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

Klaus Bønnelykke, Melanie C. Matheson, Tune H. Pers, Raquel Granell, David P. Strachan, Alexessander Couto Alves, Allan Linneberg, John A. Curtin, Nicole M. Warrington, Marie Standl, Marjan Kerkhof, Ingileif Jonsdottir, Blazenka K. Bukvic, Marika Kaakinen, Patrick Sleimann, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Katharina Schramm, Svetlana Baltic, Eskil Kreiner MøllerAngela Simpson, Beate St Pourcain, Lachlan Coin, Jennie Hui, Eugene H. Walters, Carla M T Tiesler, David L. Duffy, Graham Jones, Susan M. Ring, Wendy L. McArdle, Loren Price, Colin F. Robertson, Juha Pekkanen, Clara S. Tang, Elisabeth Thiering, Grant W. Montgomery, Anna Liisa Hartikainen, Shyamali C. Dharmage, Lise L. Husemoen, Christian Herder, John P. Kemp, Paul Elliot, Alan James, Melanie Waldenberger, Michael J. Abramson, Benjamin P. Fairfax, C. Julian Knight, Ramneek Gupta, Philip J. Thompson, Patrick Holt, Peter Sly, Joel N. Hirschhorn, Mario Blekic, Stephan Weidinger, Hakon Hakonarsson, Kari Stefansson, Joachim Heinrich, Dirkje S. Postma, Adnan Custovic, Craig E. Pennell, Marjo Riitta Jarvelin, Gerard H. Koppelman, Nicholas Timpson, Manuel A. Ferreira, Hans Bisgaard, A. John Henderson

    Research output: Contribution to journalArticlepeer-review

    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. © 2013 Nature America, Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)902-906
    Number of pages4
    JournalNature Genetics
    Volume45
    Issue number8
    DOIs
    Publication statusPublished - Aug 2013

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