脓毒症与心律失常因果关联的两样本孟德尔随机化研究

Causal relationship between sepsis and arrhythmia:a two-sample Mendelian randomization

目的探索脓毒症与心律失常之间的因果关联。方法以公开发表的全基因组关联性分析作为数据源,筛选出与脓毒症显著相关的单核苷酸多态性作为工具变量,采用两样本孟德尔随机化法中的逆方差加权法、加权中位数法、孟德尔随机化-Egger分析法、简单模式法和加权模式法评估脓毒症与心律失常之间的因果关联。通过异质性分析、多效性分析及敏感性分析评估结果的可靠性和稳定性。结果筛选出52个强工具变量进行两样本孟德尔随机化分析,仅逆方差加权法分析结果显示差异有统计学意义(OR=1.002,95%CI 1.001~1.003,P=0.002);其余四种分析方法结果差异无统计学意义(均P>0.05),但其效应值β与逆方差加权法的效应值β方向相同;异质性分析、多效性分析及敏感性分析结果均显示P>0.05。结论脓毒症与心律失常之间存在因果关联,即脓毒症会增加心律失常发生的风险。

Objective To explore the causal relationship between sepsis and arrhythmia.Methods Using the published genome-wide association analysis as the data source,single nucleotide polymorphisms significantly associated with sepsis were screened as instrumental variables.The method of two-sample Mendelian randomization,which included inverse variance weighted method,weighted median method,MR Egger analysis method,simple model method and weighted model method,were used to evaluate the causal relationship between sepsis and arrhythmia.At the same time,heterogeneity analysis,pleiotropy analysis and sensitivity analysis were used to evaluate the reliability and stability of the results.Results 52 strong instrumental variables were screened out for the analysis of two-sample Mendelian randomization,only the inverse variance weighting analysis showed statistical difference(OR=1.002,95%CI 1.001-1.003,P=0.002),and the results of the other four analysis methods had no statistical difference(P>0.05),but the effect valueβwas in the same direction as that of inverse variance weighting method;The results of heterogeneity analysis,pleiotropy analysis,and sensitivity analysis all showed P>0.05.Conclusions There is a causal relationship between sepsis and arrhythmia,and sepsis increases the risk of arrhythmias.