孟德尔随机化分析探讨组织蛋白酶与酒精性肝病的因果关系OA

Objective:To investigate the causal relationship between cathepsins and alcoholic liver disease by two-sample Men-delian randomization(MR).Methods:A two-way two-sample MR was designed to assess the causal relationship between cathep-sins and alcoholic liver disease,using single nucleotide polymorphisms as instrumental variables.Aggregate genome-wide associa-tion studies(GWAS)data for 11 cathepsins and alcoholic liver disease were extracted from GWAS in public databases.In the for-ward MR analysis,each cathepsin was used as the exposure and alcoholic liver disease was used as the outcome.In reverse MR analysis,alcoholic liver disease was used as the exposure and each cathepsin was used as the outcome.Inverse variance weighted was used as the primary analysis method for both directions and other methods were used as supplementary references to assess causal effects.Heterogeneity and pleiotropy tests were also performed and the stability of the results was assessed using the reten-tion one method.Results:Genetically predicted cathepsin V was associated with a reduced risk of alcoholic liver disease(IVW:OR=0.853,95%CI=0.743‒0.980),and alcoholic liver disease was associated with an increase in cathepsin B(IVW:OR=1.054,95%CI=1.006‒1.105).Conclusion:High levels of cathepsin V may reduce the risk of alcoholic liver disease,the presence of which increases the expression of cathepsin B,and the absence of a causal association between other cathepsin and alcoholic liv-er disease studies and other reverse studies,and the results need to be validated by further laboratory studies and evidence from fu-ture studies with larger sample sizes.