In-depth Analysis of Risk Factors in Parkinson's Disease: Insights from Mendelian Randomization Studies

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Abstract Background The incidence and prevalence of Parkinson's disease (PD) are rapidly increasing, leading to significant disease and economic burden. Identifying causal relationships, exposures, risk factors, and molecular processes associated with the occurrence and progression of PD is crucial for the development of prevention and treatment strategies. Methods In this systematic review, we examined evidence regarding causal associations between potential risk factors and PD derived from Mendelian randomization (MR) studies, adhering to PRISMA guidelines. Methodological quality was evaluated based on critical components of MR methodology, including comprehensive instrumental variable analysis and validation of the three key MR assumptions. Results We included methodological details and findings from 41 articles. MR studies provided evidence for causal relationships between BMI, lifestyle, lipid levels, AD, stroke, anxiety, depression, inflammatory bowel disease, rheumatoid arthritis, and PD, although results varied substantially across each category. Conclusions Although this review demonstrates how MR can offer valuable insights into exploring potential therapeutic targets and enhancing our understanding of the pathophysiology of PD, certain methodological limitations in the existing literature hinder the reliability of results and likely contribute to their heterogeneity. We emphasize the importance of future MR studies focusing on lifestyle factors, gut microbiota, and epigenetics.

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