Association between epigenetic aging and atrioventricular block: a two-sample Mendelian randomization study

Atrioventricular block (AVB) is a prevalent bradyarrhythmia. This study aims to investigate the causal effects of epigenetic aging, as inferred from DNA methylation profiles on the prevalence of AVB by Mendelian randomization (MR) analysis.

Genetic instruments for epigenetic aging and AVB were obtained from genome-wide association study data in the Edinburgh DataShare and FinnGen biobanks. Univariable and multivariable MR analyses were conducted to evaluate causal associations. Additionally, we employed sensitivity tests to assess the robustness of the MR findings.

MR analysis showed that genetically predicted GrimAge acceleration was significantly associated with a higher risk of AVB (inverse variance-weighted: p = 0.010, 95% confidence interval (CI) = 1.024-1.196; weighted median: p = 0.031, 95% CI = 1.009-1.215). However, no evidence supported a causal relationship between AVB and epigenetic aging. The association between epigenetic aging and AVB was established using multivariate MR analysis after adjusting for various risk factors. Sensitivity analyses confirmed the reliability and robustness of the results.

Our findings suggest that epigenetic aging in GrimAge may increase the risk of AVB, emphasizing the importance of addressing epigenetic aging in strategies for AVB prevention.