Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization.

TitleMeta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization.
Publication TypeJournal Article
Year of Publication2013
AuthorsBønnelykke K, Matheson MC, Pers TH, Granell R, Strachan DP, Alves A C, Linneberg A, Curtin JA, Warrington NM, Standl M, Kerkhof M, Jonsdottir I, Bukvic BK, Kaakinen M, Sleimann P, Thorleifsson G, Thorsteinsdottir U, Schramm K, Baltic S, Kreiner-Møller E, Simpson A, St Pourcain B, Coin L, Hui J, Walters EH, Tiesler CMT, Duffy DL, Jones G, Ring SM, McArdle WL, Price L, Robertson CF, Pekkanen J, Tang CS, Thiering E, Montgomery GW, Hartikainen A-L, Dharmage SC, Husemoen LL, Herder C, Kemp JP, Elliot P, James A, Waldenberger M, Abramson MJ, Fairfax BP, Knight JC, Gupta R, Thompson PJ, Holt P, Sly P, Hirschhorn JN, Blekic M, Weidinger S, Hakonarsson H, Stefansson K, Heinrich J, Postma DS, Custovic A, Pennell CE, Jarvelin M-R, Koppelman GH, Timpson N, Ferreira MA, Bisgaard H, Henderson JA
Corporate AuthorsAustralian Asthma Genetics Consortium(AAGC), EArly Genetics and Lifecourse Epidemiology(EAGLE) Consortium
JournalNat Genet
Volume45
Issue8
Pagination902-6
Date Published08/2013
ISSN1546-1718
KeywordsAlleles, Computational Biology, Gene Regulatory Networks, Genetic Loci, Genome-Wide Association Study, Genomics, Humans, Hypersensitivity, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Signal Transduction
Abstract

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.

DOI10.1038/ng.2694
Alternate JournalNat. Genet.
PubMed ID23817571