Genome-wide prediction of childhood asthma and related phenotypes in a longitudinal birth cohort

Spycher, Ben D., Henderson, John, Granell, Raquel, Evans, David M., Smith, George Davey, Timpson, Nicholas J. and Sterne, Jonathan A. C. (2012) Genome-wide prediction of childhood asthma and related phenotypes in a longitudinal birth cohort. Journal of Allergy and Clinical Immunology, 130 2: 503-509.e7. doi:10.1016/j.jaci.2012.06.002


Author Spycher, Ben D.
Henderson, John
Granell, Raquel
Evans, David M.
Smith, George Davey
Timpson, Nicholas J.
Sterne, Jonathan A. C.
Title Genome-wide prediction of childhood asthma and related phenotypes in a longitudinal birth cohort
Journal name Journal of Allergy and Clinical Immunology   Check publisher's open access policy
ISSN 0091-6749
1097-6825
Publication date 2012-01-01
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.jaci.2012.06.002
Open Access Status Not yet assessed
Volume 130
Issue 2
Start page 503
End page 509.e7
Total pages 14
Place of publication Philadelphia, PA, United States
Publisher Mosby
Language eng
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.
Formatted 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.

Conclusion: 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.
Keyword Forecasting
Genome-wide association study
Hypersensitivity
Respiratory function tests
Respiratory sounds
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 092731
MC 1614-2010
PCOFUND-GA-2008-229571
0401540
018996
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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