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

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

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. 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.

Allergens/genetics, Case-Control Studies, Genetic Loci/genetics, Genetic Predisposition to Disease/genetics, Genetic Variation/genetics, Genome, Human/genetics, Genome-Wide Association Study/methods, HLA Antigens/genetics, Humans, Phenotype, Rhinitis, Allergic/genetics, Risk
1061-4036
1072-1080
Waage, Johannes
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Standl, Marie
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Curtin, John A
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Jessen, Leon E
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Thorsen, Jonathan
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Tian, Chao
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Schoettler, Nathan
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Flores, Carlos
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Abdellaoui, Abdel
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Ahluwalia, Tarunveer S
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Couto Alves, Alex
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Amaral, Andre F S
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Antó, Josep M
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Baurecht, Hansjörg
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van Beijsterveldt, Catharina E M
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Bleecker, Eugene R
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Bonàs-Guarch, Sílvia
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Boomsma, Dorret I
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Brix, Susanne
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Bunyavanich, Supinda
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Burchard, Esteban G
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Chen, Zhanghua
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Curjuric, Ivan
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Custovic, Adnan
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den Dekker, Herman T
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Dharmage, Shyamali C
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Dmitrieva, Julia
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Duijts, Liesbeth
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Ege, Markus J
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Gauderman, W James
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Georges, Michel
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Gieger, Christian
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Gilliland, Frank
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Granell, Raquel
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Gui, Hongsheng
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Hansen, Torben
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Heinrich, Joachim
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Henderson, John
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Hernandez-Pacheco, Natalia
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Holt, Patrick
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Imboden, Medea
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Jaddoe, Vincent W V
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Jarvelin, Marjo-Riitta
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Jarvis, Deborah L
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Jensen, Kamilla K
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Jónsdóttir, Ingileif
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Kabesch, Michael
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Ferreira, Manuel A
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23andMe Research Team
Waage, Johannes
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Standl, Marie
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Curtin, John A
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Jessen, Leon E
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Thorsen, Jonathan
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Tian, Chao
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Schoettler, Nathan
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Flores, Carlos
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Abdellaoui, Abdel
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Ahluwalia, Tarunveer S
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Couto Alves, Alex
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Amaral, Andre F S
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Antó, Josep M
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Arnold, Andreas
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Barreto-Luis, Amalia
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Baurecht, Hansjörg
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van Beijsterveldt, Catharina E M
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Bleecker, Eugene R
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Bonàs-Guarch, Sílvia
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Boomsma, Dorret I
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Brix, Susanne
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Bunyavanich, Supinda
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Burchard, Esteban G
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Chen, Zhanghua
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Curjuric, Ivan
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Custovic, Adnan
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den Dekker, Herman T
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Dharmage, Shyamali C
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Dmitrieva, Julia
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Duijts, Liesbeth
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Ege, Markus J
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Gauderman, W James
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Georges, Michel
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Gieger, Christian
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Gilliland, Frank
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Granell, Raquel
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Gui, Hongsheng
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Hansen, Torben
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Heinrich, Joachim
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Henderson, John
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Hernandez-Pacheco, Natalia
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Holt, Patrick
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Imboden, Medea
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Jaddoe, Vincent W V
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Jarvelin, Marjo-Riitta
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Jarvis, Deborah L
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Jensen, Kamilla K
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Jónsdóttir, Ingileif
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Kabesch, Michael
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Ferreira, Manuel A
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23andMe Research Team (2018) Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. Nature Genetics, 50 (8), 1072-1080. (doi:10.1038/s41588-018-0157-1).

Record type: Article

Abstract

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. 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.

This record has no associated files available for download.

More information

Published date: August 2018
Keywords: Allergens/genetics, Case-Control Studies, Genetic Loci/genetics, Genetic Predisposition to Disease/genetics, Genetic Variation/genetics, Genome, Human/genetics, Genome-Wide Association Study/methods, HLA Antigens/genetics, Humans, Phenotype, Rhinitis, Allergic/genetics, Risk

Identifiers

Local EPrints ID: 494375
URI: http://eprints.soton.ac.uk/id/eprint/494375
DOI: doi:10.1038/s41588-018-0157-1
ISSN: 1061-4036
PURE UUID: acfb56ef-c0b7-4676-aea6-f94ca547d3de
ORCID for Alex Couto Alves: ORCID iD orcid.org/0000-0001-8519-7356
ORCID for Manuel A Ferreira: ORCID iD orcid.org/0000-0002-2428-0284

Catalogue record

Date deposited: 07 Oct 2024 16:40
Last modified: 08 Oct 2024 02:13

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Contributors

Author: Johannes Waage
Author: Marie Standl
Author: John A Curtin
Author: Leon E Jessen
Author: Jonathan Thorsen
Author: Chao Tian
Author: Nathan Schoettler
Author: Carlos Flores
Author: Abdel Abdellaoui
Author: Tarunveer S Ahluwalia
Author: Alex Couto Alves ORCID iD
Author: Andre F S Amaral
Author: Josep M Antó
Author: Andreas Arnold
Author: Amalia Barreto-Luis
Author: Hansjörg Baurecht
Author: Catharina E M van Beijsterveldt
Author: Eugene R Bleecker
Author: Sílvia Bonàs-Guarch
Author: Dorret I Boomsma
Author: Susanne Brix
Author: Supinda Bunyavanich
Author: Esteban G Burchard
Author: Zhanghua Chen
Author: Ivan Curjuric
Author: Adnan Custovic
Author: Herman T den Dekker
Author: Shyamali C Dharmage
Author: Julia Dmitrieva
Author: Liesbeth Duijts
Author: Markus J Ege
Author: W James Gauderman
Author: Michel Georges
Author: Christian Gieger
Author: Frank Gilliland
Author: Raquel Granell
Author: Hongsheng Gui
Author: Torben Hansen
Author: Joachim Heinrich
Author: John Henderson
Author: Natalia Hernandez-Pacheco
Author: Patrick Holt
Author: Medea Imboden
Author: Vincent W V Jaddoe
Author: Marjo-Riitta Jarvelin
Author: Deborah L Jarvis
Author: Kamilla K Jensen
Author: Ingileif Jónsdóttir
Author: Michael Kabesch
Author: Manuel A Ferreira ORCID iD
Corporate Author: 23andMe Research Team

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