Abstract
This study aimed to investigate the potential causal relationship between depression and Parkinson's disease (PD) using Mendelian randomization (MR). Summary statistics for depression and PD were obtained from 2 large-scale genome-wide association studies (GWAS) involving individuals of European ancestry. Independent genetic loci associated with depression and PD were identified as instrumental variables. The inverse variance weighting (IVW) approach was used as the primary method for causal inference, while MR-Egger and weighted median methods served as supplementary analyses to verify the robustness of the results. Heterogeneity tests, multiple validity checks, and leave-one-out sensitivity analyses were conducted to assess the reliability of the findings. The IVW analysis yielded an odds ratio of 1.44 (95% confidence interval: 1.001-2.077, P = .048), suggesting a potential causal relationship between depression and PD. No evidence of heterogeneity or horizontal pleiotropy was found, and sensitivity analyses confirmed the reliability of the results. This study applied 2-sample MR analysis to genetic data, revealing a causal link between depression and the development of PD. These findings highlight the importance of early screening and intervention for individuals with depression to reduce the risk of developing PD.