内脏脂肪组织与肺部疾病的孟德尔随机化研究

Mendelian randomization study of visceral adipose tissue and lung diseases

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,GWAS)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。

Objective To investigate the causal relationship between obesity and lung diseases using Mendelian randomization(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 relationships 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,Cochrans Q test,MR-Egger regression intercept term test,and MR-PRESSO test to evaluate the heterogeneity,pleiotropy,and stability of the instrumental variables.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 pulmonary disease,sleep apnea,lung cancer,pneumonia,pulmonary embolism and idiopathic pulmonary fibrosis.