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

Area of Science:

• Immunology
• Genetics
• Metabolomics

Background:

• Asthma development is strongly linked to immune cell traits (ICTs) and plasma metabolites (PMs).
• Causality between ICTs, PMs, and asthma remains unclear due to potential biases.
• This research aims to clarify these complex relationships.

Purpose of the Study:

• To investigate the causal relationships between ICTs and asthma.
• To explore the causal role of PMs in asthma development.
• To determine the mediating effect of PMs in the ICT-asthma pathway.

Main Methods:

• Employed a two-step, two-sample Mendelian randomization (MR) approach using GWAS data.
• Utilized the inverse variance weighted (IVW) method to assess causality.
• Calculated the proportion of PMs mediating the effect of ICTs on asthma.

Main Results:

• Identified 13 ICTs causally linked to asthma, with no evidence of reverse causality.
• Found 27 PMs causally associated with asthma.
• Demonstrated specific mediation pathways, e.g., S-methylcysteine sulfoxide mediating the effect of CD24 on IgD+ CD38br on asthma.

Conclusions:

• Identified two distinct pathways through which ICTs influence asthma via PMs.
• These findings may inform the development of personalized asthma treatment strategies.
• Highlights potential novel therapeutic targets for asthma management.