Mendelian randomization analysis reveals causal links between specific immune cell phenotypes and Parkinson's disease.

OBJECTIVE: Immunity and neuroinflammation are key factors in Parkinson's Disease (PD); however, detailed studies on how they are causally related to each other are lacking. This study aimed to explore the potential causal relationship between immune cells and PD. METHODS: A comprehensive two-sample Mendelian Randomization (MR) analysis was conducted based on publicly available genetic data to explore the causal relationship between 731 immune cells and PD risk. Inverse Variance Weighted (IVW) served as the main technique to explore the causal relationship, along with methods such as weighted median, MR-Egger regression, simple mode, and weighted mode. Sensitivity analysis was performed to evaluate the reliability, heterogeneity, and horizontal pleiotropy of the study results. RESULTS: A total of 18 immune cell phenotypes related to PD were identified in MR analysis, with 8 associated with risk, including 3 from the T-cells, B-cells, and Natural Killer cells (TBNK) group, 3 from the regulatory T-cell (Treg) group, and 2 from the myeloid group. There were 10 factors conferring protection against PD, with 3 associated with monocytes, 3 associated with T-cell maturation, 2 associated with Tregs, and 1 associated with myeloid cells. PD altered the phenotypic levels of two immune cell types, one from the TBNK group and one from the B-cell group. CONCLUSIONS: This study suggests a potential causal link between immune cells and PD, pinpointing specific immune cell features related to PD.