Exploring causality between educational attainment and frailty: A Mendelian randomization and mediation analysis

As a key marker of socioeconomic standing, educational attainment (EA) has been implicated in multiple disease processes. Nevertheless, the extent to which EA causally contributes to frailty is still uncertain. This study sought to investigate whether EA exerts a causal influence on frailty and to explore the mediating roles of related risk factors. A Mendelian randomization analysis was performed to evaluate the potential relationship between EA and frailty. Two frailty-related phenotypes, the frailty index and frailty phenotype, were selected as the primary outcomes. Two frailty-related traits were additionally selected as secondary outcomes, and including walking pace and physical inactivity. Multivariable Mendelian randomization was used to assess the mediating effects of smoking and BMI on the relationship between educational attainment and frailty. The results provided evidence that higher educational attainment was significantly associated with a lower risk of frailty. Specifically, this genetic predisposition corresponded to 25.8% reduction in frailty index, 22.2% decrease in frailty phenotype, 21.1% increase in walking speed, and 65.6% increase in physical activity intensity. Sensitivity analyses further confirmed the robustness and reliability of these causal estimates. The Multivariable Mendelian randomization analysis demonstrated the effects of educational attainment on cigarettes per day and BMI. Smoking and BMI, as potential risk factors, may mediate the causal relationship between EA and frailty. A higher level of EA provides a protective effect against the risk of frailty. We found that this association may be mediated by smoking and BMI, suggesting that reducing smoking and BMI could be effective measures for preventing frailty due to low educational attainment.