Pathogen Antibodies and Parkinson's Disease: A Two-sample Mendelian Randomization Study.

Area of Science:

• Neuroimmunology
• Infectious Disease Epidemiology
• Genetic Epidemiology

Background:

• Parkinson's disease (PD) pathogenesis may involve infection-induced immune responses.
• Establishing a causal link between pathogen exposure and PD is challenging using observational data.
• Mendelian randomization (MR) offers a robust approach to investigate causality.

Purpose of the Study:

• To explore the potential causal relationship between pathogen-derived antibodies and Parkinson's disease risk.
• To utilize a two-sample Mendelian randomization (MR) analysis for robust genetic evidence.
• To identify specific infectious agents or immune responses associated with PD etiology.

Main Methods:

• A two-sample Mendelian randomization (MR) analysis was performed.
• Genetic variants associated with 46 pathogen antibodies were analyzed using genome-wide association study (GWAS) data.
• Inverse variance weighted (IVW) method was the primary analysis, with MR-Egger and weighted median for robustness checks.

Main Results:

• Elevated human herpesvirus 6 (HHV-6) p101k antibody levels were significantly associated with increased PD risk (OR: 1.08).
• Suggestive evidence indicated potential protective associations for Helicobacter pylori GroEL and Merkel cell polyomavirus (MCPyV) VP1 antibodies.
• Sensitivity analyses were conducted to ensure the robustness of the findings.

Conclusions:

• Specific pathogen antibody responses may play a role in the etiology of Parkinson's disease.
• The association with HHV-6 antibodies suggests a potential role for virus-induced neuroinflammation in PD.
• Further research into Helicobacter pylori GroEL and MCPyV VP1 associations is warranted to confirm protective effects.