Causal role of immune cells in asthma: a Mendelian randomization study.

ABSTRACT

BACKGROUND: Immune cells may have a significant role in the pathophysiology of asthma, according to increasing evidence, although it is yet unclear how immune cells cause asthma. Therefore, we aimed to use Mendelian randomization (MR) methods to investigate this causal relationship. METHODS: This study explored the causal effects between immune cells and asthma using a two-sample MR technique. Using publicly available genetic data, the causal connection between asthma risk and 731 immune cell phenotypes was investigated. Sensitivity analysis guaranteed the results' stability. To further evaluate the existence of reverse causality, we employed reverse MR analysis. RESULTS: According to the inverse-variance weighted (IVW) method, five immune cell phenotypes were found to be statistically significantly associated with asthma risk (p < 0.001). Among them, TCRgd %T cell (OR = 0.968, 95%CI = 0.951 - 0.986), TCRgd %lymphocyte (OR = 0.978, 95%CI = 0.965 - 0.991), HLA DR + NK AC (OR = 0.966, 95% CI = 0.947 - 0.986) and CD3 on CD4 Treg (OR = 0.956, 95%CI= 0.931 - 0.981), four phenotypes that resulted in a decreased risk of asthma. CD25 on transitional (OR = 1.033, 95%CI = 1.014 - 1.052) resulted in an increased risk of asthma. Reverse MR analysis revealed that asthma increases HLA DR + NK AC levels (p < 0.05). CONCLUSION: The results of MR analysis showed a causal relationship between immune cell phenotype and asthma risk, which provides a direction for future asthma treatment.