Causal Associations Between Chronic Obstructive Pulmonary Disease and Common Comorbidities: Evidence from Comprehensive Genetic Methods.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease with high morbidity and mortality worldwide. Observational studies have shown correlations between common extrapulmonary comorbidities and COPD, but the existence of correlations does not necessarily prove a causal association. Therefore, causal relationships between diseases need to be explored by means of causal inference methods.

Materials And Methods: Genetic correlation and two-sample Mendelian randomization (MR) analysis were explored to assess the causal relationship between exposures and outcomes with the genome-wide association studies (GWAS) dataset. Different sensitivity analyses were conducted to verify the robustness and consistency of results.

Results: The linkage disequilibrium score regression showed that cardiovascular disease (CVD), hypertension (HTN) and type 2 diabetes mellitus (T2DM) were significantly genetically associated with COPD. T2DM and HTN were found to have a positive causal effect on COPD. The odds ratio (OR) of T2DM on COPD was 1.111 (95% CI, 1.063-1.160; P<0.0001) and that of HTN on COPD was 1.125 (95% CI, 1.084-1.167; P < 0.0001). Similar results were verified by different MR methods. Furthermore, COPD had a positive causal effect on T2DM (OR 1.152 (95% CI, 1.064-1.246; P=0.0005)).

Conclusion: Our findings provided evidence for the causal association between HTN, T2DM and COPD, which would render new insights into the pathogenesis, prevention and intervention for COPD.