Causality between sarcopenia-related traits and major depressive disorder: A bi-directional, two-sample Mendelian randomized study

Observational studies have demonstrated an association between sarcopenia and depression. However, these studies may be influenced by confounding factors, and the causal relationship between sarcopenia and major depressive disorder (MDD) remains unclear. This study aimed to apply the Mendelian randomization (MR) method to address confounding factors and assess the causal effect of sarcopenia on MDD. A two-way, two-sample MR method was employed in this study. Instrumental variables of genome-wide significance level were obtained from the open large-scale genome-wide association study summary data. MR analysis was conducted using inverse variance weighted, MR-Egger, and weighted median methods. The reliability of the results was verified using the heterogeneity test, pleiotropy test, and leave-one-out method for sensitivity analysis. Grip strength (right-hand grip strength: odds ratio [OR] = 0.880, 95% confidence interval [CI] 0.786-0.987, P = .027; left-hand grip strength: OR = 0.814, 95% CI 0.725-0.913, P < .001) and usual walking pace (OR = 0.673, 95% CI 0.506-0.896, P = .007) exhibited a direct causal effect on MDD. MDD had a significant causal effect on appendicular lean mass (beta = -0.065, 95% CI -0.110, -0.019, P = .005). There was a causal relationship between sarcopenia-related traits and MDD. Loss of muscle strength, rather than skeletal muscle mass, is correlated with an increased risk of MDD. Furthermore, individuals with MDD are more likely to experience loss of skeletal muscle mass.