Causal Role of Immune Cells in Chronic Obstructive Pulmonary Disease: A Two-Sample Mendelian Randomization Study

Abstract

AbstractAccumulating evidence has highlighted the importance of immune cells in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the understanding of the causal association between immunity and COPD remains incomplete due to the existence of confounding variables. In this study, we employed a two-sample Mendelian randomization (MR) analysis, utilizing the genome-wide association study database, to investigate the causal association between 731 immune-cell signatures and the susceptibility to COPD from a host genetics perspective. To validate the consistency of our findings, we utilized MR analysis results of lung function data to assess directional concordance. Furthermore, we employed MR-Egger intercept tests, Cochrane’s Q test, MR-PRESSO global test, and "leave-one-out" sensitivity analyses to evaluate the presence of horizontal pleiotropy, heterogeneity, and stability, respectively. Inverse variance weighting results showed that seven immune phenotypes were associated with the risk of COPD. Analyses of heterogeneity and pleiotropy analysis confirmed the reliability of MR results. These results highlight the interactions between the immune system and the lungs. Further investigations into their mechanisms are necessary and will contribute to inform targeted prevention strategies for COPD.

Keywords

• Chronic obstructive pulmonary disease
• immune cells
• immunophenotypes
• Mendelian randomization