The narrow-sense and common single nucleotide polymorphism heritability of early repolarization

Background Early repolarization (ER) is a risk marker for sudden cardiac death. Higher risk is associated with horizontal/descending ST-segment ER in the inferior or inferolateral ECG leads. Studies in family cohorts have demonstrated substantial heritability for the ER pattern, but genome-wide association studies (GWAS) have failed to identify statistically significant and replicable genetic signals. Methods and results We assessed the narrow-sense and common single nucleotide polymorphism (SNP) heritability of ER and ER subtypes using ECG data from 5829 individuals (TwinsUK, BRIGHT and GRAPHIC cohorts). ER prevalence was 8.3%. In 455 monozygous vs 808 dizygous twin pairs, concordances and twin correlations for ER subtypes (except horizontal/descending ST-segment ER) were higher and familial resemblance (except notched ER) was significant. Narrow-sense heritability estimates derived from 1263 female twin pairs using the structural equation program Mx ranged from 0.00–0.47 and common SNP heritability estimates derived from 4009 unrelated individuals of both sexes using Genome-wide Restricted Maximum Likelihood (GREML) ranged from 0.00–0.36, but none were statistically significant. Conclusion From our data, ER shows limited genetic predisposition. There appears to be significant environmental influence and these modest narrow-sense and common SNP heritability estimates may explain why previous GWAS have been unsuccessful.