title: Genome-wide association study of the age of onset of childhood asthma.
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.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Erick
authors.initials: E
authors.lastname: Forno
authors.forename: Jessica
authors.initials: J
authors.lastname: Lasky-Su
authors.forename: Blanca
authors.initials: B
authors.lastname: Himes
authors.forename: Judie
authors.initials: J
authors.lastname: Howrylak
authors.forename: Clare
authors.initials: C
authors.lastname: Ramsey
authors.forename: John
authors.initials: J
authors.lastname: Brehm
authors.forename: Barbara
authors.initials: B
authors.lastname: Klanderman
authors.forename: John
authors.initials: J
authors.lastname: Ziniti
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
authors.forename: Goran
authors.initials: G
authors.lastname: Pershagen
authors.forename: Magnus
authors.initials: M
authors.lastname: Wickman
authors.forename: Fernando
authors.initials: F
authors.lastname: Martinez
authors.forename: Dave
authors.initials: D
authors.lastname: Mauger
authors.forename: Christine
authors.initials: C
authors.lastname: Sorkness
authors.forename: Kelan
authors.initials: K
authors.lastname: Tantisira
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Raby
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.forename: Juan C
authors.initials: JC
authors.lastname: Celedón
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001249:Asthma / Q000453:epidemiology* / Q000235:genetics; D002648:Child; D015331:Cohort Studies; D003364:Costa Rica / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009656:North America / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology