Childhood Asthma: Novel Susceptibility Gene Identified Interview Invitation
Klaus Bønnelykke MD, PhD

The Faculty of Health Sciences University of Copenhagen
The Danish Pediatric Asthma Center Copenhagen University Hospital
Gentofte Ledreborg Alle 34 DK-2820 Copenhagen Denmark What are the main findings of the study?

Answer: First, we identified CDHR3 as a novel susceptibility gene. This is likely to represent a yet unknown mechanism of childhood asthma. Based on the replication birth cohorts this gene particularly plays a role for severe asthma attacks in the first 2 years of life while it is not associated with adult-onset asthma. This suggests a specific mechanism of asthma in early childhood.

Second, we found very strong results (much larger effect sizes than found in previous genome-wide association studies) for known asthma genes, particularly for the children with most frequent asthma attacks. This shows that genetics play a very strong role for these children. Subsequent calculations suggest that the majority of cases with severe asthma are caused by the 5 most significant genes/loci in this study. This means that focusing asthma research on these 5 genetic loci and their effects has the potential to prevent the majority of incidences of severe asthma in early childhood. Were any of the findings unexpected?

Answer: We were surprised to see so strong results for the already known asthma-genes. From a research perspective this shows the potential (and cost-effectiveness) of focusing on this specific type of disease. By studying these 1,200 children with asthma we got very significant results and similar number of findings as the previously largest genome-wide association study with 10.000 individuals with asthma. What should clinicians and patients take away from your report?

Answer:Asthma is a heterogeneous disease and this is probably one main reason for the limited effect of current asthma medications for preventing and treating asthma attacks in young children. Discovery of the genes causing asthma in early childhood is one important step in understanding the disease. Hopefully this will improve prevention and treatment of disease in the future. What recommendations do you have for future research as a result of this study?

Answer: Future studies should focus on asthma with severe attacks in early childhood. This is a subtype of disease where we need better understanding. Also, our study suggest that this is a strong approach for learning more about asthma mechanisms in general.



A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations
Klaus Bønnelykke, Patrick Sleiman, Kasper Nielsen, Eskil Kreiner-Møller, Josep M Mercader, Danielle Belgrave, Herman T den Dekker, Anders Husby, Astrid Sevelsted, Grissel Faura-Tellez, Li Juel Mortensen, Lavinia Paternoster, Richard Flaaten, Anne Mølgaard, David E Smart, Philip F Thomsen, Morten A Rasmussen, Silvia Bonàs-Guarch, Claus Holst, Ellen A Nohr, Rachita Yadav, Michael E March, Thomas Blicher, Peter M Lackie, Vincent W V Jaddoe, Angela Simpson, John W Holloway, Liesbeth Duijts, Adnan Custovic, Donna E Davies, David Torrents, Ramneek Gupta, Mads V Hollegaard, David M Hougaard, Hakon Hakonarson & Hans Bisgaard

Nature Genetics (2013) doi:10.1038/ng.2830

Received 27 May 2013 Accepted 28 October 2013 Published online 17 November 2013