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Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB

Anders U Eliasen1, Casper Emil T Pedersen2, Morten A Rasmussen3

  • 1Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, Kongens Lyngby, Denmark.

The Journal of Allergy and Clinical Immunology
|April 5, 2022
PubMed

Insights

Genetic interactions between CDHR3 and GSDMB influence childhood asthma development, particularly severe exacerbations. This finding may lead to better treatments for early-onset asthma linked to viral infections.

Area of Science:

  • Genetics
  • Immunology
  • Pediatrics

Background:

  • Severe asthma exacerbations frequently hospitalize young children.
  • Triggers are often respiratory infections, but host factors remain unclear.
  • Current asthma treatments and prevention are insufficient.

Purpose of the Study:

  • Identify genetic interactions linked to childhood asthma.
  • Focus on early childhood asthma with severe exacerbations.

Main Methods:

  • Analyzed single nucleotide polymorphism interactions in 1204 early childhood asthma cases and 5328 controls.
  • Replicated findings in 3 independent populations.
  • Investigated immune mechanisms in birth cohorts.

Main Results:

  • Found replicated interaction between CDHR3 and GSDMB loci.
  • CDHR3's effect depended on GSDMB genotype, especially in severe, early-onset disease.
  • Immune analysis indicated increased IL-17A production post-viral stimulation.

Conclusions:

  • CDHR3 and GSDMB interaction contributes to early childhood asthma.
  • Mechanism may involve heightened IL-17A response to viral infections.
  • Subtyping asthma is crucial for understanding genetic drivers.
Abstract

Keywords:
Childhood asthmaearly lifegenetic interactionsimmunology

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