BackgroundPrevious 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.MethodsWe 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.ResultsAfter 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.ConclusionThis 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.

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免疫细胞与帕金森病风险的因果作用：孟德尔随机研究

背景先前的观察性研究表明免疫细胞与帕金森病（PD）之间存在相关性，但对两者之间因果关系的具体研究仍然有限。本研究旨在探索这种潜在的因果关系。方法我们利用免疫细胞和帕金森病的全基因组关联研究 (GWAS) 数据，使用单核苷酸多态性 (SNP) 进行两样本孟德尔随机化 (MR) 分析。为了估计因果关系，我们采用了逆方差加权 (IVW)、MR-Egger 和加权中值 (WM) 方法。对于敏感性分析，我们使用了 Cochran 的 Q 检验、MR-Egger 截距、留一分析和漏斗图。结果经过错误发现率 (FDR) 校正后，PD 对免疫细胞的影响，反之亦然。统计上显着。其中包括 CD14+ CD16 单核细胞上的 CX3CR1（OR = 0.91，95% CI = 0.86–0.96，p= 0.0003 PFDR = 0.152)，CD62L-CD86+ 骨髓 DC AC（OR = 0.93，95% CI = 0.89–0.97，p= 0.0005，PFDR = 0.152)，Mo 上的 CD11b（OR = 1.08，95% CI = 1.03–1.13，p= 0.001，PFDR = 0.152），igd+ cd24− 上的 CD38（OR = 1.14，95% CI = 1.06–1.23，p= 0.001，PFDR = 0.152)，D14+ cd16+ 单核细胞 % 单核细胞（OR = 1.10，95% CI = 1.04–1.17，p= 0.001，PFDR = 0.159）。此外，PD 可能与 CM CD8br %T 细胞的免疫表型有因果关系（β = 0.10，95% CI = 1.14–1.16，p= 0.0004，PFDR = 0.151），单核细胞上的 SSC-A（β = 0.11，95% CI = 1.15–1.18，p= 0.0004，单核细胞上的 PFDR = 0.1 SSC-A）。未确定多效性。结论本研究通过MR方法提示免疫细胞与帕金森病之间存在潜在的因果关系，为帕金森病的机制研究和临床治疗提供新的方向。