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

the 23andMe Research Team, AAGC collaborators

Research output: Contribution to journalLetter

6 Citations (Scopus)

Abstract

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries 1,2 . 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.

Original languageEnglish
Pages (from-to)1072-1080
Number of pages9
JournalNature Genetics
Volume50
Issue number8
DOIs
Publication statusPublished - 1 Aug 2018

Fingerprint

Genetic Loci
Genome
Genome-Wide Association Study
Rhinitis
Molecular Sequence Annotation
Allergens
Meta-Analysis
Hypersensitivity
Allergic Rhinitis
Antigens
Amino Acids
Incidence
Genes

Cite this

the 23andMe Research Team ; AAGC collaborators. / Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. In: Nature Genetics. 2018 ; Vol. 50, No. 8. pp. 1072-1080.
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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.

In: Nature Genetics, Vol. 50, No. 8, 01.08.2018, p. 1072-1080.

Research output: Contribution to journalLetter

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

AU - the 23andMe Research Team

AU - AAGC collaborators

AU - Waage, Johannes

AU - Standl, Marie

AU - Curtin, John A.

AU - Jessen, Leon E.

AU - Thorsen, Jonathan

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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

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AU - Jensen, Kamilla K.

AU - Jónsdóttir, Ingileif

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AU - Kaprio, Jaakko

AU - Kumar, Ashish

AU - Lee, Young Ae

AU - Levin, Albert M.

AU - Li, Xingnan

AU - Lorenzo-Diaz, Fabian

AU - Melén, Erik

AU - Mercader, Josep M.

AU - Meyers, Deborah A.

AU - Myers, Rachel

AU - Nicolae, Dan L.

AU - Nohr, Ellen A.

AU - Palviainen, Teemu

AU - Paternoster, Lavinia

AU - Pennell, Craig E.

AU - Pershagen, Göran

AU - Pino-Yanes, Maria

AU - Probst-Hensch, Nicole M.

AU - Rüschendorf, Franz

AU - Simpson, Angela

AU - Stefansson, Kari

AU - Sunyer, Jordi

AU - Sveinbjornsson, Gardar

AU - Thiering, Elisabeth

AU - Thompson, Philip J.

AU - Torrent, Maties

AU - Torrents, David

AU - Tung, Joyce Y.

AU - Wang, Carol A.

AU - Weidinger, Stephan

AU - Weiss, Scott

AU - Willemsen, Gonneke

AU - Williams, L. Keoki

AU - Ober, Carole

AU - Hinds, David A.

AU - Ferreira, Manuel A.

AU - Bisgaard, Hans

AU - Strachan, David P.

AU - Bønnelykke, Klaus

PY - 2018/8/1

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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 countries 1,2 . 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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JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

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