Exploring the Causal Links Between 338 Cerebrospinal Fluid Metabolites and Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by motor impairments and intricate pathophysiological mechanisms. Although cerebrospinal fluid (CSF) metabolites are viewed as potential biomarkers, the primarily observational design of the majority of existing studies limits the ability to draw causal conclusions.

The purpose of this research was to explore the causal link between CSF metabolites and PD by employing two-sample Mendelian randomization (TSMR).

Data on CSF metabolites were acquired from the two longitudinal cohort studies. Information regarding PD was gathered from the International Parkinson's Disease Genomics Consortium. Instrumental variables (IVs) for 338 CSF metabolites were identified based on notable SNPs. Causal impacts were assessed using Mendelian randomization techniques including inverse variance weighted (IVW) analysis and MR-Egger regression. The analyses included sensitivity assessments to evaluate issues related to heterogeneity and pleiotropy.

Significant causal associations were found between several CSF metabolites and PD. Higher levels of glycerophosphoinositol, sphingomyelin, and oxalate were linked to increased PD risk, while elevated caffeine levels appeared protective. After FDR correction, glycerophosphoinositol, oxalate, and caffeine remained significant. Sensitivity analyses confirmed robustness with no heterogeneity or pleiotropy.

This analysis of MR reveals multiple CSF metabolites that have causal links to PD. Increased levels of glycerophosphoinositol and oxalate are associated with higher risk, whereas caffeine provide protective benefits. These metabolites may act as potential biomarkers and treatment targets for PD.