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

Autori
Bønnelykke K, Matheson MC, Pers TH, Granell R, Strachan DP, Alves AC, 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 CM, Duffy DL, Jones G, Ring SM, McArdle WL, Price L, Robertson CF, Pekkanen J, Tang CS, Thiering E, Montgomery GW, Hartikainen AL, 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 MR, Koppelman GH, Timpson N, Ferreira MA, Bisgaard H, Henderson AJ

Izvornik
Nature genetics (1061-4036) 45 (2013), 8; 902-6

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Alleles Computational Biology Gene Regulatory Networks Genetic Loci* Genome-Wide Association Study* Genomics Humans Hypersensitivity/genetics* Hypersensitivity/metabolism Phenotype Polymorphism, Single Nucleotide Quantitative Trait Loci Signal Transduction

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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