Causal Involvement of Immune Cells in Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Study

Abstract

Tiefa Guan,1,2,* Yibing Qin,3,* Nini Qu,3 Yushuo Pan1 1First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nini Qu, Email [email protected]: The immune cells play a substantial role in the development and progression of chronic obstructive pulmonary disease (COPD). We aim to investigate the causal involvement of immune cells in COPD via a Mendelian randomization (MR) analysis.Methods: Published genome-wide association studies (GWAS) statistics on immune cells were analyzed, with genetic variants identified as instrumental variables (IVs). Inverse-variance weighting (IVW), weighted median, and MR-Egger regression methods were employed, along with simple mode and weighted mode adopted in the two-sample MR analysis. Sensitivity analysis was conducted to examine the heterogeneity, horizontal pleiotropy, and stability of the causal relationship.Results: IVW results suggested that CCR2 on CD62L+ plasmacytoid dendritic cells (DC), CCR2 on plasmacytoid DC, CD11b on CD66b++ myeloid cells, CD19 on CD20− CD38− CD24+ memory B cell subset, CD25 on transitional B cells, and CD25++CD8br %CD8br T cells were risk factors for the development of COPD. Besides, CD127 on effector memory-like cytotoxic T lymphocytes lacking expression of co-stimulatory molecule 28 (CD28-EM CTLs) and HLA DR+ NK ACs expressing human leukocyte antigen DR molecules while being natural killer cells (%NK ACs) were protective factors for COPD.Conclusion: This study unveiled a causal relationship between immune cell phenotype and COPD. These findings offer new insights for the prevention and treatment of COPD using COPD-associated immune cells.Keywords: chronic obstructive pulmonary disease, immune cells, causal inference, Mendelian randomization

Keywords

• chronic obstructive pulmonary disease
• immune cells
• causal inference
• mendelian randomization