Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 130, Issue 1, Pages 83-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2012.03.020
Keywords
Asthma; pediatrics; age of onset; asthma genetics; C1orf100; genome-wide association study; pediatric asthma
Categories
Funding
- US National Institutes of Health [HL04370, HL66289]
- National Heart, Lung, and Blood Institute and General Clinical Research Center from the National Center for Research Resources [M01RR00051, M01RR0099718-24, M01RR02719-14, RR00036]
- European Commission as part of GA-BRIEL [018996, LSH-2004-1.2.5-1]
- Wellcome Trust [WT084703MA]
- US Federal Government from the National Heart, Lung, and Blood Institute [N02-HL-6 4278]
- Swedish Research Council
- Stockholm County Council
- Centre for Allergy Research, Karolinska Institutet
- Swedish Heart Lung Foundation
- Swedish Fulbright Commission
- Riksbankens Jubileumsfond
- Erik Ronnberg's scholarship
- National Heart, Lung, and Blood Institute
- Childhood Asthma Management Program (CAMP)
- Childhood Asthma Research and Education (CARE) network
- Abbott
- National Institutes of Health
- National Heart Lung and Blood Institute
- [NO1-HR-16044]
- [16045]
- [16046]
- [16047]
- [16048]
- [16049]
- [16050]
- [16051]
- [16052]
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Background: Childhood asthma is a complex disease with known heritability and phenotypic diversity. Although an earlier onset has been associated with more severe disease, there has been no genome-wide association study of the age of onset of asthma in children. Objective: We sought to identify genetic variants associated with earlier onset of childhood asthma. Methods: We conducted the first genome-wide association study of the age of onset of childhood asthma among participants in the Childhood Asthma Management Program (CAMP) and used 3 independent cohorts from North America, Costa Rica, and Sweden for replication. Results: Two single nucleotide polymorphisms (SNPs) were associated with earlier onset of asthma in the combined analysis of CAMP and the replication cohorts: rs9815663 (Fisher P = 2.31 x 10(-8)) and rs7927044 (P = 6.54 x 10(-9)). Of these 2 SNPs, rs9815663 was also significantly associated with earlier asthma onset in an analysis including only the replication cohorts. Ten SNPs in linkage disequilibrium with rs9815663 were also associated with earlier asthma onset (2.24 x 10(-7) < P < 8.22 x 10(-6)). Having 1 or more risk alleles of the 2 SNPs of interest (rs9815663 and rs7927044) was associated with lower lung function and higher asthma medication use during 4 years of follow-up in CAMP. Conclusions: We have identified 2 SNPs associated with earlier onset of childhood asthma in 4 independent cohorts. (J Allergy Clin Immunol 2012;130:83-90.)
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