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

Klaus Bonnelykke, 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-MollerAngela Simpson, Beate St Pourcain, Lachlan Coin, Jennie Hui, Eugene H Walters, Carla M T Tiesler, David Duffy, Graham Jones, Guy B Marks, Patrick Danoy, Desiree Meszaros, Catherine Hayden, Anjali K Henders, Brett Chapman, Andrew J Kemp, Faang Cheah, Melissa C Southey, Mary Roberts, Euan R Tovey, Graham G Giles, Li P Chung, Paul S Thomas, Ian Feather, Suzanna Temple, John Beilby, Stephen Morrison, David P Johns, Chalermchai Mitrpant, Brad Shelton, Mark Jenkins, Warwick J Britton, Andrew S Kemp, Peter Le Souef, John L Hopper, Stephen R Leeder, Bill Musk, Nicholas G Martin, Matthew A Brown, Susan M Ring, Wendy L McArdle, Loren Price, Colin F Robertson, Juha Pekkanen, Clara 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 John Abramson, Benjamin P Fairfax, Julian C Knight, Ramneek Gupta, Philip J Thompson, Patrick Holt, Peter Sly, Joel N Hirschhorn, Mario Blekic, Stephan Weidinger, Hakon Hakonarsson, Kari Stefansson, Joachim Heinrich, Dirkje Postma, Adnan Custovic, Craig Pennell, Marjo-Riitta Jarvelin, Gerard H Koppelman, Nicholas Timpson, Manuel Ferreira, Hans Bisgaard, A John Henderson

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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 1 10,056 controls and followed up the top SNP at each of 26 loci in 6,11114 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
Number of pages5
JournalNature Genetics
Volume45
Issue number8
DOIs
Publication statusPublished - 2013

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