Objective: To investigate the causal relationship between blood metabolites and liver cirrhosis using Mendelian randomization (MR) analysis. Methods: Single nucleotide polymorphisms (SNPs) significantly associated with blood metabolite levels were selected as instrumental variables. Two-sample MR analysis was performed using genome-wide association study (GWAS) data to assess the causal effects of metabolites on cirrhosis risk. Methods including inverse variance weighting (IVW), weighted median, and MR-Egger regression were employed. Sensitivity analyses were conducted using MR-pleiotropy residual sum and outlier (MR-PRESSO) and "leave-one-out" methods. Results: IVW analysis showed that the glucose-to-sorbitol ratio was negatively associated with the risk of cirrhosis (OR=0.650, 95% CI: 0.523-0.809, P=0.001). Sensitivity analyses did not indicate horizontal pleiotropy or heterogeneity. Conclusion: The glucose-to-sorbitol ratio may be negatively causally associated with the occurrence of cirrhosis, suggesting that elevated sorbitol levels may be a risk factor for cirrhosis.
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