Association of immune cell traits with Parkinson's disease: a Mendelian randomization study

Zhiwei Song; Wangyu Li; Yupeng Han; Yiya Xu; Haiqi Ding; Yinzhou Wang

doi:10.3389/fnagi.2024.1340110

Association of immune cell traits with Parkinson's disease: a Mendelian randomization study

Front Aging Neurosci. 2024 Feb 22:16:1340110. doi: 10.3389/fnagi.2024.1340110. eCollection 2024.

Authors

Zhiwei Song¹, Wangyu Li², Yupeng Han³, Yiya Xu¹, Haiqi Ding⁴, Yinzhou Wang^{1

5}

Affiliations

¹ Department of Neurology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
² Department of Pain Management, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
³ Department of Anesthesiology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
⁴ Department of Orthopedic Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
⁵ Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China.

Abstract

Background: Immunity and neuroinflammation play crucial roles in the pathogenesis of Parkinson's disease (PD). Nonetheless, prior investigations into the correlation between immune inflammation and PD have produced varying results. Identifying specific immune cell phenotypes that are truly associated with PD is challenging, and the causal relationship between immune cells and PD remains elusive.

Methods: This study conducted a comprehensive two-sample Mendelian randomization (MR) analysis, employing five distinct analytical approaches, to clarify the causal connection between immune cell characteristics and the risk of PD. Utilizing GWAS data, we investigated the causal relationship between 731 immune cell traits and PD. These immune cell phenotypes encompass absolute cell (AC) counts, median fluorescence intensity (MFI), and relative cell (RC) counts for B cells, cDCs, mature stage T cells, monocytes, myeloid cells, TBNK (T cells, B cells, and natural killer cells), and Tregs, as well as the logistic parameter (MP) for cDCs and TBNK.

Results: The inverse variance weighted (IVW) analysis indicated that Myeloid DCs (p = 0.004), HVEM expression on CD45RA- CD4+ T cells (p = 0.007), CD62L- CD86+ Myeloid DCs (p = 0.015), and HLA DR expression on monocytes (p = 0.019) were associated with a reduced risk of PD. CD14+ CD16+ monocytes (p = 0.005), HLA DR+ NK cells within CD3- lymphocytes (p = 0.023), and CD28 expression on activated & secreting Tregs (p = 0.032) were associated with an increased risk of PD.

Conclusion: This study establishes a causal link between immune cell phenotype and the pathogenesis of PD, identifying several specific immune cell characteristics associated with PD. This could inspire researchers to delve into the pathogenesis of PD at the cellular subtype level, and aid in the identification of potential pharmacological protein targets for PD.

Keywords: Mendelian randomization; Parkinson's disease; causal relationship; immune cells; single nucleotide polymorphisms.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was financially supported in part by research grants from Natural Science Foundation of Fujian Province, China (2023J02024) and Medical innovation project of Fujian Province (2022CXA047).