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A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations.

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

Nature genetics. 2014;46(1):51-5.

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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.

Bibliographic metadata

Type of resource:
Content type:
Publication status:
Accepted
Publication type:
Publication form:
Published date:
Language:
eng
Journal title:
Abbreviated journal title:
ISSN:
Place of publication:
United States
Volume:
46
Issue:
1
Pagination:
51-5
Digital Object Identifier:
10.1038/ng.2830
Pubmed Identifier:
24241537
Pii Identifier:
ng.2830
Attached files embargo period:
Immediate release
Attached files release date:
26th August, 2014
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:230117
Created by:
Custovic, Adnan
Created:
28th July, 2014, 15:53:29
Last modified by:
Heydon, Kirsty
Last modified:
29th September, 2015, 13:27:13

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