Job involvement in heavy manual or physical work associated with epigenetic age: A Mendelian randomization study

Engaging in heavy manual or physical work has been linked to various health outcomes, but its effect on physiological aging, as measured by epigenetic clocks, remains unclear. This study aims to analyze the causal relationship between heavy manual or physical work and epigenetic age acceleration using Mendelian randomization (MR). In this study, we explored the causal link between job involvement in heavy manual or physical work and epigenetic age acceleration measured by 4 different epigenetic clocks using 2-sample MR. Our analytical approach included inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode methods. The primary analyses utilized IVW with random effects, supplemented by sensitivity and heterogeneity tests using both IVW and MR-Egger. MR-Egger was also applied for pleiotropy testing. Additionally, a leave-one-out analysis helped identify potentially impactful single-nucleotide polymorphisms. The analysis revealed a positive association between heavy manual or physical work and epigenetic clock acceleration. There statistically significant associations between heavy manual or physical work with a higher PhenoAge and HannumAge acceleration (β = 1.692, 95% CI [0.349 to 3.035], P = .013 for PhenoAge; β = 0.917, 95% CI [0.024 to 1.809], P = .044 for HannumAge, respectively). The heterogeneity test revealed that our IVW analysis exhibited minimal heterogeneity (P > .05), and the pleiotropy test findings confirmed the absence of pleiotropy within our IVW analysis (P > .05). Our study provides partial evidence for a causal effect between heavy manual or physical work and epigenetic age acceleration. Further experimental research is required to confirm these findings.