Genetically Predicted Levels of Circulating Inflammatory Cytokines and the Risk and Age at Onset of Parkinson's Disease: A Two-Sample Mendelian Randomization Study

Yating Zhao; Xiaoqian Zhang; Na Guo; Dandan Tian; Chenguang Zhang; Changqing Mu; Chen Han; Ruixia Zhu; Jian Zhang; Xu Liu

doi:10.3389/fnagi.2022.811059

Genetically Predicted Levels of Circulating Inflammatory Cytokines and the Risk and Age at Onset of Parkinson's Disease: A Two-Sample Mendelian Randomization Study

Front Aging Neurosci. 2022 Mar 1:14:811059. doi: 10.3389/fnagi.2022.811059. eCollection 2022.

Authors

Yating Zhao¹, Xiaoqian Zhang¹, Na Guo¹, Dandan Tian¹, Chenguang Zhang¹, Changqing Mu¹, Chen Han¹, Ruixia Zhu¹, Jian Zhang^{2

3}, Xu Liu¹

Affiliations

¹ Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, China.
² Key Laboratory of Cell Biology, Ministry of Public Health, Department of Cell Biology, China Medical University, Shenyang, China.
³ Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.

Abstract

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; P = 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; P = 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.

Keywords: Mendelian randomization; Parkinson’s disease; cytokines; inflammation; interleukin-16; macrophage inflammatory protein-1 beta.