Wang Zhuo, Zhao Shuang, Zhou Yiwu, He Yanqi
Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2025 May 5;20:1361-1371. doi: 10.2147/COPD.S511734. eCollection 2025.
Chronic obstructive pulmonary disease (COPD) and tuberculosis are both significant global public health challenges. The co-occurrence of these two diseases is frequently observed in clinical settings. However, their causal relationship remains unclear.
We utilized genome-wide association study (GWAS) datasets to conduct bidirectional two-sample Mendelian randomization and multivariable Mendelian randomization analyses. We first analyzed COPD data from the FinnGen consortium (n = 193,638) and tuberculosis data from a genetic association study (n = 484,598). In the second phase, we stratified COPD patients by age into the EARLY COPD group (Event_Age < 65) and the LATER COPD group (Event_Age ≥ 65) to explore their causal relationships with tuberculosis separately. We then validated these results using tuberculosis data from MRC-IEU (n = 462,933). Finally, smoking and COPD-related SNPs as instrumental variables were analyzed by multivariable Mendelian randomization to further investigate the association between COPD and tuberculosis. Multiple methods were used in the Mendelian analyses to ensure a comprehensive and rigorous investigation.
In the initial analysis phase utilizing the inverse variance weighting (IVW) method, tuberculosis showed no significant contribution to the incidence of COPD (IVW odds ratio (OR) = 0.9961; 95% confidence interval (CI) = 0.9828-1.0095; P = 0.564). Conversely, COPD appeared to significantly increase the risk of developing tuberculosis (IVW OR = 1.0008; 95% CI = 1.0001-1.0014; P = 0.015), particularly in patients under 65 (IVW OR = 1.0008; P = 0.011).
This Mendelian randomization analysis found that COPD may increase the risk of tuberculosis, while tuberculosis does not increase the risk of COPD, suggesting the necessity of enhancing prevention and screening efforts for tuberculosis among COPD patients, especially younger individuals.
慢性阻塞性肺疾病（COPD）和结核病都是重大的全球公共卫生挑战。在临床环境中经常观察到这两种疾病同时出现。然而，它们之间的因果关系仍不清楚。
我们利用全基因组关联研究（GWAS）数据集进行双向两样本孟德尔随机化和多变量孟德尔随机化分析。我们首先分析了来自芬兰基因联盟的COPD数据（n = 193,638）和来自一项基因关联研究的结核病数据（n = 484,598）。在第二阶段，我们将COPD患者按年龄分层为早期COPD组（发病年龄<65岁）和晚期COPD组（发病年龄≥65岁），以分别探讨它们与结核病的因果关系。然后，我们使用来自MRC-IEU的结核病数据（n = 462,933）对这些结果进行了验证。最后，通过多变量孟德尔随机化分析以吸烟和与COPD相关的单核苷酸多态性作为工具变量，进一步研究COPD与结核病之间的关联。在孟德尔分析中使用了多种方法，以确保进行全面而严谨的研究。
在利用逆方差加权（IVW）方法的初始分析阶段，结核病对COPD的发病率没有显著影响（IVW比值比（OR）= 0.9961；95%置信区间（CI）= 0.9828 - 1.0095；P = 0.564）。相反，COPD似乎显著增加了患结核病的风险（IVW OR = 1.0008；95% CI = 1.0001 - 1.0014；P = 0.015），特别是在65岁以下的患者中（IVW OR = 1.0008；P = 0.011）。
这项孟德尔随机化分析发现，COPD可能会增加患结核病的风险，而结核病不会增加患COPD的风险，这表明有必要加强对COPD患者，尤其是年轻患者的结核病预防和筛查工作。
