Objective:Viral hepatitis(VH)may lead to severe impairment of liver function.And the relationship between serum metabolites and VH has not been clarified.The aim of this study is to explore the potential association between serum metabolites and VH using Mendelian randomization(MR).Methods:A two-sample bidirectional MR analysis was conducted using serum metabolites data from the Genome-Wide Association Study Catalog(GWAS Catalog)and VH data from the FinnGen R 10.5 MR methods were applied:inverse variance weighting(IVW),weighted median,MR-Egger regression,weighted mode,and simple mode.The statistical power of the MR results was evaluated using power statistics.Sensitivity analyses were conducted with Cochran's Q test,MR-Egger regression,MR-PRESSO,Steiger's test,and the leave-one-out method.Separate reverse MR analyses were conducted on serum metabolites that demonstrated a causal association with VH in the forward MR analysis.Finally,a pathway enrichment analysis was performed for metabolites with significant causal associations.Results:After applying false discovery rate(FDR)correction,eight serum metabolites were identified as being associated with the risk of VH based on IVW results.Glutamine,tetradecanoate,valine,and 4-methyl-2-oxovaleric acid were identified as potential protective metabolites against VH.In contrast,inositol,cholate,pyridoxine,and γ-tocopherol were significantly associated with an increased risk of VH.The level of tetradecanoate was also significantly elevated post-VH.All findings were free from heterogeneity and pleiotropy.Furthermore,ascorbate and malonate metabolism,as well as the vitamin B6 pathway,were identified as key metabolic pathways linking these metabolites to VH.Conclusion:Serum metabolites show a significant association with VH,suggesting that monitoring and regulating these metabolites could help in the prevention,diagnosis,and treatment of VH.
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