双样本孟德尔随机化研究探讨肠道微生物与肝癌的关系

Relationship between gut microbiota and hepatocellular carcinoma through two-sample Mendelian randomization study

目的通过双样本孟德尔随机化方法探讨221种肠道微生物与肝癌是否存在关联,为肝癌防治提供思路。方法使用IEU OpenGWAS数据库的肝癌数据(n=197611)作为结局数据,从一项大规模多种族基因组关联研究的元分析中获取肠道微生物数据(n=18340)作为暴露数据,主要采用逆方差加权法进行分析,根据效应指标优势比(OR)和95%CI评估结果,同时使用留一法和异质性检验以及MR-PRESSO方法进行质量控制。结果颤螺菌属(Oscillibacter)丰度的提升,可以增加肝癌的患病概率(OR=1.411,95%CI:1.049~1.899,P=0.025)。留一法分析结果表明,该研究的结果稳定,并且未发现对结果产生强烈影响的工具变量。结果显示肠道微生物与肝癌之间存在正向的因果关系,并且可以消除异质性和水平基因多效性对因果效应估计所产生的影响。结论颤螺菌属丰度的提升,可以增加肝癌的患病概率。

Objective To investigate the potential association between 221 types of gut microbiota and hepatocellular carcinoma(HCC)using a two-sample Mendelian randomization approach,providing insights for the prevention and treatment of HCC.Methods The HCC data(n=197611)from the IEU OpenGWAS database was used as outcome data,while gut microbiota data(n=18340)obtained from a meta-analysis of a large-scale multi-ethnic genome-wide association study was used as exposure data.The analysis primarily employed the inverse variance weighting method,assessing the results based on the odds ratio(OR)and 95%confidence interval(CI).Quality control was conducted using leave-one-out analysis,heterogeneity tests,and the MR-PRESSO method.Results An increased abundance of the genus Oscillibacter was associated with a higher probability of developing HCC(OR=1.411,95%CI:1.049-1.899,P=0.025).Leave-one-out analysis indicated that the study results were stable and no instrumental variables had a strong impact on the results.This showed a positive causal relationship between gut microbiota and HCC,which could eliminate the effects of heterogeneity and horizontal gene pleiotropy on causal effect estimation.Conclusion An increased abundance of the genus Oscillibacter may raise the probability of developing HCC.