Journal article
A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations
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.
Language: | English |
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Publisher: | Nature Publishing Group US |
Year: | 2014 |
Pages: | 51-55 |
ISSN: | 15461718 and 10614036 |
Types: | Journal article |
DOI: | 10.1038/ng.2830 |
ORCIDs: | 0000-0001-7431-5206 , 0000-0003-4131-7592 , Nielsen, Kasper , Gupta, Ramneek and 0000-0003-1204-2438 |
Acid Anhydride Hydrolases Asthma CDHR3 protein, human Cadherin Related Proteins Cadherins Case-Control Studies Child Child, Preschool Chromosomes, Human, Pair 17 DNA Repair Enzymes DNA-Binding Proteins Denmark Female GSDMB protein, human Genetic Predisposition to Disease Genome-Wide Association Study Humans IL1RL1 protein, human IL33 protein, human Interleukin-1 Receptor-Like 1 Protein Interleukin-33 Interleukins Male Membrane Proteins Models, Molecular Neoplasm Proteins Polymorphism, Single Nucleotide Protein Conformation RAD50 protein, human Receptors, Cell Surface