Leveraging gene-environment interactions and endotypes for asthma gene discovery

Area of Science:

• Genetics
• Environmental Health
• Immunology

Background:

• Asthma is a complex, heterogeneous disease influenced by gene-environment interactions (GEIs).
• Genetic studies have identified some asthma risk alleles, but they explain limited heritability.
• Early-life environmental exposures significantly impact asthma development.

Purpose of the Study:

• To review evidence supporting the hypothesis that specific asthma phenotypes and GEIs improve asthma gene detection.
• To discuss challenges and advantages of studying GEIs in asthma pathogenesis.
• To highlight opportunities for understanding asthma heterogeneity and improving treatments.

Main Methods:

• Review of existing evidence on asthma phenotypes and GEIs.
• Discussion of studying gene-environment interactions in clinical birth cohorts and cell models.
• Analysis of approaches to dissect context-specific genotypic risks and prioritize variants.

Main Results:

• Focusing on specific asthma phenotypes (e.g., severe childhood asthma) and exposures (e.g., rhinovirus) aids in identifying asthma susceptibility genes.
• Studying GEIs in relevant models helps understand context-specific genetic risks and disease pathways.
• Prioritizing variants through GEI analysis can advance understanding of asthma pathogenesis.

Conclusions:

• Investigating GEIs in specific asthma subgroups offers significant opportunities for advancing asthma research.
• This approach can improve the understanding of asthma heterogeneity and underlying mechanisms.
• Ultimately, this can lead to better prevention and treatment strategies for asthma.