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

李雅兰; 张炜; 孙仕奇; 姜林鸿; 陈凤

doi:10.13406/j.cnki.cyxb.003564

重庆医科大学学报 ›› 2024, Vol. 49 ›› Issue (08) : 1012 -1017. DOI: 10.13406/j.cnki.cyxb.003564

生物信息学

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

李雅兰 ¹ ,
张炜 ² ,
孙仕奇 ² ,
姜林鸿 ³ ,
陈凤 ¹

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

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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（OR=1.146，95%CI=1.023-1.283，P=0.020； OR=1.153，95%CI=1.003~1.326，P=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［OR］=1.146，95%CI=1.023-1.283，P=0.020； OR=1.153，95% CI=1.003-1.326，P=0.045），and the results of the other four auxiliary analysis methods were 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.