Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up the top SNP at each of 26 loci in 6,114 affected individuals and 9,920 controls. We increased the number of susceptibility loci with genome-wide significant association with allergic sensitization from three to ten, including SNPs in or near TLR6, C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2 and HLA-B. All the top SNPs were associated with allergic symptoms in an independent study. Risk-associated variants at these ten loci were estimated to account for at least 25% of allergic sensitization and allergic rhinitis. Understanding the molecular mechanisms underlying these associations may provide new insights into the etiology of allergic disease.
SUMMARY – A cross-sectional study was carried out in Brod-Posavina County, Croatia, to assess the prevalence of allergic diseases and atopy, as well as to investigate the possible etiologic factors for asthma, allergic rhinitis and eczema in childhood. The study included 1687 schoolchildren aged 10-11 years. Data were collected using standardized International Study of Asthma and Allergies in Childhood (ISAAC) Phase II written questionnaire. Skin prick tests were performed to provide an objective measure of atopy, defined as skin reactivity to one or more allergens. Lifetime prevalence of wheezing was 22.7%, rhinitis symptoms 22.5%, and eczema symptoms 17.9%. Period prevalence in the past 12 months was 7.9% for attacks of wheezing, 9.9% for rhinoconjunctivitis symptoms, and 10.1% for eczema symptoms. Of the children in which skin prick test was performed, 20.2% were positive for at least one of the allergens used, with house dust mite sensitization being the most frequent one. Risk factors for allergic disease include allergic disease in family, atopy, sensitization to indoor and outdoor allergens, and environmental tobacco smoke exposure at home. International comparison with the results of other ISAAC Phase II studies showed the Brod-Posavina County to be an area with moderate prevalence of atopy and current asthma symptoms.
We demonstrated several novel significant interactions between polymorphisms in 20p13-p12 and early-life ETS exposure with asthma presence and, amongst asthmatics, a significant association with the severity of their disease.
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