Causal effects of socioeconomic traits on frailty: a Mendelian randomization study

The relationship between socioeconomic status and frailty has been extensively investigated in the literature, but it remains unclear whether a causal relationship exists. Our goal is to evaluate the causal relationship between six socioeconomic traits and the frailty index using summary-level data for single nucleotide polymorphisms from large genome-wide association studies with individuals of European ancestry.

A two-sample MR was performed. We applied the inverse variance weighted (IVW) method for the primary estimate, with sensitivity analyses conducted using alternative MR methods to evaluate the robustness of the findings. A subsequent multivariable MR was undertaken to adjust for the effects of body mass index (BMI). Finally, the MR Steiger directionality test was performed to confirm the causal direction.

The IVW MR analysis revealed significant associations between various socioeconomic factors and the frailty index. Specifically, genetically predicated age completed full time education (β = -0.477, 95% confidence interval [CI]: -0.634 to -0.319) and average total household income before tax (β = -0.321, 95% CI: -0.410 to -0.232) were negatively associated with the frailty index. On the other hand, genetically predicted job involves heavy manual or physical work (β = 0.298, 95% CI: 0.113 to 0.484), job involves mainly walking or standing (β = 0.179, 95% CI: 0.013 to 0.345), Townsend deprivation index at recruitment (β = 0.535, 95% CI: 0.285 to 0.785), and social isolation/loneliness (β = 1.344, 95% CI: 0.834 to 1.853) were positively associated with the frailty index. Sensitivity analysis using other MR methods and multivariable MR analysis adjusting for BMI yielded stable results. The MR Steiger directionality test confirmed the causal direction.

Our findings highlight the importance of socioeconomic factors in affecting frailty risk. Future research should focus on unraveling the pathways through which these socioeconomic factors exert their effects on frailty, with the ultimate goal of developing targeted strategies to mitigate the risk of frailty.