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

TitleGenome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.
Publication TypeJournal Article
Year of Publication2018
AuthorsWaage J, Standl M, Curtin JA, Jessen LE, Thorsen J, Tian C, Schoettler N, Flores C, Abdellaoui A, Ahluwalia TS, Alves AC, Amaral AFS, Antó JM, Arnold A, Barreto-Luis A, Baurecht H, van Beijsterveldt CEM, Bleecker ER, Bonàs-Guarch S, Boomsma DI, Brix S, Bunyavanich S, Burchard EG, Chen Z, Curjuric I, Custovic A, Dekker HT den, Dharmage SC, Dmitrieva J, Duijts L, Ege MJ, Gauderman JW, Georges M, Gieger C, Gilliland F, Granell R, Gui H, Hansen T, Heinrich J, Henderson J, Hernandez-Pacheco N, Holt P, Imboden M, Jaddoe VWV, Jarvelin M-R, Jarvis DL, Jensen KK, Jonsdottir I, Kabesch M, Kaprio J, Kumar A, Lee Y-A, Levin AM, Li X, Lorenzo-Diaz F, Melén E, Mercader JM, Meyers DA, Myers R, Nicolae DL, Nohr EA, Palviainen T, Paternoster L, Pennell CE, Pershagen G, Pino-Yanes M, Probst-Hensch NM, Rüschendorf F, Simpson A, Stefansson K, Sunyer J, Sveinbjornsson G, Thiering E, Thompson PJ, Torrent M, Torrents D, Tung JY, Wang CA, Weidinger S, Weiss S, Willemsen G, L Williams K, Ober C, Hinds DA, Ferreira MA, Bisgaard H, Strachan DP, Bønnelykke K
Corporate Authors23andMe Research Team, AAGC collaborators
JournalNat Genet
Volume50
Issue8
Pagination1072-1080
Date Published2018 Aug
ISSN1546-1718
Abstract

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

DOI10.1038/s41588-018-0157-1
Alternate JournalNat. Genet.
PubMed ID30013184