Investigation of the causal relationship between cholelithiasis and Parkinson's disease: A bidirectional Mendelian randomization study

Background: Parkinson's disease (PD) and cholelithiasis are a huge public health burden. Although observational studies have suggested a potential link between PD and cholelithiasis, the causal relationship between the two remains uncertain. To address this gap, we performed a two-sample bidirectional Mendelian randomization analysis using genetic tools. Method: Genome-wide association study summary statistics for all traits were obtained from publicly available databases. We used strict control steps in instrumental variable selection to screen for single nucleotide polymorphisms (SNPs) from summary-level genome-wide association studies. In addition, all F-statistics were >10, indicating no weak instrumental bias. The inverse variance weighting (IVW) method was the primary method used to assess causal associations. Four other MR methods (MR-Egger, Weighted Median, Simple mode, and Weighted mode) were also used to complement IVW. Various sensitivity tests were also performed to assess reliability: (1) Cochrane's Q test for assessing heterogeneity, (2) MR-Egger intercept test and MR-PRESSO global test for assessing horizontal multiplicity, and (3) leave-one-out sensitivity test for determining stability. Results: We selected a total of 30 SNPs as instrumental variables. It was demonstrated that cholelithiasis had a causal effect on the risk of PD (OR = 1.146, 95% CI: 1.062-1.236, p < 0.001) in IVW method. Conclusion: The results of our analysis revealed an increased risk effect of cholelithiasis against PD, which may give light on new approaches to PD prevention and therapy.