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

The 23andMe Research Team, AAGC collaborators

Publikation: Bidrag til tidsskriftLetterForskningpeer review

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Resumé

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.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind50
Udgave nummer8
Sider (fra-til)1072–1080
ISSN1061-4036
DOI
StatusUdgivet - aug. 2018

Fingeraftryk

Genome-Wide Association Study
Allergens
Meta-Analysis
Hypersensitivity
Amino Acids
Incidence

Citer dette

The 23andMe Research Team ; AAGC collaborators. / Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. I: Nature Genetics. 2018 ; Bind 50, Nr. 8. s. 1072–1080.
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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.",
author = "Johannes Waage and Marie Standl and Curtin, {John A.} and Jessen, {Leon E.} and Jonathan Thorsen and Chao Tian and Nathan Schoettler and Carlos Flores and Abdel Abdellaoui and Ahluwalia, {Tarunveer S.} and Alves, {Alexessander C.} and Amaral, {Andre F.S.} and Ant{\'o}, {Josep M.} and Andreas Arnold and Amalia Barreto-Luis and Hansj{\"o}rg Baurecht and {van Beijsterveldt}, {Catharina E.M.} and Bleecker, {Eugene R.} and S{\'i}lvia Bon{\`a}s-Guarch and Boomsma, {Dorret I.} and Susanne Brix and Supinda Bunyavanich and Burchard, {Esteban G.} and Zhanghua Chen and Ivan Curjuric and Adnan Custovic and {Den Dekker}, {Herman T.} and Dharmage, {Shyamali C.} and Julia Dmitrieva and Liesbeth Duijts and Ege, {Markus J.} and Gauderman, {W. James} and Michel Georges and Christian Gieger and Frank Gilliland and Raquel Granell and Hongsheng Gui and Torben Hansen and Joachim Heinrich and John Henderson and Natalia Hernandez-Pacheco and Patrick Holt and Medea Imboden and Jaddoe, {Vincent W.V.} and Jarvelin, {Marjo Riitta} and Jarvis, {Deborah L.} and Jensen, {Kamilla K.} and Ingileif J{\'o}nsd{\'o}ttir and Michael Kabesch and Nohr, {Ellen A.} and {The 23andMe Research Team} and {AAGC collaborators}",
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Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. / The 23andMe Research Team; AAGC collaborators.

I: Nature Genetics, Bind 50, Nr. 8, 08.2018, s. 1072–1080.

Publikation: Bidrag til tidsskriftLetterForskningpeer review

TY - JOUR

T1 - Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

AU - Waage, Johannes

AU - Standl, Marie

AU - Curtin, John A.

AU - Jessen, Leon E.

AU - Thorsen, Jonathan

AU - Tian, Chao

AU - Schoettler, Nathan

AU - Flores, Carlos

AU - Abdellaoui, Abdel

AU - Ahluwalia, Tarunveer S.

AU - Alves, Alexessander C.

AU - Amaral, Andre F.S.

AU - Antó, Josep M.

AU - Arnold, Andreas

AU - Barreto-Luis, Amalia

AU - Baurecht, Hansjörg

AU - van Beijsterveldt, Catharina E.M.

AU - Bleecker, Eugene R.

AU - Bonàs-Guarch, Sílvia

AU - Boomsma, Dorret I.

AU - Brix, Susanne

AU - Bunyavanich, Supinda

AU - Burchard, Esteban G.

AU - Chen, Zhanghua

AU - Curjuric, Ivan

AU - Custovic, Adnan

AU - Den Dekker, Herman T.

AU - Dharmage, Shyamali C.

AU - Dmitrieva, Julia

AU - Duijts, Liesbeth

AU - Ege, Markus J.

AU - Gauderman, W. James

AU - Georges, Michel

AU - Gieger, Christian

AU - Gilliland, Frank

AU - Granell, Raquel

AU - Gui, Hongsheng

AU - Hansen, Torben

AU - Heinrich, Joachim

AU - Henderson, John

AU - Hernandez-Pacheco, Natalia

AU - Holt, Patrick

AU - Imboden, Medea

AU - Jaddoe, Vincent W.V.

AU - Jarvelin, Marjo Riitta

AU - Jarvis, Deborah L.

AU - Jensen, Kamilla K.

AU - Jónsdóttir, Ingileif

AU - Kabesch, Michael

AU - Nohr, Ellen A.

AU - The 23andMe Research Team

AU - AAGC collaborators

PY - 2018/8

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N2 - 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.

AB - 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.

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EP - 1080

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

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