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

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Title: Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis
Authors: Waage, J
Standl, M
Curtin, JA
Jessen, L
Thorsen, J
The 23andMe Research Team
AAGC Collaborators
Abdellaoui, A
Ahluwalia, TS
Alves, A
Amaral, AFS
Anto, JM
Arnold, A
Flores, C
Baurecht, H
Beijstervedldt, TCEM
Bleecker, ER
Bonas-Guarch, S
Boomsma, D
Brix, S
Bunyavanich, S
Burchard, E
Chen, Z
Curjuric, I
Custovic, A
Den Dekker, M
Dharmage, SC
Dmitrieva, J
Duijts, L
Ege, M
Barreto-Luis, A
Gauderman, WJ
Georges, M
Gieger, C
Gilliland, F
Granell, R
Gui, H
Hansen, T
Heinrich, J
Henderson, J
Hernandez-Pacheco, N
Hinds, DA
Holt, P
Imboden, M
Jaddoe, V
Jarvelin, M
Jarvis, D
Jensen, KK
Jonsdottir, I
Kabesch, M
Kaprio, J
Kumar, A
Lee, Y
Levin, AM
Li, X
Lorenz-Diaz, F
Melen, E
Mercader, JM
Meyers, DA
Nicolae, DL
Nohr, E
Palvianinen, T
Paternoster, L
Pennell, C
Pershagen, G
Pino-Yanes, M
Probst-Hensch, NM
Ruschendorf, F
Schoettler, N
Simpson, A
Stefansson, K
Sunyer, J
Sveinbjornsson, G
Thiering, E
Thompson, PJ
Tian, C
Torrent, M
Torrents, D
Tung, JY
Wang, C
Weidinger, S
Weiss, S
Willemsen, G
Williams, LK
Ober, C
Ferreira, MA
Bisgaard, H
Strachan, D
Bonnelykke, K
Item Type: Journal Article
Abstract: Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, and with increasing incidence in westernized countries.1,2 To elucidate the genetic architecture and understand disease mechanisms of allergic rhinitis, 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 implied genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants of importance for antigen binding. We further performed GWASs of allergic sensitization against inhalant allergens and non-allergic rhinitis suggesting 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.
Issue Date: Aug-2018
Date of Acceptance: 10-May-2018
URI: http://hdl.handle.net/10044/1/60029
DOI: https://doi.org/10.1038/s41588-018-0157-1
ISSN: 1061-4036
Publisher: Nature Publishing Group
Start Page: 1072
End Page: 1080
Journal / Book Title: Nature Genetics
Volume: 50
Copyright Statement: © 2018 Nature Research. The final publication is available at Springer via https://doi.org/10.1038/s41588-018-0157-1
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
HAY-FEVER
CELL DEVELOPMENT
DENDRITIC CELLS
EXPRESSION
VARIANTS
ASTHMA
RECEPTOR
HERITABILITY
METAANALYSIS
DISEASES
Allergens
Case-Control Studies
Genetic Loci
Genetic Predisposition to Disease
Genetic Variation
Genome, Human
Genome-Wide Association Study
HLA Antigens
Humans
Phenotype
Rhinitis, Allergic
Risk
23andMe Research Team
AAGC collaborators
Humans
Genetic Predisposition to Disease
Allergens
HLA Antigens
Risk
Case-Control Studies
Phenotype
Genome, Human
Genetic Variation
Genome-Wide Association Study
Genetic Loci
Rhinitis, Allergic
Developmental Biology
11 Medical and Health Sciences
06 Biological Sciences
Publication Status: Published
Online Publication Date: 2018-07-16
Appears in Collections:Infectious Disease Epidemiology
National Heart and Lung Institute
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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