Assessing the Causal Relationship between Chronic Obstructive Pulmonary Disease and Tuberculosis: A Mendelian Randomization Study

Zhuo Wang,1,* Shuang Zhao,1,* Yiwu Zhou,2– 4 Yanqi He1 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Emergency Department, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Disaster Medical Center, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiwu Zhou, Email [email protected] Yanqi He, Email [email protected]: 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.Methods: 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.Results: 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).Conclusion: 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.Keywords: chronic obstructive pulmonary disease, tuberculosis, Mendelian randomization study