Genome-wide association study of the age of onset of childhood asthma

Erick Forno, Jessica Lasky-Su, Blanca Himes, Judie Howrylak, Clare Ramsey, John Brehm, Barbara Klanderman, John Ziniti, Erik Melén, Goran Pershagen, Magnus Wickman, Fernando Martinez, Dave Mauger, Christine Sorkness, Kelan Tantisira, Benjamin A. Raby, Scott T. Weiss, Juan C. Celedón

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37 Citations (Scopus)

Abstract

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 × 10-8) and rs7927044 (P = 6.54 × 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 × 10-7 < P < 8.22 × 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.

Original languageEnglish (US)
Pages (from-to)83-90.e4
JournalJournal of Allergy and Clinical Immunology
Volume130
Issue number1
DOIs
StatePublished - Jul 2012

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Genome-Wide Association Study
Age of Onset
Asthma
Single Nucleotide Polymorphism
Costa Rica
Linkage Disequilibrium
North America
Sweden
Alleles

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Forno, Erick ; Lasky-Su, Jessica ; Himes, Blanca ; Howrylak, Judie ; Ramsey, Clare ; Brehm, John ; Klanderman, Barbara ; Ziniti, John ; Melén, Erik ; Pershagen, Goran ; Wickman, Magnus ; Martinez, Fernando ; Mauger, Dave ; Sorkness, Christine ; Tantisira, Kelan ; Raby, Benjamin A. ; Weiss, Scott T. ; Celedón, Juan C. / Genome-wide association study of the age of onset of childhood asthma. In: Journal of Allergy and Clinical Immunology. 2012 ; Vol. 130, No. 1. pp. 83-90.e4.
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abstract = "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 × 10-8) and rs7927044 (P = 6.54 × 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 × 10-7 < P < 8.22 × 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.",
author = "Erick Forno and Jessica Lasky-Su and Blanca Himes and Judie Howrylak and Clare Ramsey and John Brehm and Barbara Klanderman and John Ziniti and Erik Mel{\'e}n and Goran Pershagen and Magnus Wickman and Fernando Martinez and Dave Mauger and Christine Sorkness and Kelan Tantisira and Raby, {Benjamin A.} and Weiss, {Scott T.} and Celed{\'o}n, {Juan C.}",
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Forno, E, Lasky-Su, J, Himes, B, Howrylak, J, Ramsey, C, Brehm, J, Klanderman, B, Ziniti, J, Melén, E, Pershagen, G, Wickman, M, Martinez, F, Mauger, D, Sorkness, C, Tantisira, K, Raby, BA, Weiss, ST & Celedón, JC 2012, 'Genome-wide association study of the age of onset of childhood asthma', Journal of Allergy and Clinical Immunology, vol. 130, no. 1, pp. 83-90.e4. https://doi.org/10.1016/j.jaci.2012.03.020

Genome-wide association study of the age of onset of childhood asthma. / Forno, Erick; Lasky-Su, Jessica; Himes, Blanca; Howrylak, Judie; Ramsey, Clare; Brehm, John; Klanderman, Barbara; Ziniti, John; Melén, Erik; Pershagen, Goran; Wickman, Magnus; Martinez, Fernando; Mauger, Dave; Sorkness, Christine; Tantisira, Kelan; Raby, Benjamin A.; Weiss, Scott T.; Celedón, Juan C.

In: Journal of Allergy and Clinical Immunology, Vol. 130, No. 1, 07.2012, p. 83-90.e4.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association study of the age of onset of childhood asthma

AU - Forno, Erick

AU - Lasky-Su, Jessica

AU - Himes, Blanca

AU - Howrylak, Judie

AU - Ramsey, Clare

AU - Brehm, John

AU - Klanderman, Barbara

AU - Ziniti, John

AU - Melén, Erik

AU - Pershagen, Goran

AU - Wickman, Magnus

AU - Martinez, Fernando

AU - Mauger, Dave

AU - Sorkness, Christine

AU - Tantisira, Kelan

AU - Raby, Benjamin A.

AU - Weiss, Scott T.

AU - Celedón, Juan C.

PY - 2012/7

Y1 - 2012/7

N2 - 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 × 10-8) and rs7927044 (P = 6.54 × 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 × 10-7 < P < 8.22 × 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.

AB - 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 × 10-8) and rs7927044 (P = 6.54 × 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 × 10-7 < P < 8.22 × 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.

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