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

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  • Anders U. Eliasen
  • Casper Emil T. Pedersen
  • Ni Wang
  • Matteo Soverini
  • Amelie Fritz
  • Andréanne Morin
  • Jette Bork-Jensen
  • Preben B. Mortensen
  • David M. Hougaard
  • Jonas Bybjerg-Grauholm
  • Marie Bækvad-Hansen
  • Ole Mors
  • Anders D. Børglum
  • Esben Agerbo
  • Cilla Söderhall
  • Matthew C. Altman
  • Anna H. Thysen
  • Chris G. McKennan
  • James E. Gern
  • Carole Ober
  • Hans Bisgaard
  • Anders G. Pedersen

Background: Asthma with severe exacerbation is one of the most common causes of hospitalization among young children. Exacerbations are typically triggered by respiratory infections, but the host factors causing recurrent infections and exacerbations in some children are poorly understood. As a result, current treatment options and preventive measures are inadequate. Objective: We sought to identify genetic interaction associated with the development of childhood asthma. Methods: We performed an exhaustive search for pairwise interaction between genetic single nucleotide polymorphisms using 1204 cases of a specific phenotype of early childhood asthma with severe exacerbations in patients aged 2 to 6 years combined with 5328 nonasthmatic controls. Replication was attempted in 3 independent populations, and potential underlying immune mechanisms were investigated in the COPSAC2010 and COPSAC2000 birth cohorts. Results: We found evidence of interaction, including replication in independent populations, between the known childhood asthma loci CDHR3 and GSDMB. The effect of CDHR3 was dependent on the GSDMB genotype, and this interaction was more pronounced for severe and early onset of disease. Blood immune analyses suggested a mechanism related to increased IL-17A production after viral stimulation. Conclusions: We found evidence of interaction between CDHR3 and GSDMB in development of early childhood asthma, possibly related to increased IL-17A response to viral infections. This study demonstrates the importance of focusing on specific disease subtypes for understanding the genetic mechanisms of asthma.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Issue number3
Pages (from-to)622-630
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 American Academy of Allergy, Asthma & Immunology

    Research areas

  • Childhood asthma, early life, genetic interactions, immunology

ID: 308125958