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

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

Research output: Contribution to journalArticle (Academic Journal)peer-review

159 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)902-906
JournalNature Genetics
Volume45
Issue number8
Early online date30 Jun 2013
DOIs
Publication statusPublished - Aug 2013

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