Subjective sleep problems is associated with epigenetic age acceleration: a Mendelian randomization study

Abstract Objective To investigate the potential causal associations between 3 common subjective sleep problems, daytime sleepiness, insomnia, and sleep apnea, and epigenetic age acceleration. Methods A two-sample Mendelian randomization (MR) study was conducted the publicly available genome-wide association study (GWAS) data to assess the causal effects of self-reported sleep problems on 4 indicators of epigenetic age acceleration, including intrinsic epigenetic age acceleration (IEAA), GrimAge acceleration, HannumAge acceleration, and PhenoAge acceleration. The primary analytical method was inverse-variance weighting (IVW), supplemented by sensitivity analyses using MR-Egger regression and the weighted median (WM) method to examine the robustness of the findings. Results IVW showed that daytime sleepiness was significantly positively associated with IEAA (β=1.83, 95%CI: 0.17~2.49, P=0.031) and HannumAge acceleration (β=1.81, 95%CI: 0.21~2.42, P=0.027), suggesting a potential accelerating effect on epigenetic aging. Insomnia also showed significant positive associations with IEAA (β=1.57, 95%CI: 0.40~2.73, P=0.009) and GrimAge acceleration (β=1.37, 95%CI: 0.18~2.56, P=0.024). No significant causal relationship was observed between sleep apnea and any indicator of epigenetic age acceleration (P>0.05). Conclusion Daytime sleepiness and insomnia may accelerate epigenetic aging, indicating their potential biological role in the aging process. The impact of sleep apnea remains unclear and warrants further investigation.