Mendelian randomization-based exploration of bidirectional causal relationship between gastroesophageal reflux disease and interstitial lung disease

Zhang Jing; Li Fang; Lai Fang; Zhou Gengbiao

doi:10.13406/j.cnki.cyxb.003398

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Mendelian randomization-based exploration of bidirectional causal relationship between gastroesophageal reflux disease and interstitial lung disease

Mendelianrandomization | 更新时间：2025-10-22

- Mendelian randomization-based exploration of bidirectional causal relationship between gastroesophageal reflux disease and interstitial lung disease
- Journal of Chongqing Medical University Vol. 48, Issue 12, Pages: 1456-1461(2023)
- 作者机构：
  
  1.广州中医药大学第二临床医学院，广州 510405
  2.广州中医药大学第二附属医院重症医学科，广州 510145
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003398
  CLC： R571;R563
- Received：10 October 2023，
  
  Revised：2023-11-09，
  
  Accepted：30 November 2023，
  
  Published：28 December 2023
- 稿件说明：
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张静,李芳,赖芳,等.基于孟德尔随机化探讨胃食管反流与间质性肺病的双向因果关系[J].重庆医科大学学报,2023,48(12):1456-1461.

Zhang Jing,Li Fang,Lai Fang,et al.Mendelian randomization-based exploration of bidirectional causal relationship between gastroesophageal reflux disease and interstitial lung disease[J].Journal of Chongqing Medical University,2023,48(12):1456-1461.
张静,李芳,赖芳,等.基于孟德尔随机化探讨胃食管反流与间质性肺病的双向因果关系[J].重庆医科大学学报,2023,48(12):1456-1461. DOI： 10.13406/j.cnki.cyxb.003398.

Zhang Jing,Li Fang,Lai Fang,et al.Mendelian randomization-based exploration of bidirectional causal relationship between gastroesophageal reflux disease and interstitial lung disease[J].Journal of Chongqing Medical University,2023,48(12):1456-1461. DOI： 10.13406/j.cnki.cyxb.003398.

摘要

目的

临床观察及流行病学调查发现胃食管反流病（gastroesophageal reflux disease，GERD）与间质性肺疾病（interstitial lung disease，ILD）具有相关性，本文章旨在通过孟德尔随机化分析（Mendelian randomization，MR）方法，研究GERD与ILD是否相互存在因果关联，以及这些关联的方向性。

方法

从全基因组关联研究（genome-wide association studies，GWAS）汇总数据中选择符合条件的单核苷酸多态性（single nucleotide polymorphisms，SNPs）作为工具变量（instrumental variables，IVs）进行分析，分别采用逆方差加权法（inverse-variance weighted，IVW）、MR-Egger回归分析、加权中位数法（weighted median estimator，WME）等进行两样本孟德尔随机化分析，其中IVW用于主要分析；在进行敏感性分析时，采用MR-PRESSO检验和MR-Egger回归分析以检测和纠正水平多效性；采用留一法、Cochran’s Q检验、漏斗图以评估MR结果的稳定性和可靠性，以

值评价GERD与ILD的因果关系。

结果

IVW结果

显示GERD可增加患ILD的风险，GERD对数变换后每增加一个标准差，会导致ILD的风险增加22%（

=1.22，95%CI=1.11~1.33，

=3.52e-05）。反之，ILD也可增加患GERD的风险。

结论

GERD与ILD具有双向因果关系。

Abstract

Objective

Clinical observations and epidemiological investigations have found an association of gastroesophageal reflux disease（GERD） with interstitial lung disease（ILD）. We aimed to investigate whether GERD and ILD are causally associated with each other and the direction of the association through Mendelian randomization（MR） analysis.

Methods

Eligible single nucleotide poly⁃morphisms（SNPs）were selected as instrumental variables（IVs） from the pooled data of genome-wide association studies（GWAS）.Two-sample Mendelian randomization analyses were performed using the inverse-variance weighted method（IVW），the MR-Egger regression method，and the weighted median estimator（WME）. The IVW method was used as the main causal analysis. The MR-PRESSO test and MR-Egger regression method were used in sensitivity analysis to detect and correct for horizontal pleiotropy. The leave-one-out method，Cochran’s Q test，and funnel plot were used to assess the stability and reliability of MR results. The odds ratio（

） was used to evaluate the causality between GERD and ILD.

Results

The IVW results showed that GERD increased the risk of ILD，and each standard deviation increase in log-transformed GERD resulted in a 22% increase in the risk of ILD（

=1.22，95%CI=1.11-1.33，

=3.52e-05）. Conversely，ILD also increased the risk of GERD.

Conclusion

GERD and ILD have a bidirectional causal relationship.

关键词

Keywords

references

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