Causal role of immune cells on risk of Parkinson’s disease: a Mendelian randomization study

Abstract

Background: Previous observational studies have suggested a correlation between immune cells and Parkinson’s disease (PD), yet specific investigations into the causal relationship between the two remain limited. This study aims to explore this potential causal relationship. Methods: We utilized genome-wide association study (GWAS) data on immune cells and Parkinson’s Disease, conducting a two-sample Mendelian randomization (MR) analysis using single nucleotide polymorphisms (SNPs). To estimate causality, we employed inverse variance weighting (IVW), MR-Egger, and weighted median (WM) methods. For sensitivity analysis, we used Cochran’s Q-test, MR-Egger intercept, leave-one-out analysis, and funnel plots. Results: After false discovery rate (FDR) correction, the effects of PD on immune cells, and vice versa, were not statistically significant. These include CX3CR1 on CD14+ CD16-monocyte (OR = 0.91, 95% CI = 0.86–0.96, p = 0.0003 PFDR = 0.152), CD62L-CD86+ myeloid DC AC (OR = 0.93, 95% CI = 0.89–0.97, p = 0.0005, PFDR = 0.152),CD11b on Mo (OR = 1.08, 95% CI = 1.03–1.13, p = 0.001, PFDR = 0.152), CD38 on igd+ cd24− (OR = 1.14, 95% CI = 1.06–1.23, p = 0.001, PFDR = 0.152), D14+ cd16+ monocyte %monocyte (OR = 1.10, 95% CI = 1.04–1.17, p = 0.001, PFDR = 0.159). Additionally, PD may be causally related to the immune phenotype of CM CD8br %T cell (beta = 0.10, 95% CI = 1.14–1.16, p = 0.0004, PFDR = 0.151), SSC-A on monocyte (beta = 0.11, 95% CI = 1.15–1.18, p = 0.0004, PFDR = 0.1 SSC-A on monocyte). No pleiotropy was determined. Conclusion: This study suggested a potential causal link between immune cells and Parkinson’s Disease through the MR method, which could provide a new direction for the mechanistic research and clinical treatment of PD.