A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations
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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; Paternoster, Lavinia; Flaaten, Richard; Mølgaard, Anne; Smart, David E; Thomsen, Philip Francis; Rasmussen, Morten Arendt; Bonàs-Guarch, Silvia; Holst, Claus; Nohr, Ellen A.; Yadav, Rachita; March, Michael E; Blicher, Thomas Holberg; 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.
In: Nature Genetics, Vol. 46, 2014, p. 51-55.Research output: Contribution to journal › Letter › Research › peer-review
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T1 - A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations
AU - Bønnelykke, Klaus
AU - Sleiman, Patrick
AU - Nielsen, Kasper
AU - Kreiner-Møller, Eskil
AU - Mercader, Josep M
AU - Belgrave, Danielle
AU - den Dekker, Herman T
AU - Husby, Anders
AU - Sevelsted, Astrid
AU - Faura-Tellez, Grissel
AU - Paternoster, Lavinia
AU - Flaaten, Richard
AU - Mølgaard, Anne
AU - Smart, David E
AU - Thomsen, Philip Francis
AU - Rasmussen, Morten Arendt
AU - Bonàs-Guarch, Silvia
AU - Holst, Claus
AU - Nohr, Ellen A.
AU - Yadav, Rachita
AU - March, Michael E
AU - Blicher, Thomas Holberg
AU - Lackie, Peter M
AU - Jaddoe, Vincent W V
AU - Simpson, Angela
AU - Holloway, John W
AU - Duijts, Liesbeth
AU - Custovic, Adnan
AU - Davies, Donna E
AU - Torrents, David
AU - Gupta, Ramneek
AU - Hollegaard, Mads V.
AU - Hougaard, David M.
AU - Hakonarson, Hakon
AU - Bisgaard, Hans
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1038/ng.2830
DO - 10.1038/ng.2830
M3 - Letter
C2 - 24241537
VL - 46
SP - 51
EP - 55
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
ID: 76804021