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

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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

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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.

关键词

哮喘 / 慢性阻塞性肺疾病 / 孟德尔随机化 / 全基因组关联研究

Key words

asthma / chronic obstructive pulmonary disease / Mendelian randomization / genome-wide association studies

中图分类号

R563

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导出引用
李雅兰 , 张炜 , 孙仕奇 , . 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. 重庆医科大学学报. 2024, 49(08): 1012-1017 https://doi.org/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(08): 1012-1017 https://doi.org/10.13406/j.cnki.cyxb.003564

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基金

上海市市级科技重大专项资助项目(ZXS004R4-2)
上海市中医呼吸专科联盟资助项目(ZY(2021-2023)-0302)
上海中医内科临床重点实验室资助项目(20DZ2272200)

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