No Bidirectional Causal Relationship Between Traumatic Brain Injury and Parkinson's Disease: A Two-Sample Mendelian Randomization Study

Background: The incidence of Parkinson's disease (PD) is significantly increased in older people who have experienced traumatic brain injury (TBI), suggesting that TBI may be a potential risk factor for PD. However, the causal relationship remains ambiguous. Objective: To investigate the association between TBI and PD using Mendelian randomization (MR) analyses. Methods: Four genome-wide association databases were reviewed in detail, including GWAS Catalog, FinnGen, IEU OpenGWAS, and UK Biobank. Genetic data for TBI were obtained from the FinnGen data set, including 7430 clinically diagnosed cases and 404,751 controls, and PD was obtained from a meta-analysis in the GWAS Catalog, including 42,792 cases and 568,693 controls. The bidirectional two-sample MR analyses were used to investigate the causal association between TBI and PD. Results: There was no evidence of a causal relationship between TBI and an increased risk of PD (IVW; OR = 1.11; 95% CI, 0.91-1.36; p = 0.308). Similarly, genetically predisposed PD was not associated with a high risk of TBI (IVW; OR = 0.96; 95% CI, 0.91-1.02; p = 0.209). Results from MR-Egger regression, weighted mode, and weighted median analyses were consistent with those from the IVW analysis. Additional sensitivity analyses further supported the robustness of our conclusions. Conclusions: No causal relationship was found between TBI and PD.