Journal of Thoracic Disease · Sep 29, 2026

Correlation between chronic obstructive pulmonary disease and comorbidities-a systematic analysis integrating global burden of disease and mendelian randomization study

By Feng H, Jiao C, Lv W et al.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) frequently coexists with multiple comorbidities. However, the long-term trends, regional disparities, and potential causal relationships in the global burden of these comorbidities remain to be systematically elucidated. This study aimed to characterize the disease burden of common comorbidities in patients with COPD and to assess the potential causal relationships between these comorbidities and COPD. METHODS: This study integrated data from the Global Burden of Disease Study 2023 (GBD 2023) and conducted two-sample Mendelian randomization (MR) analyses. Based on GBD data from 1990 to 2023, we performed descriptive burden assessment, Das Gupta decomposition, Bayesian age-period-cohort modelling, exploratory correlation analysis, and formal age-interaction regression. Using summary statistics from the FinnGen consortium, we evaluated bidirectional genetic associations between COPD and various comorbidities primarily via the inverse variance weighted (IVW) method with false discovery rate (FDR) correction for multiple comparisons. The comorbidities of focus included asthma, anxiety disorders, major depressive disorder, pulmonary hypertension, hypertensive heart disease, ischemic heart disease, musculoskeletal disorders, osteoporosis, and respiratory tract cancers. RESULTS: The absolute burden of comorbidities in COPD continued to increase, albeit driven by distinct factors. Population aging and growth were identified as the primary drivers for the rising burden of several COPD comorbidities, such as ischemic heart disease and musculoskeletal disorders. Significant regional inequalities were observed in disease distribution: high Socio-demographic Index (SDI) regions bore a heavier burden of musculoskeletal and mental disorders, whereas middle and low SDI regions exhibited more pronounced mortality and disability-adjusted life years (DALYs) attributable to ischemic heart disease. Formal interaction models demonstrated significant age heterogeneity in the ecological associations between COPD prevalence and all eight comorbidities after Benjamini-Hochberg correction (all q ≤0.028). MR analyses provided evidence supporting bidirectional genetic associations between COPD and specific comorbidities. Genetically predicted COPD was significantly associated with an increased risk of asthma and depression (FDR <0.05), and conversely, genetic susceptibility to asthma and depression was associated with a higher risk of developing COPD (FDR <0.05). CONCLUSIONS: The comorbidity patterns between COPD and its key concomitant conditions are influenced by multiple factors, including demographic structure, regional development levels, and shared biological mechanisms. Our findings underscore the necessity of shifting from a single-disease management model towards integrated care strategies that emphasize comorbidity screening and holistic patient management.

doi.org/10.21037/jtd-2026-1821Open accessPubMed 42997002Populations