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山东大学学报 (医学版) ›› 2024, Vol. 62 ›› Issue (7): 48-55.doi: 10.6040/j.issn.1671-7554.0.2024.0534

• 呼吸系统疾病精准诊疗专题 • 上一篇    下一篇

内脏脂肪组织与肺部疾病的孟德尔随机化研究

冯悦1,2,俞一凡1,2,吴思佳1,2,李洪凯1,2,薛付忠1,2   

  1. 1.山东大学齐鲁医学院公共卫生学院生物统计学系, 山东 济南 250012;2.国家健康医疗大数据研究院, 山东 济南 250003
  • 发布日期:2024-09-20
  • 通讯作者: 薛付忠. E-mail:xuefzh@sdu.edu.cn
  • 基金资助:
    国家自然科学基金项目(82173625)

Mendelian randomization study of visceral adipose tissue and lung diseases

FENG Yue1,2, YU Yifan1,2, WU Sijia1,2, LI Hongkai1,2, XUE Fuzhong1,2   

  1. 1. Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. National Institute of Health Data Science of China, Jinan 250003, Shandong, China
  • Published:2024-09-20

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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。

关键词: 内脏脂肪组织, 肺部疾病, 孟德尔随机化, 因果推断, 肥胖

Abstract: 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, Cochrans 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.

Key words: Visceral adipose tissue, Lung diseases, Mendelian randomization, Causal inference, Obesity

中图分类号: 

  • R574
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