The causal relationship between asthma and chronic obstructive pulmonary disease based on a two-sample Mendelian randomization analysis

Li Yalan; Zhang Wei; Sun Shiqi; Jiang Linhong; Chen Feng

doi:10.13406/j.cnki.cyxb.003564

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The causal relationship between asthma and chronic obstructive pulmonary disease based on a two-sample Mendelian randomization analysis

Bioinformatics | 更新时间：2025-10-21

- The causal relationship between asthma and chronic obstructive pulmonary disease based on a two-sample Mendelian randomization analysis
- Journal of Chongqing Medical University Vol. 49, Issue 8, Pages: 1012-1017(2024)
- 作者机构：
  
  1.上海中医药大学曙光临床医学院,上海 201203
  2.上海中医药大学附属曙光医院肺病科,上海 201203
  3.上海中医药大学康复医学院,上海 201203
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003564
  CLC： R563
- Received：01 January 2024，
  
  Revised：2024-03-14，
  
  Accepted：01 April 2024，
  
  Published：28 August 2024
- 稿件说明：
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李雅兰,张炜,孙仕奇,等.两样本孟德尔随机化分析哮喘与慢性阻塞性肺疾病的因果关系[J].重庆医科大学学报,2024,49(8):1012-1017.

Li Yalan,Zhang Wei,Sun Shiqi,et al.The causal relationship between asthma and chronic obstructive pulmonary disease based on a two-sample Mendelian randomization analysis[J].Journal of Chongqing Medical University,2024,49(8):1012-1017.
李雅兰,张炜,孙仕奇,等.两样本孟德尔随机化分析哮喘与慢性阻塞性肺疾病的因果关系[J].重庆医科大学学报,2024,49(8):1012-1017. DOI： 10.13406/j.cnki.cyxb.003564.

Li Yalan,Zhang Wei,Sun Shiqi,et al.The causal relationship between asthma and chronic obstructive pulmonary disease based on a two-sample Mendelian randomization analysis[J].Journal of Chongqing Medical University,2024,49(8):1012-1017. DOI： 10.13406/j.cnki.cyxb.003564.

摘要

目的

采用两样本孟德尔随机化（mendelian randomization，MR）方法探究哮喘和慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）间是否存在因果关系。

方法

从全基因组关联研究（genome-wide association studies，GWAS）汇总数据中筛选出与哮喘强相关的单核苷酸多态性（single nucleotide polymorphism，SNP）作为工具变量，采用逆方差加权法（inverse variance weighted，IVW）作为主要分析方法，MR-Egger法、加权中位数法、简单模型和加权模型作为辅助分析方法，以评价哮喘和COPD发病风险之间的因果关系，同时采用孟德尔随机多态性残差和离群值（mendelian randomization pleiotropy residual sum and outlier，MR-PRESSO）检验检测是否存在离群的SNP，MR-Egger截距测试、Cochran Q检验评估工具变量的水平多效性和异质性。

结果

共纳入61个SNP，IVW结果显示，哮喘是COPD的危险因素（

=1.146，95%CI=1.023-1.283，

=0.020；

=1.153，95%CI=1.003~1.326，

=0.045），其余4种辅助分析方法的结果与IVW方法显示的结果一致，MR-PRESSO检验、Cochran Q检验、MR-Egger截距测试以及留一法的结果均显示了结果的稳定性。

结论

哮喘是COPD的危险因素。

Abstract

Objective

To investigate whether there is a causal relationship between asthma and chronic obstructive pulmonary disease（COPD） using the two-sample Mendelian randomization（MR） approach.

Methods

Single nucleotide polymorphisms（SNPs） strongly associated with asthma were obtained as instrumental variables（IVs） from the pooled data of genome-wide association studies，and the inverse variance weighted（IVW） method was used as the main analytical method，assisted by the methods of MR-Egger，weighted median，simple model，and weighted model，to evaluate the causal relationship between asthma and the risk of COPD. At the same time，the MR-PRESSO test was used to detect whether there was an outlier SNP，and the MR-Egger intercept test and the Cochran Q test were used to evaluate the horizontal pleiotropy and heterogeneity of IVs.

Results

A total of 61 SNPs were included，and IVW results showed that asthma is a risk factor for COPD.（odds ratio［

］=1.146，95%CI=1.023-1.283，

=0.020；

=1.153，95% CI=1.003-1.326，

=0.045），and the results of the other four auxiliary analysis methods wer

e consistent with the results of IVW. The results of the MR-PRESSO test，the Cochran Q test，the MR-Egger intercept test，and the leave-one-out method all showed the stability of the above results.

Conclusion

Asthma may increase the risk of COPD.

关键词

Keywords

references

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