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


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.

SUBMITTER: Bonnelykke K 

PROVIDER: S-EPMC4922420 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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

Bønnelykke Klaus K   Matheson Melanie C MC   Pers Tune H TH   Granell Raquel R   Strachan David P DP   Alves Alexessander Couto AC   Linneberg Allan A   Curtin John A JA   Warrington Nicole M NM   Standl Marie M   Kerkhof Marjan M   Jonsdottir Ingileif I   Bukvic Blazenka K BK   Kaakinen Marika M   Sleimann Patrick P   Thorleifsson Gudmar G   Thorsteinsdottir Unnur U   Schramm Katharina K   Baltic Svetlana S   Kreiner-Møller Eskil E   Simpson Angela A   St Pourcain Beate B   Coin Lachlan L   Hui Jennie J   Walters Eugene H EH   Tiesler Carla M T CMT   Duffy David L DL   Jones Graham G   Ring Susan M SM   McArdle Wendy L WL   Price Loren L   Robertson Colin F CF   Pekkanen Juha J   Pekkanen Juha J   Tang Clara S CS   Thiering Elisabeth E   Montgomery Grant W GW   Hartikainen Anna-Liisa AL   Dharmage Shyamali C SC   Husemoen Lise L LL   Herder Christian C   Kemp John P JP   Elliot Paul P   James Alan A   Waldenberger Melanie M   Abramson Michael J MJ   Fairfax Benjamin P BP   Knight Julian C JC   Knight Julian C JC   Gupta Ramneek R   Thompson Philip J PJ   Holt Patrick P   Sly Peter P   Hirschhorn Joel N JN   Blekic Mario M   Weidinger Stephan S   Hakonarsson Hakon H   Stefansson Kari K   Heinrich Joachim J   Postma Dirkje S DS   Custovic Adnan A   Pennell Craig E CE   Pennell Craig E CE   Jarvelin Marjo-Riitta MR   Koppelman Gerard H GH   Timpson Nicholas N   Ferreira Manuel A MA   Ferreira Manuel A MA   Bisgaard Hans H   Henderson A John AJ  

Nature genetics 20130630 8


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 thr  ...[more]

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