Heritability of Early RepolarizationClinical Perspective

Background— Early repolarization (ER), defined by J-point elevation in 12-lead ECG, was recently associated with increased risk for idiopathic ventricular fibrillation and cardiovascular mortality. The determinants of ER are unknown. We investigated its heritability in a large, family-based cohort. Methods and Results— The study sample comprised 1877 individuals from 505 white nuclear families representative of the British general population. Standard 12-lead ECGs were evaluated for the presence of ER, defined as J-point elevation of ≥0.1 mV in at least 2 adjacent inferior (II, III, and aVF) or anterolateral (I, aVL, and V4 through V6) leads. Narrow sense heritability estimates were computed adjusting for age, age2, and sex. The prevalence of ER was 7.7% (n=145) in the whole cohort, 5.9% (n=56) in parents, and 9.6% (n=89) in offspring. Heritability estimate for the presence of ER was calculated at h2=0.49 (standard error=0.14; P =2.7*10−4) and was higher when restricted to its presence in inferior leads (h2=0.61, standard error=0.18, P =4.3*10−4) or for the notching ER morphology (h2=0.81, standard error=0.19, P =2.4*10−5). Individuals with at least 1 affected parent had a 2.5-fold increased risk for presenting with ER on ECG (odds ratio, 2.54; 95% confidence interval, 1.33 to 4.84; P =0.005). Familial transmission was more frequent when the mother was affected (odds ratio, 3.84; 95% confidence interval, 1.41 to 10.43; P =0.008) than when the father was affected (odds ratio, 1.82; 95% confidence interval, 0.82 to 4.03; P =0.141), although this difference was not statistically significant ( P =0.18). Conclusions— ER is a heritable phenotype. Offspring of ER-positive parents have a 2.5-fold increased risk of presenting with ER on their ECG.