Causal Links between Immune Cells and Asthma: Insights from a Mendelian Randomization Analysis.

OBJECTIVES: Recent studies suggest immunophenotypes may play a role in asthma, but their causal relationship has not been thoroughly examined.

METHODS: We used single nucleotide polymorphism (SNP)-derived instrumental variables. Summary data from 731 immune cell profiles and asthma cases were analyzed from genome-wide association studies (GWAS) of European populations. Mendelian Randomization (MR) analyses included inverse variance weighted (IVW), weighted median, and MR-Egger methods. Pleiotropy was assessed using the MR-Egger intercept and MR pleiotropy residual sum and outlier (MR-PRESSO) tests. Reverse MR analysis explored bidirectional causation between asthma and immunophenotypes. All statistical analyses were conducted using R software.

RESULTS: MR analysis identified 108 immune signatures potentially contributing to asthma. Two immunophenotypes were significantly associated with asthma risk: CD4+ secreting Treg cells in allergic asthma (ORIVW =1.078; 95% CI: 1.036-1.122; PIVW =0.0002) and IgD + CD38- %lymphocyte cells in non-allergic asthma (ORIVW =1.123; 95% CI: 1.057-1.194; PIVW =0.0002).

CONCLUSIONS: This study highlights the causal associations between specific immunophenotypes and asthma risk, providing new insights into asthma pathogenesis.