Causal Relationships Between Immune Cell Traits, Plasma Metabolites, and Asthma: A Two-Step, Two-Sample Mendelian...

Considerable evidence suggests a strong link between immune cell traits (ICTs) and asthma development via plasma metabolites (PMs), but the causality between ICTs and asthma is still unclear, mainly due to issues like selection bias. Our research was designed to investigate the causality between ICTs, PMs, and asthma and to provide a clearer explanation of these relationships.

Utilizing the GWAS database, this study employed a two-step, two-sample Mendelian randomization (MR) approach and the inverse variance weighted (IVW) method to investigate the causality between ICTs and asthma, as well as between PMs and asthma. Lastly, we calculated the mediated proportion of PMs as mediators in the link between ICTs and asthma.

Excluding heterogeneity and pleiotropy, MR analysis identified 13 ICTs (CD14 on CD33br HLA DR+ CD14dim, etc.) and asthma causality, and no reverse causality was observed. In addition, 27 PMs (androsterone sulfate levels, succinate levels, etc.) were also causally associated with asthma. Mediate MR indicated -9.81% (-1.2%, -18.4%) of the effect of CD24 on IgD+ CD38br on asthma is mediated by S-methylcysteine sulfoxide levels, with a mediated effect value (p = 0.006) is 0.003 (0.0004, 0.006); 21.4% (6.2%, -36.6%) of the effect of CD3 on CD28+ CD4+ on asthma is mediated by 1-myristoyl-2-arachidonoyl-GPC (14:0/20:4) levels, with a mediated effect value (p = 0.025) is 0.004 (0.001, 0.007).

We identified two pathways by which ICTs can impact asthma through PMs, which might help in identifying potential targets for personalized treatment approaches.