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

Sotoodehnia, N. et al. (2010) Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction. Nature Genetics, 42(12), pp. 1068-1076. (doi: 10.1038/ng.716)

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 genomewide 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 x 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna
• 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., and Arking, D.E.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences
• Journal Name: Nature Genetics
• ISSN: 1061-4036