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

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.

• Authors: Johannes Waage, Marie Standl, John A Curtin, Leon E Jessen, Jonathan Thorsen, Chao Tian, Nathan Schoettler, 23andMe Research Team, AAGC collaborators, 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, 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, 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, L Keoki Williams, Carole Ober, David A Hinds, Manuel A Ferreira, Hans Bisgaard, David P Strachan, Klaus Bønnelykke
• Journal: Nature genetics (Nat Genet) Vol. 50 Issue 8 Pg. 1072-1080 (08 2018) ISSN: 1546-1718 [Electronic] United States
• PMID: 30013184 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• HLA Antigens

Topics

• 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