Genetic determinants of cerebrospinal fluid metabolites and risk of Guillain-Barré syndrome: A bidirectional two-sample Mendelian randomization study

This study aims to investigate the potential causal relationship between cerebrospinal fluid (CSF) metabolites and Guillain-Barré syndrome (GBS) using a bidirectional two-sample Mendelian randomization (MR) approach. Publicly available summary data from genome-wide association studies (GWAS) were utilized for comprehensive analysis. The CSF metabolite GWAS summary data were extracted from a GWAS conducted by Panyard et al encompassing 338 CSF metabolites in European participants (n = 291). GWAS summary statistics for GBS were obtained from the FinnGen consortium (n = 215,931) comprising European populations. The primary method for MR analysis was the inverse variance weighted method. Various sensitivity analyses were conducted to assess the heterogeneity and pleiotropy of the findings. In the forward MR analysis, we identified a causal relationship between 15 CSF metabolites, including ribitol levels (odds ratio = 3.833, 95% confidence interval: 1.949-7.540, P = 9.87E-05), and the risk of developing GBS. In the reverse MR analysis, we found a causal relationship between GBS and 21 CSF metabolites, including gamma-glutamylphenylalanine levels (odds ratio = 0.934, 95% confidence interval: 0.904-0.966, P = 7.10E-05). No evidence of heterogeneity or horizontal pleiotropy was found in the MR analysis. Our findings suggest that the identified CSF metabolites and metabolic pathways can serve as valuable biomarkers for clinical screening and prevention of GBS. They may also be considered as candidate molecules for future research into the underlying mechanisms and for selecting drug targets.