Title

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

Authors

Johannes Waage
Marie Standl
John A Curtin
Leon E Jessen
Jonathan Thorsen
Chao Tian
Nathan Schoettler
Carlos Flores
Abdel Abdellaoui
Tarunveer S Ahluwalia
Alexessander C Alves
Andre F S Amaral
Josep M Antó
Andreas Arnold
Amalia Barreto-Luis
Hansjörg Baurecht
Catharina E M van Beijsterveldt
Eugene R Bleecker
Sílvia Bonàs-Guarch
Dorret I Boomsma
Susanne Brix
Supinda Bunyavanich
Esteban G Burchard
Zhanghua Chen
Ivan Curjuric
Adnan Custovic
Herman T den Dekker
Shyamali C Dharmage
Julia Dmitrieva
Liesbeth Duijts
Markus J Ege
W James Gauderman
Michel Georges
Christian Gieger
Frank Gilliland
Raquel Granell
Hongsheng Gui, Henry Ford Health SystemFollow
Torben Hansen
Joachim Heinrich
John Henderson
Natalia Hernandez-Pacheco
Patrick Holt
Medea Imboden
Vincent W V Jaddoe
Marjo-Riitta Jarvelin
Deborah L Jarvis
Kamilla K Jensen
Ingileif Jónsdóttir
Michael Kabesch
Jaakko Kaprio
Ashish Kumar
Young-Ae Lee
Albert M. Levin, Henry Ford Health SystemFollow
Xingnan Li
Fabian Lorenzo-Diaz
Erik Melén
Josep M Mercader
Deborah A Meyers
Rachel Myers
Dan L Nicolae
Ellen A Nohr
Teemu Palviainen
Lavinia Paternoster
Craig E Pennell
Göran Pershagen
Maria Pino-Yanes
Nicole M Probst-Hensch
Franz Rüschendorf
Angela Simpson
Kari Stefansson
Jordi Sunyer
Gardar Sveinbjornsson
Elisabeth Thiering
Philip J Thompson
Maties Torrent
David Torrents
Joyce Y Tung
Carol A Wang
Stephan Weidinger
Scott Weiss
Gonneke Willemsen
Keoki L. Williams, Henry Ford Health SystemFollow
Carole Ober
David A Hinds
Manuel A Ferreira
Hans Bisgaard
David P Strachan
Klaus Bønnelykke

Document Type

Article

Publication Date

8-1-2018

Publication Title

Nature genetics

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.

Medical Subject Headings

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

PubMed ID

30013184

Volume

50

Issue

8

First Page

1072

Last Page

1080

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