Association between inflammatory bowel disease and Parkinson’s disease: A Mendelian randomization study

Emerging evidence from observational studies suggests an increased risk of Parkinson’s disease (PD) in patients with inflammatory bowel disease (IBD). However, to date it is not clear whether a causal relationship exists. To investigate whether IBD is causally related to PD, a two-sample Mendelian randomization study was carried out. Independent genetic instruments from the largest available genome-wide association study (GWAS) for IBD (7045 cases, 456,327 controls) including European participants were used to investigate the association with PD (56,306 cases; 1.4 million controls). The results were validated by using a second IBD sample (12,882 cases; 21,770 controls) including the main subtypes ulcerative colitis (UC; 6968 cases; 20,464 controls) and Crohn’s disease (CD; 5956 cases; 14,927 controls). The radial inverse-variance weighted (IVW) approach was used in the primary analysis, and the robustness of the findings were confirmed in a number of sensitivity analyses. Finally, the recently proposed CAUSE approach was performed. There was no evidence of an association between IBD and PD (OR(IVW) = 0.98; 95% CI: [0.93; 1.04]; P = 0.48). This finding could be validated using a second sample of IBD cases (OR(IVW) = 0.98; 95% CI: [0.95; 1.02]; P = 0.36). Furthermore, MR analyses did not support a causal effect of CD (OR(IVW) = 1.00; 95% CI: [0.98; 1.03]; P = 0.96) or UC (OR(IVW) = 1.02; 95% CI: [0.98; 1.06]; P = 0.45) on PD. The present study suggests that neither IBD nor its subtypes CD and UC causally affect Parkinson’s disease in the European population. Further research is necessary to investigate whether intestinal inflammation impacts the development of PD.