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Cited by 352

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction

Open access
Sotoodehnia, Nona, Isaacs, Aaron, de Bakker, Paul I W, Dörr, Marcus, Newton-Cheh, Christopher, Nolte, Ilja M, van der Harst, Pim, Müller, Martina, Eijgelsheim, Mark, Alonso, Alvaro, Hicks, Andrew A, Padmanabhan, Sandosh, Hayward, Caroline, Smith, Albert Vernon, Polasek, Ozren, Giovannone, Steven, Fu, Jingyuan, Magnani, Jared W, Marciante, Kristin D, Pfeufer, Arne, Gharib, Sina A, Teumer, Alexander, Li, Man, Bis, Joshua C, Rivadeneira, Fernando, Aspelund, Thor, Köttgen, Anna, Johnson, Toby, Rice, Kenneth, Sie, Mark P S, Wang, Ying A, Klopp, Norman, Fuchsberger, Christian, Wild, Sarah H, Leach, Irene Mateo, Estrada, Karol, Völker, Uwe, Wright, Alan F, Asselbergs, Folkert W, Qu, Jiaxiang, Chakravarti, Aravinda, Sinner, Moritz F, Kors, Jan A, Petersmann, Astrid, Harris, Tamara B, Soliman, Elsayed Z, Munroe, Patricia B, Psaty, Bruce M, Oostra, Ben A, Cupples, L Adrienne, Perz, Siegfried, de Boer, Rudolf A, Uitterlinden, André G, Völzke, Henry, Spector, Timothy D, Liu, Fang-Yu, Boerwinkle, Eric, Dominiczak, Anna F, Rotter, Jerome I, van Herpen, Gé, Levy, Daniel, Wichmann, H-Erich, van Gilst, Wiek H, Witteman, Jacqueline C M, Kroemer, Heyo K, Kao, W H Linda, Heckbert, Susan R, Meitinger, Thomas, Hofman, Albert, Campbell, Harry, Folsom, Aaron R, van Veldhuisen, Dirk J, Schwienbacher, Christine, O'Donnell, Christopher J, Volpato, Claudia Beu, Caulfield, Mark J, Connell, John M, Launer, Lenore, Lu, Xiaowen, Franke, Lude, Fehrmann, Rudolf S N, te Meerman, Gerard, Groen, Harry J M, Weersma, Rinse K, van den Berg, Leonard H, Wijmenga, Cisca, Ophoff, Roel A, Navis, Gerjan, Rudan, Igor, Snieder, Harold, Wilson, James F, Pramstaller, Peter P, Siscovick, David S, Wang, Thomas J, Gudnason, Vilmundur, van Duijn, Cornelia M, Felix, Stephan B, Fishman, Glenn I, Jamshidi, Yalda, Ch Stricker, Bruno H, Samani, Nilesh J, Kääb, Stefan, Arking, Dan E·2010·Nature Genetics
DOI 10.1038/ng.716
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Abstract

The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10−8). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction.

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Authors
Sotoodehnia, N., Isaacs, A., de Bakker, P. I. W., Dörr, M., Newton-Cheh, C., Nolte, I. M., van der Harst, P., Müller, M., Eijgelsheim, M., Alonso, A., Hicks, A. A., Padmanabhan, S., Hayward, C., Smith, A. V., Polasek, O., Giovannone, S., Fu, J., Magnani, J. W., Marciante, K. D., Pfeufer, A., Gharib, S. A., Teumer, A., Li, M., Bis, J. C., Rivadeneira, F., Aspelund, T., Köttgen, A., Johnson, T., Rice, K., Sie, M. P. S., Wang, Y. A., Klopp, N., Fuchsberger, C., Wild, S. H., Leach, I. M., Estrada, K., Völker, U., Wright, A. F., Asselbergs, F. W., Qu, J., Chakravarti, A., Sinner, M. F., Kors, J. A., Petersmann, A., Harris, T. B., Soliman, E. Z., Munroe, P. B., Psaty, B. M., Oostra, B. A., Cupples, L. A., Perz, S., de Boer, R. A., Uitterlinden, A. G., Völzke, H., Spector, T. D., Liu, F.-Y., Boerwinkle, E., Dominiczak, A. F., Rotter, J. I., van Herpen, G., Levy, D., Wichmann, H.-E., van Gilst, W. H., Witteman, J. C. M., Kroemer, H. K., Kao, W. H. L., Heckbert, S. R., Meitinger, T., Hofman, A., Campbell, H., Folsom, A. R., van Veldhuisen, D. J., Schwienbacher, C., O'Donnell, C. J., Volpato, C. B., Caulfield, M. J., Connell, J. M., Launer, L., Lu, X., Franke, L., Fehrmann, R. S. N., te Meerman, G., Groen, H. J. M., Weersma, R. K., van den Berg, L. H., Wijmenga, C., Ophoff, R. A., Navis, G., Rudan, I., Snieder, H., Wilson, J. F., Pramstaller, P. P., Siscovick, D. S., Wang, T. J., Gudnason, V., van Duijn, C. M., Felix, S. B., Fishman, G. I., Jamshidi, Y., Ch Stricker, B. H., Samani, N. J., Kääb, S., & Arking, D. E.
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2010-11-14
Volume
42
Issue
12
Pages
1068-1076
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.716
OpenAlex
W2164468497
Cited by
352
References
5
FWCI
18.80
Type
journal article
Language
en
Open access
green

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