基于两样本孟德尔随机化分析哮喘与胃食管反流病因果关系的研究

Causal relationship between asthma and gastroesophageal reflux disease based on twosample Mendelian randomization

目的采用两样本孟德尔随机化(Mendelian randomization,MR)研究方法评估哮喘与胃食管反流病(gastroesophageal reflux disease,GERD)发生风险之间的潜在因果关系。方法利用大样本全基因关联研究汇总数据,选择与哮喘密切相关的遗传位点[单核苷酸多态性(single nucleotide polymorphism,SNP)]作为工具变量,分别采用逆方差加权法、加权中位数法和MR-Egger法进行MR分析。同时采用MR-Egger检测水平多效性,留一法进行敏感性分析保证结果稳健性。结果共纳入77个SNP作为评估哮喘与GERD因果关联的工具变量。逆方差加权法分析结果显示哮喘与GERD呈正相关[比值比(odds ratio,OR)=1.044,95%置信区间(confidence interval,CI)(1.006,1.083),P=0.024],加权中位数结果显示了相似的因果关系[OR=1.075,95%CI(1.021,1.133),P=0.006]。MR-Egger回归结果显示,哮喘与GERD呈正相关,但无统计学意义[OR=1.080,95%CI(0.983,1.187),P=0.115]。异质性检验结果显示,哮喘与GERD的因果关系不存在异质性(P>0.05)。水平多效性检验结果显示SNP不存在水平多效性(P>0.05)。留一法检验结果显示,未检测到对结果影响大的SNP。结论哮喘与GERD存在正向因果关系。

Objective To evaluate the potential causal relationship between asthma and the risk of gastroesophageal reflux disease(GERD)using a two-sample Mendelian randomization study.Methods A large sample of genome-wide association study was used to summarize the data,and the genetic loci[single nucleotide polymorphisms(SNPs)]closely related to asthma were selected as instrumental variables,and Mendelian randomization analysis was conducted by inverse variance weighting,weighted median and MR-Egger method,respectively.At the same time,the multi-effect of MR-Egger was detected and the sensitivity analysis was carried out by Leave-one-out method to ensure the robustness of the results.Results A total of 77 SNPs closely related to asthma were selected as instrumental variables.The results of inverse variance weighted analysis showed a significant positive correlation between asthma and the occurrence of gastroesophageal reflux disease[odds ratio(OR)=1.044,95%confidence interval(CI)(1.006,1.083),P=0.024].Weighted median results showed similar causality[OR=1.075,95%CI(1.021,1.133),P=0.006].The MR-Egger regression results showed that there was a positive correlation between asthma and GERD,but there was no statistical significance[OR=1.080,95%CI(0.983,1.187),P=0.115].The heterogeneity test results showed that there was no heterogeneity in the causal relationship between asthma and GERD(P>0.05).The results of the horizontal pleiotropy test showed that there was no horizontal pleiotropy in SNPs(P>0.05).The results of the retention test showed that no SNPs with significant impact on the results were detected.Conclusion There is a positive causal relationship between asthma and GERD.