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

Abstract

Accumulating 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

Ethics statement

The summary-level data used in this study are de-identified public data and are available for download. Each GWAS involved in this study was ethically approved by the respective institutions.

Data availability

The data that supports the findings of this study are available upon reasonable request from the corresponding author.

Conflicts of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflicts with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author contributions

Qian Zhang and Xinru Xiao designed the study and wrote the manuscript. Xinru Xiao, Ziqi Ding, and Yujia Shi analyzed data and drew the figures. All authors read and approved the final manuscript.

Additional information

Funding

This study was supported by grants from the Jiangsu province social development project (BE2020651 to Q.Z.), and in part from the Changzhou High-Level Medical Talents Training Project (2022CZLJ013 to Q.Z.), the Nanjing Medical University Changzhou Medical Center Research Project (CMCB202214, CMCC202303 to Q.Z.).