【摘要】 目的 旨在利用双向两样本孟德尔随机化方法，评估EB病毒感染的VCAp18抗体水平和EBNA-1抗体水平与幽门螺杆菌感染的VacA抗体水平和OMP抗体水平之间的潜在因果关系。方法 利用公开的GWAS汇总数据，以显著相关的SNP为工具变量。EBV抗体(VCAp18、EBNA-1)和HP抗体(VacA、OMP)数据样本量分别为8518/7972和2640/1571。采用逆方差加权(IVW)为主要分析方法，辅以加权中位数、MR-Egger,并进行多效性、异质性与敏感性检验。结果 IVW分析显示，遗传预测的EBV抗体水平升高与HP抗体水平降低存在负向因果关联。具体而言，EBNA-1抗体水平与OMP抗体水平风险降低相关(OR=0.854,95%CI:0.745-0.979),VCAp18抗体水平与VacA抗体水平风险亦降低相关(OR=0.796,95%CI:0.652-0.972)。敏感性分析结果稳健，未发现明显的水平多效性或异质性。反向MR分析未发现显著关联。结论 首次通过遗传学证据提示，EBV抗体水平对HP抗体水平可能存在抑制作用，为理解两种病原体的交互作用提供了新视角。更多还原

【Abstract】 Objective This study aims to utilize bidirectional two-sample Mendelian randomization(MR) to evaluate the potential causal relationship between Epstein-Barr virus(EBV) infection, as measured by the VCAp18 and EBNA-1 antibody levels, and Helicobacter pylori(HP) infection, as indicated by VacA and OMP antibody levels.Methods Publicly available GWAS summary data were used, with significant SNPs serving as instrumental variables.The sample sizes for the EBV antibodies(VCAp18,EBNA-1) and HP antibodies(VacA,OMP) were 8518/7972 and 2640/1571,respectively.The primary analysis employed inverse variance weighting(IVW),supplemented by weighted median, MR-Egger regression, and tests for pleiotropy, heterogeneity, and sensitivity.Results IVW analysis revealed a negative causal relationship between genetically predicted higher EBV antibody levels and lower HP antibody levels.Specifically, higher EBNA-1 antibody levels were associated with a reduced risk of OMP antibody levels(OR= 0.854,95% CI:0.745-0.979),and higher VCAp18 antibody levels were associated with a decreased risk of VacA antibody levels(OR= 0.796,95% CI:0.652-0.972).Sensitivity analyses demonstrated robustness, with no significant evidence of horizontal pleiotropy or heterogeneity.No significant association was found in reverse MR analysis.Conclusion This study provides, for the first time, genetic evidence suggesting that EBV antibody levels may exert an inhibitory effect on HP antibody levels, offering new insights into the interaction between these two pathogens.更多还原