| Literature DB >> 24241537 |
Klaus Bønnelykke1, Patrick Sleiman2, Kasper Nielsen3, Eskil Kreiner-Møller4, Josep M Mercader5, Danielle Belgrave6, Herman T den Dekker7, Anders Husby8, Astrid Sevelsted4, Grissel Faura-Tellez9, Li Juel Mortensen4, Lavinia Paternoster10, Richard Flaaten4, Anne Mølgaard4, David E Smart11, Philip F Thomsen12, Morten A Rasmussen13, Silvia Bonàs-Guarch5, Claus Holst14, Ellen A Nohr15, Rachita Yadav16, Michael E March17, Thomas Blicher18, Peter M Lackie19, Vincent W V Jaddoe20, Angela Simpson21, John W Holloway19, Liesbeth Duijts22, Adnan Custovic21, Donna E Davies11, David Torrents23, Ramneek Gupta16, Mads V Hollegaard24, David M Hougaard24, Hakon Hakonarson2, Hans Bisgaard25.
Abstract
Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes.Entities:
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Year: 2013 PMID： 24241537 DOI： 10.1038/ng.2830
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330