and Polašek, O. and Wright, A.F. and Griffin, M. and Daly, M.J. and Arnar, D.O. and Hólm, H. and Thorsteinsdottir, U. and Denny, J.C. and Roden, D.M. and Zuvich, R.L. and Emilsson, V. and Plump, A.S. and Larson, M.G. and O'Donnell, C.J. and Yin, X. and Bobbo, M. and D'Adamo, A.P. and Iorio, A. and Sinagra, G. and Carracedo, A. and Cummings, S.R. and Nalls, M.A. and Jula, A. and Kontula, K.K. and Marjamaa, A. and Oikarinen, L. and Perola, M. and Porthan, K. and Erbel, R. and Hoffmann, P. and Jöckel, K.-H. and Kälsch, H. and Nöthen, M.M. and Den Hoed, M. and Loos, R.J.F. and Thelle, D.S. and Gieger, C. and Meitinger, T. and Perz, S. and Peters, A. and Prucha, H. and Sinner, M.F. and Waldenberger, M. and De Boer, R.A. and Franke, L. and Van Der Vleuten, P.A. and Beckmann, B.M. and Martens, E. and Bardai, A. and Hofman, N. and Wilde, A.A.M. and Behr, E.R. and Dalageorgou, C. and Giudicessi, J.R. and Medeiros-Domingo, A. and Barc, J. and Kyndt, F. and Probst, V. and Ghidoni, A. and Insolia, R. and Hamilton, R.M. and Scherer, S.W. and Brandimarto, J. and Margulies, K. and Moravec, C.E. and Del Greco M, F. and Fuchsberger, C. and O'Connell, J.R. and Lee, W.K. and Watt, G.C.M. and Campbell, H. and Wild, S.H. and El Mokhtari, N.E. and Frey, N. and Asselbergs, F.W. and Leach, I.M. and Navis, G. and Van Den Berg, M.P. and Van Veldhuisen, D.J. and Kellis, M. and Krijthe, B.P. and Franco, O.H. and Hofman, A. and Kors, J.A. and Uitterlinden, A.G. and Witteman, J.C.M. and Kedenko, L. and Lamina, C. and Oostra, B.A. and Abecasis, G.R. and Lakatta, E.G. and Mulas, A. and Orrú, M. and Schlessinger, D. and Uda, M. and Markus, M.R.P. and Völker, U. and Snieder, H. and Spector, T.D. and Ärnlöv, J. and Lind, L. and Sundström, J. and Syvänen, A.-C. and Kivimaki, M. and Kähönen, M. and Mononen, N. and Raitakari, O.T. and Viikari, J.S. and Adamkova, V. and Kiechl, S. and Brion, M. and Nicolaides, A.N. and Paulweber, B. and Haerting, J. and Dominiczak, A.F. and Nyberg, F. and Whincup, P.H. and Hingorani, A.D. and Schott, J.-J. and Bezzina, C.R. and Ingelsson, E. and Ferrucci, L. and Gasparini, P. and Wilson, J.F. and Rudan, I. and Franke, A. and Mühleisen, T.W. and Pramstaller, P.P. and Lehtimäki, T.J. and Paterson, A.D. and Parsa, A. and Liu, Y. and Van Duijn, C.M. and Siscovick, D.S. and Gudnason, V. and Jamshidi, Y. and Salomaa, V. and Felix, S.B. and Sanna, S. and Ritchie, M.D. and Stricker, B.H. and Stefansson, K. and Boyer, L.A. and Cappola, T.P. and Olsen, J.V. and Lage, K. and Schwartz, P.J. and Kääb, S. and Chakravarti, A. and Ackerman, M.J. and Pfeufer, A. and De Bakker, P.I.W. and Newton-Cheh, C.},
 journal = {Nature Genetics},
 number = {8}
}

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