Sarcopenia and depression are common and often coexist in the elderly. This study aims to determine the impact of sarcopenia-related muscle traits on depression.A two-sample Mendelian randomization (MR) study was performed on the summary-level data from the FinnGen cohort to estimate the causal association of appendicular lean mass (ALM), walking pace, or low hand grip strength with depression. Additionally, multivariable MR (MVMR) was performed to assess the dependence of each muscle trait in the causality and adjust the effect of body mass index (BMI). Supplementary backward MR analyses were performed to estimate the effect of depression on sarcopenia-related muscle traits.Univariable MR analyses demonstrated that there were causal associations of ALM (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.88-0.99), walking pace (OR: 0.53; 95% CI: 0.32-0.88), and low hand grip strength (OR: 1.20; 95% CI: 1.05-1.38) with depression. MVMR analyses showed that ALM was the only trait that had a significant causal relationship with depression (OR: 0.91; 95% CI: 0.85-0.98) after accounting for the other two muscle traits. Moreover, the independent association of ALM with depression remained (OR: 0.92; 95% CI: 0.85-0.99) after being adjusted by BMI. The backward MR analyses showed no causal associations of depression with any sarcopenia-related muscle traits.Low muscle mass independently increases the risk of depression. This study determined the muscle-related risk factors of depression, which may help establish the causality between sarcopenia and depression and provide evidence-based recommendations for improving mental health in the elderly.Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.