University of Oulu

Waage, J.et al. (2018) Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis. Nature Genetics, 50 (8), 1072-1080. doi:10.1038/s41588-018-0157-1. Correction available online at https://doi.org/10.1038/s41588-018-0197-6

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

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Author: Waage, Johannes1; Standl, Marie2; Curtin, John A.3;
Jessen, Leon E.1; Thorsen, Jonathan1; Tian, Chao4; Schoettler, Nathan5; Flores, Carlos6,7; Abdellaoui, Abdel8,9; Ahluwalia, Tarunveer S.1; Alves, Alexessander C.10; Amaral, Andre F. S.11; Anto, Josep M.12,13,14,15; Arnold, Andreas16; Barreto-Luis, Amalia6; Baurecht, Hansjoerg17; van Beijsterveldt, Catharina E. M.8; Bleecker, Eugene R.18; Bonas-Guarch, Silvia19; Boomsman, Dorret I.8,20; Brix, Susanne8; Bunyavanich, Supinda18; Burchard, Esteban G.21,22; Chen, Zhanghua17; Curjuric, Ivan23,24; Custovic, Adnan25; den Dekker, Herman T.26,27,28; Dharmage, Shyamali C.29; Dmitrieva, Julia30; Duijts, Liesbeth26,28,31; Ege, Markus J.32,33; Gauderman, W. James34; Georges, Michel30; Gieger, Christian35; Gilliland, Frank34; Granell, Raquel36; Gui, Hongsheng37; Hansen, Torben38; Heinrich, Joachim39; Henderson, John36; Hernandez-Pacheco, Natalia40; Holt, Patrick41; Imboden, Medea23,24; Jaddoe, Vincent W. V.26,27,42; Järvelin, Marjo-Riitta10,43,44,45; Jarvis, Deborah L.11; Jensen, Kamilla K.46; Jonsdottir, Ingileif47,48; Kabesch, Michael49; Kaprio, Jaakko50,51,52; Kumar, Ashish23,24,53; Lee, Young-Ae54,55; Levin, Albert M.56; Li, Xingnan56,57; Lorenzo-Diaz, Fabian; Melen, Erik58; Mercader, Josep M.19,59,60,61,62; Meyers, Deborah A.; Myers, Rachel5; Nicolae, Dan L.5; Nohr, Ellen A.63; Palviainen, Teemu51; Paternoster, Lavinia36; Pennell, Craig E.64; Pershagen, Goran53,65; Pino-Yanes, Maria6,7,40; Probst-Hensch, Nicole M.; Ruschendorf, Franz; Simpson, Angela3; Stefansson, Kari47,48; Sunyer, Jordi12; Sveinbjornsson, Gardar; Thiering, Elisabeth2,66; Thompson, Philip J.67; Torrent, Maties68; Torrents, David19,69; Tung, Joyce Y.4; Wang, Carol A.64; Weidinger, Stephan17; Weiss, Scott70,71; Willemsen, Gonneke8; Williams, L. Keoki72; Ober, Carole5; Hinds, David A.4; Ferreira, Manuel A.73; Bisgaard, Hans1; Strachan, David P.74; Bonnelykke, Klaus1
Organizations: 1Univ Copenhagen, Herlev & Gentofte Hosp, COPSAC, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark.
2Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, Neuherberg, Germany.
3Univ Manchester, Div Infect Immun & Resp Med, Manchester Acad Hlth Sci Ctr, Manchester Univ NHS Fdn Trust, Manchester, Lancs, England.
423&Me Inc, Mountain View, CA USA.
5Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
6Univ La Laguna, Hosp Univ NS Candelaria, Res Unit, Tenerife, Spain.
7Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain.
8Vrije Univ Amsterdam, Dept Biol Psychol, Netherlands Twin Register, Amsterdam, Netherlands.
9Univ Amsterdam, Acad Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
10Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England.
11Imperial Coll London, Natl Heart & Lung Inst, Populat Hlth & Occupat Dis, London, England.
12ISGlobal, Barcelona, Spain.
13Hosp del Mar, Med Res Inst, IMIM, Barcelona, Spain.
14UPF, Barcelona, Spain.
15CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
16Univ Med Greifswald, Clin & Polyclin Dermatol, Greifswald, Germany.
17Univ Hosp Schleswig Hostein, Dept Dermatol Venereol & Allergol, Campus Kiel, Kiel, Germany.
18Univ Arizona, Coll Med, Dept Med, Div Pharmacogen & Genet Genom & Precis Med, Tucson, AZ USA.
19Joint BSC CRG IRB Res, BSC, Barcelona, Spain.
20APH, Amsterdam, Netherlands.
21Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
22Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
23Univ Basel, Basel, Switzerland.
24Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
25Imperial Coll London, Dept Pediat, London, England.
26Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.
27Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
28Erasmus MC, Div Resp Med, Dept Pediat, Rotterdam, Netherlands.
29Univ Melbourne, Melbourne Sch Populat & Global Hlth, Allergy & Lung Hlth Unit, Melbourne, Vic, Australia.
30Univ Liege, GIGA Inst, Unit Med Genom, Lab Anim Genom, Liege, Belgium.
31Erasmus MC, Div Neonatol, Dept Pediat, Rotterdam, Netherlands.
32Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Munich, Germany.
33German Ctr Lung Res DZL, Munich, Germany.
34Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
35Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.
36Univ Bristol, Bristol Med Sch, Populat Hlth Sci, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
37Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA.
38Univ Copenhagen, Sect Metab Genet, Dept Hlth & Med Sci, Novo Nordisk Fdn,Ctr Basic Metab Res, Copenhagen, Denmark.
39Univ Munich, Ludwig Maximilians Univ Munchen, Med Ctr, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany.
40Univ La Laguna, Dept Biochem Microbiol Cell Biol & Genet, Genom & Hlth Grp, Tenerife, Spain.
41TKI, Perth, WA, Australia.
42Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
43Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu, Finland.
44Univ Oulu, Bioctr Oulu, Oulu, Finland.
45Oulu Univ Hosp, Unit Primary Care, Oulu, Finland.
46Tech Univ Denmark, Dept Bio & Hlth Informat, Lyngby, Denmark.
47Amgen Inc, DeCODE Genet, Reykjavik, Iceland.
48Univ Iceland, Fac Med, Reykjavik, Iceland.
49Univ Childrens Hosp Regensburg KUNO, Dept Pediat Pneumol & Allergy, Regensburg, Germany.
50Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
51Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
52Natl Inst Hlth & Welf, Helsinki, Finland.
53Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
54MDC Mol Med, Berlin, Germany.
55Charite, Pediat Allergy Expt & Clin Res Ctr, Berlin, Germany.
56Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA.
57Univ Arizona, Coll Med, Dept Med, Div Genet Genom & Precis Med, Tucson, AZ USA.
58Sachs Childrens Hosp, Stockholm, Sweden.
59Broad Inst Harvard, Programs Metab & Med & Populat Genet, Cambridge, MA USA.
60MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
61Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
62Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
63Univ Southern Denmark, Odense Univ Hosp, Dept Obstet & Gynecol, 63Institute Clin Res, Odense, Denmark.
64Univ Newcastle, Fac Med & Hlth, Sch Med & Publ Hlth, Callaghan, NSW, Australia.
65Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden.
66Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Div Metab Dis & Nutrit Med, Munich, Germany.
67Univ Western Australia, Harry Perkins Inst Med Res, Inst Resp Hlth, Nedlands, WA, Australia.
68Inst Invest Sanitaria Illes Balears IdISBa, Ib Salut, Area Salut Menorca, Palma de Mallorca, Spain.
69ICREA, Barcelona, Spain.
70Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
71Harvard Med Sch, Boston, MA USA.
72Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI USA.
73QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
74St Georges Univ London, Populat Hlth Res Inst, London, England.
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019050714655
Language: English
Published: Springer Nature, 2018
Publish Date: 2019-05-07
Description:

