基于双向两样本孟德尔随机化的情绪波动与非酒精性脂肪性肝病因果关系分析OA

Objective:Based on Mendelian randomization(MR)study design,to reveal the potential bidirectional causal association between emotional fluctuation and non-alcoholic fatty liver disease(NAFLD)in this study.Method:Single nucleotide polymorphisms(SNPs)significantly associated with the exposure(mood swings)were selected from genome-wide association study(GWAS)data as instrumental variables(Ⅳs),extracted based on predefined threshold parameters.The inverse variance weighted(IVW)method was used as the primary analysis to estimate causal effects between exposure and outcome,with supplementary analyses including the weighted median method,MR Egger regression,weighted mode method,and simple model method to fully validate result robustness and reliability,and to evaluate the association between emotional fluctuation-related phenotypes and NAFLD onset.Sensitivity analysis was conducted,including pleiotropy tests,heterogeneity tests and leave-one-out analysis to assess the robustness of the results.Result:A total of 56 SNPs associated with mood swings were identified.IVW analysis revealed a causal relationship between mood swings and non-alcoholic fatty liver disease[OR=1.9528,95%CI(1.021 0,3.735 1),P=0.043 1].Cochran's Q test results(Q=48.790 1,df=55,P=0.709 4)indicated no heterogeneity among the SNPs.MR-PRESSO analysis detected no outliers(P=0.924 1).Leave-one-out analysis demonstrated that no single SNP significantly influenced the causal relationship.Conclusion:Genetically predicted mood swings show a positive causal association with the risk of non-alcoholic fatty liver disease(NAFLD).This study provides genetic evidence supporting the traditional Chinese medicine theory that"emotional distress impairs the liver",but further research is needed for validation.