Objective: To examine the causal link between peripheral immune cell traits and Parkinson’s disease (PD) risk.

Background: Observational studies have highlighted an association between peripheral immune cells and PD, suggesting potential immunological contributions to the disease pathology.

Method: We conducted a two-sample Mendelian randomization (MR) study using GWAS data to assess the link between immune cell traits and PD risk. This involved a rigorous selection of instrumental variables and was complemented by multivariable Mendelian Randomization (MVMR) analysis and validation in the PD age at onset (AAO) database.

Results: We identified four blood immune-cell-related traits that have a causal effect on PD risk. One trait was found to increase PD risk: CD3 on CD45RA⁺ CD4⁺ T cells (odds ratio [OR] and 95% confidence interval [CI] = 1.05 (1.04–1.06), P = 4.38E-28). The other three traits were found to decrease PD risk: 1) the percentage of T lymphocytes predominantly expressing CD45RO⁺ CD4⁺ CD25⁺ CD127^hi (OR [95% CI] = 0.93 (0.91–0.95), P = 6.19E-11); 2) CD64 on CD14⁺ CD16^– monocyte (OR [95% CI] = 0.85 (0.79–0.92), P = 4.36E-05); 3) CD64 on monocyte (OR [95% CI] = 0.84 (0.78–0.91), P = 2.08E-05). All the above results passed the Bonferroni correction and all sensitivity tests. Furthermore, these findings were also well validated in MVMR analysis and supported in the PD AAO database.

Conclusion: Our study underscores the correlation between peripheral immune cell traits and the risk of PD, providing insights into the relationship between peripheral immunity and PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/immune-cell-traits-and-parkinsons-disease-a-mendelian-randomization-study/