胃食管反流病与支气管哮喘因果关系的孟德尔随机化研究  

Mendelian randomization study on causal relationship betweengastroesophageal reflux disease and bronchial asthma

作　　者：刘莲莲 王成祥 LIU Lianlian;WANG Chengxiang(Department of Respiratory Medicine,Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学第三附属医院呼吸科,北京100029

出　　处：《重庆医学》2024年第22期3361-3366,共6页Chongqing Medical Journal

基　　金：国家自然科学基金项目(82074389);首都卫生发展科研专项项目(2022-2-7034)。

摘　　要：目的基于孟德尔随机化(MR)探讨胃食管反流病(GERD)与不同支气管哮喘(简称哮喘)表型之间的因果关系。方法通过全基因组关联研究(GWAS)汇总数据集,其中GERD包含602604例患者,未指定哮喘包含156078例患者,肥胖相关性哮喘139591例患者,儿童哮喘138474例患者,过敏性哮喘140308例患者,嗜酸性粒细胞性哮喘136633例患者。采用逆方差加权法作为MR分析的主要方法,加权中位数法、简单模型、加权模型和MR-Egger进行补充,并进行敏感性分析评估结果的稳定性。结果MR分析显示,未指定哮喘(OR=1.61,95%CI:1.45~1.77,P<0.01)、肥胖相关性哮喘(OR=2.40,95%CI:1.98~2.90,P<0.01)、儿童哮喘(OR=1.56,95%CI:1.25~1.94,P<0.01)、过敏性哮喘(OR=1.47,95%CI:1.25~1.74,P<0.01)与GERD呈正向因果效应,嗜酸性粒细胞性哮喘与GERD无因果关系(OR=1.31,95%CI:0.95~1.81,P=0.10)。敏感性分析显示,结果不存在水平多效性和异质性。结论GERD会导致未指定哮喘、肥胖相关性哮喘、儿童哮喘、过敏性哮喘的患病风险升高,而对嗜酸性粒细胞性哮喘的效应不明显。Objective To investigate the causal relationship between gastroesophageal reflux disease(GERD)and different phenotypes of asthma based on Mendelian randomization(MR).Methods The dataset was pooled by genome-wide association studies(GWAS),in which the GERD data contained 602604 cases,the unspecified asthma data contained 156078 cases,139591 cases of obesity-associated asthma,138474 cases of pediatric asthma,140308 cases of allergic asthma and 136633 cases of eosinophilic asthma.The inverse variance weighting method was used as the main method of MR analysis,and the weighted median method,simple model,weighted models and MR-Egger conducted the supplement,and the sensitivity analysis was carried out to assess the stability of the results.Results The MR analysis showed that unspecified asthma(OR=1.61,95%CI:1.45-1.77,P<0.01),obesity-related asthma(OR=2.40,95%CI:1.98-2.90,P<0.01),Childhood asthma(OR=1.56,95%CI:1.25-1.94,P<0.01)and allergic asthma(OR=1.47,95%CI:1.25-1.74,P<0.01)present the forward cause effect,but eosinophilic asthma had no causal relation with GERD(OR=1.31,95%CI:0.95-1.81,P=0.10).The sensitivity analysis showed that the horizontal pleiotropy and heterogeneity in the results did not exist.Conclusion GERD could lead to an increased risk of unspecified asthma asthma,obesity-associated asthma,pediatric asthma and allergic asthma,while the effect on eosinophilic asthma is not significant.

关 键 词：胃食管反流病 哮喘 肥胖相关性哮喘 儿童哮喘 过敏性哮喘 嗜酸性粒细胞性哮喘 孟德尔随机化分析 

分 类 号：R562[医药卫生—呼吸系统]