title: Genome-wide prediction of childhood asthma and related phenotypes in a longitudinal birth cohort.
abstract: BACKGROUND
  Childhood wheezing and asthma vary greatly in clinical presentation and time course. The extent to which phenotypic variation reflects heterogeneity in disease pathways is unclear.
  
  
  OBJECTIVE
  We sought to assess the extent to which single nucleotide polymorphisms (SNPs) associated with childhood asthma in a genome-wide association study are predictive of asthma-related phenotypes.
  
  
  METHODS
  In 8365 children from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children, allelic scores were derived based on between 10 and 215,443 SNPs ranked according to the inverse of the P value for their association with physician-diagnosed asthma in an independent genome-wide association study (6176 cases and 7111 control subjects). We assessed the predictive value of allelic scores for asthma-related outcomes at age 7 to 9 years (physician's diagnosis, longitudinal wheezing phenotypes, and measurements of pulmonary function, bronchial responsiveness, and atopy).
  
  
  RESULTS
  Scores based on the 46 highest-ranked SNPs were associated with the symptom-based phenotypes early onset persistent wheeze (P< 10(-11); area under the receiver operating characteristic curve [AUC], 0.59) and intermediate-onset wheeze (P< 10(-3); AUC, 0.58). Among lower-ranked SNPs (ranks, 21,545-46,416), there was evidence for associations with diagnosed asthma (P< 10(-4); AUC, 0.54) and atopy (P< 10(-5); AUC, 0.55). We found little evidence of associations with transient early wheezing, reduced pulmonary function, or nonasthma phenotypes.
  
  
  CONCLUSIONS
  The genetic origins of asthma are diverse, and some pathways are specific to wheezing syndromes, whereas others are shared with atopy and bronchial hyperresponsiveness. Our study also provides evidence of etiologic differences among wheezing syndromes.
authors: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors: Ben D
authors: BD
authors: Spycher
authors: John
authors: J
authors: Henderson
authors: Raquel
authors: R
authors: Granell
authors: David M
authors: DM
authors: Evans
authors: George Davey
authors: GD
authors: Smith
authors: Nicholas J
authors: NJ
authors: Timpson
authors: Jonathan A C
authors: JA
authors: Sterne
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D001249:Asthma / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology*; D011237:Predictive Value of Tests; D011379:Prognosis; D012129:Respiratory Function Tests; D012135:Respiratory Sounds / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index