Examination of the relationship between variation at 17q21 and childhood wheeze phenotypes

The Journal of Allergy and Clinical Immunology
Raquel GranellJonathan A C Sterne

Abstract

Genome-wide association studies have identified associations of genetic variants at 17q21 near ORMDL3 with childhood asthma. We sought to determine whether associations in this region are specific to particular asthma phenotypes and specific to ORMDL3. We examined associations between 244 independent single nucleotide polymorphisms (SNPs) plus 13 previously identified asthma-related SNPs in the region between 34 and 36 Mb on chromosome 17 and early wheezing phenotypes, doctor-diagnosed asthma and atopy at 7½ years, and bronchial hyperresponsiveness and lung function at 8½ years in 7045 children from the Avon Longitudinal Study of Parents and Children birth cohort study. With this, cis expression quantitative trait loci signals for the same SNPs were assessed in 875 samples across genes in the same region. The strongest evidence for phenotypic association was seen for persistent wheezing (rs8076131 near ORMDL3: relative risk ratio [RRR], 1.60 [95% CI, 1.40-1.84], P = 1.4 × 10(-11); rs2305480 near GSDML: RRR, 1.60 [95% CI, 1.39-1.83], P = 1.5 × 10(-11); and rs9303277 near IKZF3: RRR, 1.57 [95% CI, 1.37-1.79], P = 4.4 × 10(-11)). Similar but less precisely estimated effects were seen for intermediate-onset wheeze, but there was li...Continue Reading

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Related Concepts

Genome-Wide Association Study
ORMDL3 gene
ORMDL3 protein, human
Dermatitis, Atopic
Granulocyte Colony-Stimulating Factor
RABL6 gene
Respiratory Physiology
ZPBP2 gene
Insulin Resistance
Gene Expression

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