Common variants at ten loci influence myocardial repolarization: the QTGEN consortium

QT interval duration reflecting myocardial repolarization on the electrocardiogram is a heritable risk factor for sudden cardiac death and drug-induced arrhythmias. We conducted a meta-analysis of 3 genome-wide association studies in 13,685 individuals of European ancestry from the Framingham Heart Study, the Rotterdam Study and the Cardiovascular Health Study. We observed associations at P < 5×10(−8) with variants in NOS1AP, KCNQ1, KCNE1, KCNH2 and SCN5A, known to be involved in myocardial repolarization and Mendelian Long QT Syndromes. Associations at five novel loci included 16q21 near NDRG4 and GINS3, 6q22 near PLN, 1p36 near RNF207, 16p13 near LITAF and 17q12 near LIG3 and RIFFL. Collectively, the 14 independent variants at these 10 loci explain 5.4–6.5% of variation in QT interval. Identifying the causal variants and defining their impact on myocardial repolarization may add incrementally to the prevention of sudden cardiac death and drug-induced arrhythmias.