To identify genetic factors influencing cardiac conduction, we carried out a genome-wide association study of electrocardiographic time intervals in 6,543 Indian Asians. We identified association of a nonsynonymous SNP, rs6795970, in SCN10A (P = 2.8 x 10 15) with PR interval, a marker of cardiac atrioventricular conduction. Replication testing among 6,243 Indian Asians and 5,370 Europeans confirmed that rs6795970 (GA) is associated with prolonged cardiac conduction (longer P-wave duration, PR interval and QRS duration, P = 10 5 to 10 20). SCN10A encodes Na V 1.8, a sodium channel. We show that SCN10A is expressed in mouse and human heart tissue and that PR interval is shorter in Scn10a / mice than in wild-type mice. We also find that rs6795970 is associated with a higher risk of heart block (P 0.05) and a lower risk of ventricular fibrillation (P = 0.01). Our findings provide new insight into the pathogenesis of cardiac conduction, heart block and ventricular fibrillation. 2010 Nature America, Inc. All rights reserved.
CITATION STYLE
J.C., C., J., Z., C.M.N., T., C.R., B., W., Z., R., K., … J.S., K. (2010). Genetic variation in SCN10A influences cardiac conduction. Nature Genetics. J. C. Chambers, Department of Epidemiology and Public Health, Imperial College London, London, United Kingdom. E-mail: john.chambers@ic.ac.uk: Nature Publishing Group (345 Park Avenue South, New York NY 10010-1707, United States). Retrieved from http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed9&NEWS=N&AN=2010082801
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