Bønnelykke, Klaus3; Matheson, Melanie C3; Pers, Tune Hannes1; Granell, Raquel3; Strachan, David P3; Alves, Alexessander Couto3; Linneberg, Allan René3; Curtin, John A3; Warrington, Nicole M3; Standl, Marie3; Kerkhof, Marjan3; Jonsdottir, Ingileif3; Bukvic, Blazenka K3; Kaakinen, Marika3; Sleimann, Patrick3; Thorleifsson, Gudmar3; Thorsteinsdottir, Unnur3; Schramm, Katharina3; Baltic, Svetlana3; Kreiner-Møller, Eskil3; Simpson, Angela3; Pourcain, Beate St3; Coin, Lachlan3; Hui, Jennie3; Walters, Eugene H3; Tiesler, Carla M T3; Duffy, David L3; Jones, Graham3; Ring, Susan M3; McArdle, Wendy L3; Price, Loren3; Robertson, Colin F3; Pekkanen, Juha3; Tang, Clara S3; Thiering, Elisabeth3; Montgomery, Grant W3; Hartikainen, Anna-Liisa3; Dharmage, Shyamali C3; Husemoen, Lise Lotte Nystrup3; Herder, Christian3; Kemp, John P3; Elliot, Paul3; James, Alan3; Waldenberger, Melanie3; Abramson, Michael J3; Fairfax, Benjamin P3; Knight, Julian C3; Gupta, Ramneek1; Thompson, Philip J3; Holt, Patrick3; Sly, Peter3; Hirschhorn, Joel N3; Blekic, Mario3; Weidinger, Stephan3; Hakonarsson, Hakon3; Stefansson, Kari3; Heinrich, Joachim3; Postma, Dirkje S3; Custovic, Adnan3; Pennell, Craig E3; Jarvelin, Marjo-Riitta3; Koppelman, Gerard H3; Timpson, Nicholas3; Ferreira, Manuel A3; Bisgaard, Hans3; Henderson, A John3
1 Department of Systems Biology, Technical University of Denmark2 Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark3 unknown
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.