Mendelian Randomization Analysis of Immune Cells and Asthma

Abstract

Background: The immune cells play a substantial role in the development and advancement of asthma. Therefore, we utilized mendelian randomization (MR) analysis to investigate the correlation between immune cells and asthma. Objective: Given that immune cells play a crucial role in the onset and progression of the condition, this study aimed to elucidate the unclear links between immune cells and asthma. Methods: The publicly available genetic data regarding asthma were obtained from the IEU database, and genetic variation points were selected as instrumental variables (IV_S). Moreover, genetic information concerning immune cells was obtained from published literature. We used five different methods for dual sample mendelian randomization (MR) analysis, including inverse variance weighted (IVW), weighted median (WMI), MR-Egger regression, simple mode (SM), and weighted mode (WM). Furthermore, sensitivity analysis was utilized to examine the heterogeneity, horizontal pleiotropy, and stability of the outcomes. Results: IVW results showed that B-cell Activating factor of the TNF family receptor (BAFF–R) on B cell, BAFF–R on IgD^- CD27^- B cell, BAFF–R on IgD⁺ CD24^- B cell, BAFF–R on IgD⁺ CD38^dim B cell, CD33^br HLA DR⁺ CD14^dim myeloid cell, CD25 on B cell, CD25 on IgD⁺ CD24^- B cell, CD25 on IgD⁺ CD38^- naive B cell, CD25 on naive-mature B cell, CD25 on transitional B cell, CD33 on basophil, CD33 on CD14⁺ monocyte, CD33^dim HLA DR⁺ CD11b^- myeloid cell, CD33 on CD66b⁺ myeloid cell, CD38 on IgD^- CD38^dim B cell, CD86 on myeloid dendritic cells (DC), HLA DR on CD14^- CD16⁺ monocyte, IgD⁺ CD38^br lymphocyte, and transitional lymphocyte may be the risk factors of asthma. Moreover, CD11b on CD14⁺ monocyte, CD24 on IgD⁺ CD38^br B cell, CD28 on CD45RA⁺ CD4⁺ Treg, CD45 on NK, HLA DR⁺ CD3^- NK, HLA DR⁺ NK cell, IgD^- CD38^- B cell, PDL–1 on CD14⁺ CD16^- monocyte, and plasmacytoid dendritic cells (DC) were identified as protective factors for asthma. Conclusion: This study explored the causal relationship between asthma and immune cells and identified immune cells correlated with asthma development. These immune cells may become new biomarkers or therapeutic targets, provide better treatment options for the prevention and treatment of asthma, and promote the understanding of asthma.