Mechanisms of allergy and clinical immunologyGenome-wide prediction of childhood asthma and related phenotypes in a longitudinal birth cohort
Section snippets
Methods
More detail is provided in the Methods section of this article’s Online Repository at www.jacionline.org.
Results
Genetic data were available for 8365 unrelated white European ALSPAC children. Of these, 5748 (68.7%) replied to the questionnaire at age 7 years, and 6128 (73.3%) and 5621 (67.2%) participated in study clinics at ages 7 to 8 and 8 to 9 years, respectively. Wheezing phenotypes based on repeated assessment of current wheeze throughout the first 7 years of life3 were available in 7176 (85.8%) children. Of these, 506 (7.1%) had persistent, 338 (4.7%) had late-onset, 168 (2.3%) had
Main findings
We used SNPs associated with asthma in the GABRIEL GWAS16 to construct genome-wide prediction scores and evaluated their performance in an independent population-based birth cohort study. Prediction scores were most strongly associated with the persistent and intermediate-onset wheezing phenotypes, which were defined previously by using latent class analysis.3 We found associations with asthma among the lower-ranked SNPs with P values for association that did not reach genome-wide thresholds in
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The UK Medical Research Council and the Wellcome Trust (grant reference 092731) and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children. B.D.S. is the recipient of a European Respiratory Society/Marie Curie Joint Research Fellowship (no. MC 1614-2010). The research leading to these results has received funding from the European Respiratory Society and the European Community’s Seventh Framework Programme FP7/2007-2013–Marie Curie Actions under grant agreement RESPIRE, PCOFUND-GA-2008-229571. R.G. was supported by the UK Medical Research Council (grant no. 0401540). The GABRIEL project was supported by a contract from the European Commission (018996) and grants from the French Ministry of Research, the Wellcome Trust (WT084703MA), and Asthma UK.
Disclosure of potential conflict of interest: J. Henderson, G. D. Smith, and J. A. C. Sterne receive research support from the Medical Research Council and the Wellcome Trust. R. Granell receives research support from the Medical Research Council. The rest of the authors declare that they have no relevant conflicts of interest.