Peripheral immune cell traits and Parkinson's disease: A Mendelian randomization study

PLoS One. 2024 Mar 5;19(3):e0299026. doi: 10.1371/journal.pone.0299026. eCollection 2024.

Abstract

Background: The peripheral immune system is altered in Parkinson's disease (PD), but the causal relationship between the two remains controversial. In this study, we aimed to estimate the causal relationship between peripheral immune features and PD using a two-sample Mendelian randomization (MR) approach.

Methods: Genome-wide association study (GWAS) data of peripheral blood immune signatures from European populations were used for exposure and PD summary statistics were used as results. We conducted a two-sample MR study using the inverse-variance weighted (IVW), MR-Egger, and weighted median methods to evaluate the causal association between these factors. MR-Egger and MR-PRESSO were used for sensitivity analysis to test and correct horizontal pleiotropy.

Results: A total of 731 immune traits were analyzed for association with PD using three MR methods. After adjustment for FDR, we observed four peripheral immunological features associated with PD using the IVW method, including expression of CX3CR1 on monocytes [OR: 0.85, 95% CI: (0.81, 0.91), P = 6.56E-07] and CX3CR1 on CD14+CD16+ monocytes [OR: 0.87, 95% CI: (0.82, 0.93), P = 9.95E-06].

Conclusions: Our study further revealed the important role of monocytes in PD and indicated that CX3CR1 expression on monocytes is associated with a reduced risk of PD.

MeSH terms

  • Genome-Wide Association Study*
  • Humans
  • Mendelian Randomization Analysis
  • Monocytes
  • Parkinson Disease* / genetics
  • Phenotype

Grants and funding

This work was supported by the Scientific and Technological Research Projects in Henan Province (grant number 222102310033) with funding received by author JT, the Key Research Project in Higher Education Institutions of Henan Province (grant number 22B320022) with funding received by author JT, and the National Natural Science Foundation of China (NSFC) (grant numbers 81974211 and 82171247) with funding received by author CS. There was no additional external funding received for this study.