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.

An Author Correction to this article was published on 16 August 2018. https://www.nature.com/articles/s41588-018-0197-6

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Series: Nature genetics
ISSN: 1061-4036
ISSN-E: 1546-1718
ISSN-L: 1061-4036
Volume: 50
Pages: 1072 - 1080
DOI: 10.1038/s41588-018-0157-1
OADOI: https://oadoi.org/10.1038/s41588-018-0157-1
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
Subjects:
Funding: The NFBC resource has been supported by grants from the Academy of Finland (project grants 104781, 120315, 129269, 1114194, 24300796, Center of Excellence in Complex Disease Genetics and SALVE), University Hospital Oulu, Biocenter, University of Oulu, Finland (75617), NHLBI grant 5R01HL087679-02 (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), ENGAGE project and grant agreement HEALTH-F4-2007-201413, EU FP7 EurHEALTHAgeing -277849, the Medical Research Council, UK (G0500539, G0600705, G1002319, PrevMetSyn/SALVE) and the MRC, Centenary Early Career Award. H2020 DynaHEALTH (European Union’s Horizon 2020 research and innovation programme under grant agreement No 633595); Exposomic, Genomic and Epigenomic Approach to Prediction of Metabolic and Cardiorespiratory function and Ill-Health (EGEA), Academy of Finland, Grant No 285547; ALEC Study (funded by the European Union's Horizon 2020 Research and Innovation programme under grant agreement No. 633212); H2020 / Marie Skłodowska-Curie Actions, CAPICE (Marie Curie Grant agreement Number 721567); National Public Health Institute, Biomedicum Helsinki, Finland.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(277849) EURHEALTHAGEING - European ResearcH on DevElopmentAL, BirtH and Genetic Determinants of Ageing
Academy of Finland Grant Number: 285547
Detailed Information: 285547 (Academy of Finland Funding decision)
Copyright information: © 2018, Springer Nature. This is a post-peer-review, pre-copyedit version of an article published in Nature Genetics. The final authenticated version is available online at: http://dx.doi.org/10.1038/s41588-018-0157-1.