The Mediating Factor of Immune Cell in the Causal Relationship Between Cardiovascular Disease-Related Plasma Proteins and Parkinson's Disease: A Network Mendelian Randomization Analysis
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Ruotong Yao1,2, Siyao Chen1,2, Yangguang Lu1,2
1Department of Neurology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, 150 Ximen Road Linhai City, Taizhou, Zhejiang, China, wmu.edu.cn.
Insights
Cardiovascular disease proteins show genetic links to Parkinson's disease (PD) risk. Immune cell phenotypes significantly mediate this association, offering new research avenues.
Area of Science:
- Genetics
- Immunology
- Neurology
- Cardiovascular Science
Background:
- Cardiovascular diseases (CVDs) and associated plasma proteins are linked to immunity and Parkinson's disease (PD).
- The precise role of CVD-related proteins in PD risk is not fully understood.
- Investigating these links is crucial for understanding PD pathogenesis.
Purpose of the Study:
- To determine the potential causal relationship between CVD-related plasma proteins and PD risk.
- To explore the mediating role of immune cell phenotypes in this association.
- To provide insights for future research and clinical applications.
Main Methods:
- Mendelian randomization (MR) analysis using publicly available genetic data.
- Inverse variance weighting method applied to 83 CVD-related proteins and PD.
- Bioinformatics analyses including protein-protein interaction networks and pathway enrichment.
- Mediator MR design to assess 731 immune cell phenotypes.
Main Results:
- Fas cell surface death receptors and nerve growth factor linked to reduced PD risk (p=0.015, p=0.026).
- Thrombomodulin associated with increased PD risk (p=0.028).
- Four immune phenotypes significantly mediate the relationship between CVD proteins and PD pathogenesis.
- Sensitivity analyses confirmed the robustness of the findings.
Conclusions:
- A significant genetic association exists between CVD-related plasma proteins and PD.
- Immune cell phenotypes play a crucial mediating role in PD development.
- Findings offer valuable insights for future research and clinical strategies targeting PD.
Background:
Cardiovascular diseases (CVDs) and their associated plasma proteins exhibit significant correlations with immunity and Parkinson's disease (PD). However, the specific contributions to the risk of developing PD remain unclear. This study aims to investigate the potential causal relationship between CVD-related plasma proteins and the risk of PD and explore the significant mediating role of immune cell phenotypes.
Methods:
Using publicly available genetic data, we conducted Mendelian randomization (MR) analysis using the inverse variance weighting method to explore the causal relationship between 83 CVD-related plasma proteins and PD. Various MR analysis models were employed for sensitivity analysis. Concurrently, we utilized bioinformatics methods such as protein-protein interaction networks and pathway enrichment analysis to investigate the potential associations between CVD-related plasma proteins and PD-related genes. Finally, we employed a mediator MR design to identify the mediating effects of 731 immune cell phenotypes in the onset of PD.
Results:
Elevated levels of Fas cell surface death receptors (p = 0.015) and nerve growth factor (p = 0.026) are associated with a reduced risk of PD, while increased levels of thrombomodulin (p = 0.028) are a risk factor for PD. Four immune phenotypes play a significant mediating role in the association between CVD-related proteins and the pathogenesis of PD. Sensitivity analysis indicates that the results are robust.
Conclusions:
Our study elucidates the close genetic association between CVD-related plasma proteins and PD and identifies the significant mediating role of immune cells, thereby providing valuable insights for future research and clinical applications.
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