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基于孟德尔随机化分析胃食管反流病与慢性阻塞性肺疾病的因果关系研究

Causal relationship between gastroesophageal reflux disease and chronic obstructive pulmonary disease based on Mendelian randomization analysis

    摘要
  • 摘要:
    目的  基于双向两样本孟德尔随机化(MR)方法分析胃食管反流病(GERD)与慢性阻塞性肺疾病(COPD)的因果关系。
    方法  从全基因组关联研究(GWAS)中获取GERD与COPD的遗传变异信息, 并以此作为工具变量。采用逆方差加权法(IVW)、加权中位数法和MR-Egger回归分析法进行MR分析，并通过敏感性分析验证结果的稳健性。
    结果  遗传预测的GERD与COPD发生风险具有显著正相关性，而COPD与GERD发生风险无统计学关联。正向IVW结果显示比值比(OR)=1.305 7, 95%置信区间(95%CI)为1.114 4~1.529 8, P=0.000 9; 逆向IVW结果显示OR=0.982 3, 95%CI为0.917 4~1.051 9, P=0.610 4。敏感性分析未发现任何潜在偏倚。
    结论  MR分析显示GERD是COPD的一个风险因子，治疗GERD可能有助于预防或延缓COPD的进展。

     

    Abstract:
    Objective  To analyze the causal relationship between gastroesophageal reflux disease (GERD) and chronic obstructive pulmonary disease (COPD) based on the bidirectional two-sample Mendelian randomization (MR).
    Methods  Genetic variation information of GERD and COPD was obtained from Genome-Wide Association Studies (GWAS) and used as instrumental variables. Inverse variance-weighted (IVW), weighted median and MR-Egger methods were used for MR analysis, and sensitivity analysis was performed to validate the robustness of the results.
    Results  A significant positive correlation was observed between genetically predicted GERD and the incidence risk of COPD, but there was no statistical association between COPD and the incidence risk of GERD. Positive IVW result showed that the odds ratio (OR) was 1.305 7, the 95% confidence interval (95%CI) was 1.114 4 to 1.529 8, and the P value was 0.000 9; the reverse IVW result showed that the OR was 0.982 3, the 95%CI was 0.917 4 to 1.051 9, and the P value was 0.610 4. Sensitivity analysis did not find any potential bias.
    Conclusion  MR analysis shows that GERD is a risk factor for COPD, and treating GERD may help prevent or delay the progression of COPD.

     

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