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

Anders U. Eliasen, Casper Emil T. Pedersen, Morten A. Rasmussen, Ni Wang, Matteo Soverini, Amelie Fritz, Jakob Stokholm, Bo L. Chawes, Andreanna Morin, Jette Bork-Jensen, Niels Grarup, Oluf Pedersen, Torben Hansen, Allan Linneberg, Preben B. Mortensen, David M. Hougaard, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, Ole Mors, Merete NordentoftAnders D. Børglum, Thomas Werge, Esben Agerbo, Cilla Söderhall, Matthew C. Altman, Anna H. Thysen, Chris G. McKennan, Susanne Brix, James E. Gern, Carole Ober, Tarunveer S. Ahluwalia, Hans Bisgaard, Anders G. Pedersen*, Klaus Bønnelykke*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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: To identify genetic interaction associated with the development of childhood asthma.

Methods: We performed an exhaustive search for pairwise interaction between genetic variants, single nucleotide polymorphisms (SNPs), using 1204 cases with a specific phenotype of early childhood asthma with severe exacerbations (age 2-6 years) combined with 5328 non-asthmatic 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


  • Childhood asthma
  • Genetic interactions
  • Early-life
  • Immunology


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