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Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Item Type:Article
Title:Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis
Creators Name:Waage, J. and Standl, M. and Curtin, J.A. and Jessen, L.E. and Thorsen, J. and Tian, C. and Schoettler, N. and Flores, C. and Abdellaoui, A. and Ahluwalia, T.S. and Alves, A.C. and Amaral, A.F.S. and Antó, J.M. and Arnold, A. and Barreto-Luis, A. and Baurecht, H. and van Beijsterveldt, C.E.M. and Bleecker, E.R. and Bonàs-Guarch, S. and Boomsma, D.I. and Brix, S. and Bunyavanich, S. and Burchard, E.G. and Chen, Z. and Curjuric, I. and Custovic, A. and den Dekker, H.T. and Dharmage, S.C. and Dmitrieva, J. and Duijts, L. and Ege, M.J. and Gauderman, W.J. and Georges, M. and Gieger, C. and Gilliland, F. and Granell, R. and Gui, H. and Hansen, T. and Heinrich, J. and Henderson, J. and Hernandez-Pacheco, N. and Holt, P. and Imboden, M. and Jaddoe, V.W.V. and Jarvelin, M.R. and Jarvis, D.L. and Jensen, K.K. and Jónsdóttir, I. and Kabesch, M. and Kaprio, J. and Kumar, A. and Lee, Y.A. and Levin, A.M. and Li, X. and Lorenzo-Diaz, F. and Melén, E. and Mercader, J.M. and Meyers, D.A. and Myers, R. and Nicolae, D.L. and Nohr, E.A. and Palviainen, T. and Paternoster, L. and Pennell, C.E. and Pershagen, G. and Pino-Yanes, M. and Probst-Hensch, N.M. and Rüschendorf, F. and Simpson, A. and Stefansson, K. and Sunyer, J. and Sveinbjornsson, G. and Thiering, E. and Thompson, P.J. and Torrent, M. and Torrents, D. and Tung, J.Y. and Wang, C.A. and Weidinger, S. and Weiss, S. and Willemsen, G. and Williams, L.K. and Ober, C. and Hinds, D.A. and Ferreira, M.A. and Bisgaard, H. and Strachan, D.P. and Bønnelykke, K.
Abstract:Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.
Source:Nature Genetics
ISSN:1061-4036
Publisher:Nature Publishing Group (U.S.A.)
Volume:50
Number:8
Page Range:1072-1080
Date:August 2018
Additional Information:Erratum in: Nat Genet 50(9): 1343.
Official Publication:https://doi.org/10.1038/s41588-018-0157-1
PubMed:View item in PubMed

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