广西医学

目的利用孟德尔随机化（MR）法分析免疫细胞特征与神经退行性疾病［（阿尔茨海默病（AD）、帕金森病（PD）和多发性硬化症（MS）］的关系。方法分别从GWAS Catalog数据库、IEU OpenGWAS Project数据库获取731种免疫细胞特征及AD、PD、MS的基因组关联研究数据。以731种免疫细胞特征作为暴露因素，以AD、PD 和MS作为结局，以与免疫细胞特征相关的单核苷酸多态性（SNP）作为工具变量，筛选工具变量后，采用逆方差加权（IVW）法作为主要方法，采用加权中位数法、MR⁃Egger 检验、简单模式法和加权模式法进行补充，进行两样本MR分析，并采用MR⁃Egger截距测试、Cochran′s Q检验、留一法进行敏感性分析。结果 IVW法分析结果显示，CD4+ CD8dim %leukocyte、CD4+ CD8dim %lymphocyte、CD4+ CD8dim AC、CD8 on CM CD8br、CD8 on naive CD8br、CD20 on memory B cell是AD发生的危险因素（OR>1，P<0.05）；B cell AC、CX3CR1 on CD14+ CD16- monocyte、Myeloid DC %DC是PD发生的保护因素（OR<1，P<0.05），CD11b on Mo MDSC是PD发生的危险因素（OR>1，P<0.05）；CM CD8br %T cell、CM CD8br AC、Myeloid DC AC是MS发生的保护因素（OR<1，P<0.05）。其余4种方法的分析结果与IVW法的结果一致。MR⁃Egger截距测试未发现水平多效性，Cochran's Q检验未发现异质性（P>0.05）。留一法结果显示，免疫细胞特征与AD、PD、MS之间的因果效应未受任一单个SNP的影响。结论 CD8+ T淋巴细胞水平的升高与AD和MS发病风险增加有关，其可能是这两种疾病的共同影响途径。Myeloid DC是MS的保护因素，亦是PD的危险因素。

Objective To analyze the relation of immune cell characteristics with neurodegenerative diseases with respect to Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) by employing the Mendelian randomization (MR) method. Methods A total of 731 immune cell characteristics and data of genome⁃wide association study of AD, PD, and MS were obtained from the databases of GWAS Catalog and IEU OpenGWAS Project, respectively. A total of 731 immune cell characteristics were used as exposure factors, AD, PD and MS were used as outcomes, and single nucleotide polymorphism (SNP) related to immune cell characteristics was used as instrumental variable, after screening instrumental variable, the inverse variance weighted (IVW) method was used as the main method, and then the weighted median method, MR⁃Egger test, simple mode method, and weighted mode method were used as supplement to perform the two⁃sample MR analysis; in addition, sensitivity analysis was performed by using the MR⁃Egger intercept test, Cochran's Q test, and leave⁃one⁃out method. Results The analytic results of IVW method revealed that CD4+ CD8dim %leukocyte, CD4+ CD8dim %lymphocyte, CD4+ CD8dim AC, CD8 on CM CD8br, CD8 on naive CD8br, and CD20 on memory B cell were the risk factors for the occurrence of AD (OR>1, P<0.05), whereas B cell AC, CX3CR1 on CD14+ CD16⁃ monocyte, and Myeloid DC %DC were the protective factors for the occurrence of PD (OR<1, P<0.05), and CD11b on Mo MDSC was the risk factor for the occurrence of PD (OR>1, P<0.05); in addition, CM CD8br %T cell, CM CD8br AC, and Myeloid DC AC were the protective factors for the occurrence of MS (OR<1, P<0.05). The analytic results of the remaining four methods were consistent with those of the IVW method. The MR⁃Egger intercept test did not find horizontal pleiotropy, while the Cochran's Q test did not find heterogeneity (P>0.05). The results of leave⁃one⁃out method indicated that the causal effect between immune cell characteristics and AD, PD, and MS was not affected by any single SNP. Conclusion The elevated level of CD8+ T lymphocyte is associated with the increased morbidity risk of AD and MS, which may be the common influence path of these two diseases. Myeloid DC is a protective factor for MS while a risk factor for PD.