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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:130

Article

Forno, Erick^1,2,4  Lasky-Su, Jessica^2,4  Himes, Blanca^2,4  Howrylak, Judie²  Ramsey, Clare⁵  Brehm, John^2,3,4  Klanderman, Barbara²  Ziniti, John²  Melen, Erik^2,6,7  Pershagen, Goran⁶  Wickman, Magnus^6,8  Martinez, Fernando⁹  Mauger, Dave¹⁰  Sorkness, Christine¹¹  Tantisira, Kelan^2,3,4  Raby, Benjamin A.^2,3,4  Weiss, Scott T.^2,4  Celedon, Juan C.¹² 

[1] Univ Miami, Dept Pediat, Div Pediat Pulmonol, Miami, FL 33136 USA

[2] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dept Med, Div Pulm Crit Care Med, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA USA

[5] Univ Manitoba, Dept Med, Winnipeg, MB, Canada

[6] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden

[7] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden

[8] Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden

[9] Univ Arizona, Dept Pediat, Tucson, AZ 85721 USA

[10] Penn State Hershey Coll Med, Hershey, PA USA

[11] Univ Wisconsin, Madison, WI USA

[12] Univ Pittsburgh, Sch Med, Div Pediat Pulm Med Allergy & Immunol, Childrens Hosp Pittsburgh,UPMC,Dept Pediat, Pittsburgh, PA 15260 USA

关键词: Asthma;    pediatrics;    age of onset;    asthma genetics;    C1orf100;    genome-wide association study;    pediatric asthma;   

DOI  :  10.1016/j.jaci.2012.03.020

来源: Elsevier

【 摘 要 】

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.)

【 授权许可】

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