Genetic variation in SCN10A influences cardiac conduction

Abstract

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 × 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.