Comprehensive two-sample mendelian randomization analysis of serum metabolites and trigeminal neural-gia
Objective To comprehensively investigate and study the possible causal relationship between serum metabolites and trigeminal neuralgia,providing new ideas for subsequent treatment and management of patients with trigeminal neuralgia.Methods Summarized data of Genome-Wide Association Studies(GWASs)of serum metabolites and trigeminal neuralgia were obtained from the Genome-Wide Association Study(GWAS)Catalog and the Finnish database FINNGEN R10.With 486 serum metabolites as exposure factors and trigeminal neuralgia as the outcome,a two-sample Mende-lian randomization(MR)study was conducted to explore the causal effect of serum metabolites on tri-geminal neuralgia.The inverse variance weighted(1VW)method was used as the causal estimation method,accompanied by a series of sensitivity analyses to assess the robustness of the results.In addi-tion,MetaboAnalyst based on network analysis was used for metabolic pathway analysis.P<0.05 was considered as statistically significant.Results After correcting for false discovery rate(FDR),the MR analysis results showed significant causal relationships with 7 metabolites,namely phosphate(OR=0.00,95%CI:0.00-0.05),benzoic acid(OR=4.34,95%CI:1.86-10.11),1-stearoyl-glycerophos-phoinositol(OR=3.18,95%CI:1.93-5.24),palmitoylcarnitine(OR=0.15,95%CI:0.05-0.44),py-roglutamylglycine(OR=2.13,95%CI:1.39-3.27),10-heptadecenoate(OR=4.33,95%CI:2.11-8.88),and 4-vinylphenol sulfate(OR=2.15,95%CI:1.46-3.15).However,after further sensitivity analysis,no specific metabolite passed all sensitivity tests,and heterogeneity was found in Cochran's Q test for all metabolites.Seven metabolites passed two sensitivity tests,namely MR-Egger intercept test and leave-one-out analysis,and were considered robust.In addition,metabolic pathway enrich-ment analysis of the seven metabolites identified 44 metabolic pathways related to the phenotype of tri-geminal neuralgia,of which three had P<0.01:thiamine metabolism,lactose degradation,and tria-cylglycerol biosynthesis.Conclusion Seven metabolites and their related metabolic pathways may have a causal association with trigeminal neuralgia,which will contribute to the diagnosis and treatment of trigeminal neuralgia.
Trigeminal neuralgiaSerum metabolitesMendelian randomizationGenome-wide association studies