Zhao Yating, Zhang Xiaoqian, Guo Na, Tian Dandan, Zhang Chenguang, Mu Changqing, Han Chen, Zhu Ruixia, Zhang Jian, Liu Xu
Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, China.
Key Laboratory of Cell Biology, Ministry of Public Health, Department of Cell Biology, China Medical University, Shenyang, China.
Front Aging Neurosci. 2022 Mar 1;14:811059. doi: 10.3389/fnagi.2022.811059. eCollection 2022.
Parkinson's disease (PD) is widely considered to be a disabling neurodegenerative disorder, which has been ranked second worldwide just after Alzheimer's disease. Until present, a wide range of studies has focused on the role of circulating inflammatory cytokines in the development of PD. However, the causal relationship between circulating inflammatory cytokines and the risk and age at the onset of PD has not been elucidated. Hence, to evaluate the effects of circulating inflammatory cytokines on the risk or age at the onset of PD more accurately, we conducted this two-sample Mendelian randomization (MR) study involving summary statistics from genome-wide association studies (GWASs). Totally, we included a GWAS for inflammatory cytokines (8,293 participants), a meta-analysis of GWASs for PD risk (482,730 participants), and a GWAS dataset for age at the onset of PD (17,996 patients with PD). A total of 149 and 131 polymorphisms for exploring relationships between 19 inflammatory cytokines and the risk and age at the onset of PD were obtained as instrumental variants. Then, we used a total of five MR methods, including inverse-variance weighted (IVW), Wald ratio, MR Egger regression, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Finally, we found a causal association between circulating levels of macrophage inflammatory protein-1 beta (MIP1b) and PD risk in the IVW method (OR: 1.06; 95% CI: 1.02-1.10; = 0.001). Meanwhile, other MR estimates by weighted median and MR-PRESSO methods yielded similar effect estimates. Besides, we identified a suggestive association of interleukin-16 (IL-16) levels with PD risk (OR: 1.08; 95% CI: 1.00-1.17; = 0.037). For age at PD onset, there was no evidence supporting its correlation with inflammatory cytokines. Our findings implied that MIP1b and IL-16 may be novel biomarkers and promising therapeutic targets for PD development.
帕金森病（PD）被广泛认为是一种致残性神经退行性疾病，在全球范围内仅次于阿尔茨海默病，排名第二。到目前为止，大量研究聚焦于循环炎症细胞因子在PD发病过程中的作用。然而，循环炎症细胞因子与PD发病风险及发病年龄之间的因果关系尚未阐明。因此，为了更准确地评估循环炎症细胞因子对PD发病风险或发病年龄的影响，我们开展了这项两样本孟德尔随机化（MR）研究，该研究纳入了全基因组关联研究（GWAS）的汇总统计数据。我们总共纳入了一项炎症细胞因子的GWAS（8293名参与者）、一项PD风险的GWAS荟萃分析（482730名参与者）以及一项PD发病年龄的GWAS数据集（17996名PD患者）。共获得149个和131个多态性位点作为工具变量，用于探索19种炎症细胞因子与PD发病风险及发病年龄之间的关系。然后，我们总共使用了五种MR方法，包括逆方差加权（IVW）、Wald比、MR-Egger回归、加权中位数和MR-多效性残差和异常值（MR-PRESSO）方法。最后，我们在IVW方法中发现循环巨噬细胞炎性蛋白-1β（MIP1b）水平与PD风险之间存在因果关联（比值比：1.06；95%置信区间：1.02-1.10；P = 0.001）。同时，加权中位数和MR-PRESSO方法的其他MR估计得出了相似的效应估计值。此外，我们发现白细胞介素-16（IL-16）水平与PD风险存在提示性关联（比值比：1.08；95%置信区间：1.
