Depression and sarcopenia-related traits: A Mendelian randomization study

Observational studies have suggested that depression is associated with sarcopenia. However, the causal relationship between depression and sarcopenia remains unclear.

To investigate the causal relationship between depression and sarcopenia.

We performed a Mendelian randomization (MR) analysis to identify the bidirectional relationship between depression and sarcopenia-related traits. Summary-level data and independent variants used as instrumental variables came from large genome-wide association studies of depression (414055 cases and 892299 controls), of appendicular lean mass (ALM, 450243 participants), and of hand grip strength (exposure: 360000 participants; outcome: 334925 participants).

We identified a negative association of depression with lower ALM [odds ratio (OR): 0.932, 95% confidence interval (95%CI): 0.889-0.979, P = 0.005]. In the reverse MR analysis, we also observed an inverse association of hand grip strength with depression (OR: 0.200, 95%CI: 0.108-0.370, P < 0.001). Similar results were obtained in sensitivity analyses.

Depression was causally related to decreased muscle mass, and declined muscle strength might lead to a higher risk of depression.