摘要
目的 采用两样本孟德尔随机化(mendelian randomization,MR)方法探究肥胖与肺部疾病的因果关系.方法 采用逆方差加权法(inverse variance weighted,IVW)和6种基于不同假设下的MR方法,利用全基因组关联研究(genome-wide association study,GW AS)汇总数据,评估内脏脂肪组织(visceral adipose tissue,VAT)与肺部疾病(慢性阻塞性肺病、睡眠呼吸暂停、肺癌、肺炎、肺栓塞、特发性肺纤维化、肺结核)之间的因果关系.采用留一法、Cochran's Q检验,MR-Egger回归截距项检验、MR-PRESSO检验进行敏感性分析,评估工具变量的异质性、多效性和稳定性.结果 IVW结果表明,遗传学预测的较高VAT与慢性阻塞性肺病(OR=1.56,95％CI:1.33～1.84,P＜0.001)、睡眠呼吸暂停(OR=1.76,95％CI:1.53～2.03,P＜0.001)、肺癌(OR=1.39,95％CI:1.23～1.58,P＜0.001)、肺炎(OR=1.22,95％CI:1.15～1.30,P＜0.001)的较高发生风险存在因果关联.除了 MR-Egger,其他4种MR方法结果均与主要分析结果一致.此外,有提示性证据支持较高VAT会增加肺栓塞(OR=1.18,95％CI:1.04～1.34,P=0.009)和特发性肺纤维化(OR=1.00,95％CI:1.00～1.00,P=0.011)的发生风险.结论 VAT累积可能增加慢性阻塞性肺病、睡眠呼吸暂停、肺癌、肺炎、肺栓塞和特发性肺纤维化的发生风险.
Abstract
Objective To investigate the causal relationship between obesity and lung diseases using Mendelian randomi-zation(MR)methodology.Methods Employing the inverse variance weighted(IVW)method in conjunction with six distinct MR methodologies,and utilizing summary data from genome-wide association studies(GWAS),the causal rela-tionships between visceral adipose tissue(VAT)and lung diseases,including chronic obstructive pulmonary disease,sleep apnea,lung cancer,pneumonia,pulmonary embolism,idiopathic pulmonary fibrosis and tuberculosis,were assessed.Sensitivity analysis was performed using the leave-one-out method,Cochran's Q test,MR-Egger regression intercept term test,and MR-PRESSO test to evaluate the heterogeneity,pleiotropy,and stability of the instrumental varia-bles.Results The results of the IVW method indicated that genetically predicted higher VAT was causally associated with higher occurrence risks of chronic obstructive pulmonary disease(OR=1.56,95％CI:1.33-1.84,P＜0.001),sleep apnea(OR=1.76,95％CI:1.53-2.03,P＜0.001),lung cancer(OR=1.39,95％CI:1.23-1.58,P＜0.001),and pneumonia(OR=1.22,95％CI:1.15-1.30,P＜0.001).Except for MR-Egger,the results of the other four MR methods were consistent with the main analysis results.In addition,there was evidence suggested that higher VAT would increase the occurrence risks of pulmonary embolism(OR=1.18,95％CI:1.04-1.34,P=0.009)and idiopathic pulmonary fibrosis(OR=1.00,95％CI:1.00-1.00,P=0.011).Conclusion VAT accumulation may increase the occurrence risks of chronic obstructive pulmona-ry disease,sleep apnea,lung cancer,pneumonia,pulmonary embolism and idiopathic pulmonary fibrosis.
NETL
NSTL
万方数据