抑郁症与非酒精性脂肪性肝病因果关系的双向孟德尔随机化研究

Bidirectional Mendelian randomization study on causal relationship between depression and non⁃alcoholic fatty liver disease

目的 采用两样本孟德尔随机化方法(Mendelian randomization,MR)研究抑郁症(major depression disease,MDD)与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的因果关系。方法 使用公开的全基因组关联研究(GenomeWide Association Study,GWAS)的汇总数据进行分析,所采用的GWAS汇总数据均来源于欧洲人群。采用逆方差加权法(inverse variance weighted,IVW)、MR-Egger回归法和加权中位数法进行双向两样本MR分析,评估抑郁症与非酒精性脂肪性肝病的因果关系。采用敏感性分析对结果的稳定性和可靠性进行评估。结果 正向MR分析结果显示,抑郁症对非酒精性脂肪性肝病风险的增加存在因果关系(IVW:OR=1.307,95%CI 1.051~1.626,P=0.016)。敏感性分析结果显示,不存在水平多效性和异质性,且留一法显示剔除任一单核苷酸多态性位点(single-nucleotide polymorphisms,SNP)均不影响总体效应估计值。反向MR结果显示,非酒精性脂肪性肝病对抑郁症发生风险不存在因果关联(P>0.05)。结论 孟德尔随机化结果显示抑郁症会增加非酒精性脂肪性肝病发病风险。

Objective To investigate the causal relationship between major depression disease(MDD)and non-alcoholic fatty liver disease(NAFLD)by two-sample Mendelian randomization(MR)methods.Methods The summary data of the publicly available Genome-Wide Association Study(GWAS)were analyzed.The GWAS summary data were all from the European population.The inverse variance weighted(IVW)method,MR-Egger regression method and weighted median method were used for bidirectional two-sample MR analysis to evaluate the causal relationship between MDD and NAFLD.Sensitivity analysis was used to evaluate the stability and the reliability of the results.Results The results of positive MR analysis showed a causal relationship between MDD and the risk of NAFLD(IVW:OR=1.307,95%CI 1.051-1.626,P=0.016).Sensitivity analysis results showed no horizontal pleiotropy or heterogenei-ty,and the leave-one-out method results showed that eliminating any single SNP did not affect the overall effect estimate.The re-sults of reverse MR analysis showed no causal relationship between NAFLD and the risk of MDD(P>0.05).Conclusion Mendelian ran-domization results suggest that MDD can increase the risk of NAFLD.