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Nat Genet. 2018 Aug;50(8):1072-1080. doi: 10.1038/s41588-018-0157-1. Epub 2018 Jul 16.

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

Author information

1
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
2
Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
3
Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.
4
23andMe, Inc., Mountain View, CA, USA.
5
Department of Human Genetics, University of Chicago, Chicago, IL, USA.
6
Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Tenerife, Spain.
7
CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
8
Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
9
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
10
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK.
11
Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College London, London, UK.
12
ISGlobal, Barcelona, Spain.
13
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
14
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
15
CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
16
Clinic and Polyclinic of Dermatology, University Medicine Greifswald, Greifswald, Germany.
17
Department of Dermatology, Venereology and Allergology, University-Hospital Schleswig-Hostein, Campus Kiel, Kiel, Germany.
18
Divisions of Pharmacogenomics and Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA.
19
Barcelona Supercomputing Center (BSC), Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona, Spain.
20
APH Amsterdam Public Health, Amsterdam, The Netherlands.
21
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
22
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
23
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
24
Department of Bioengineering & Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
25
Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
26
University of Basel, Basel, Switzerland.
27
Swiss Tropical and Public Health Institute, Basel, Switzerland.
28
Department of Paediatrics, Imperial College London, London, UK.
29
The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
30
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
31
Department of Pediatrics, Division of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
32
Allergy and Lung Health Unit, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
33
Laboratory of Animal Genomics, Unit of Medical Genomics, GIGA Institute, University of Liège, Liège, Belgium.
34
Department of Pediatrics, Division of Neonatology, Erasmus Medical Center, Rotterdam, The Netherlands.
35
LMU Munich, Dr von Hauner Children's Hospital, Munich, and German Center for Lung Research (DZL), Munich, Germany.
36
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
37
MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
38
Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA.
39
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
40
Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University of Munich Medical Center, Ludwig-Maximilians-Universität München, Munich, Germany.
41
Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, La Laguna, Tenerife, Spain.
42
Telethon Kids Institute (TKI), Perth, Western Australia, Australia.
43
Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.
44
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
45
Biocenter Oulu, University of Oulu, Oulu, Finland.
46
Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
47
Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark.
48
deCODE genetics/Amgen Inc, Reykjavik, Iceland.
49
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
50
Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.
51
Department of Public Health, University of Helsinki, Helsinki, Finland.
52
Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
53
National Institute for Health and Welfare, Helsinki, Finland.
54
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
55
Max-Delbrück-Center (MDC) for Molecular Medicine, Berlin, Germany.
56
Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany.
57
Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
58
Divisions of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA.
59
Sachs' Children's Hospital, Stockholm, Sweden.
60
Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
61
Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
62
Institute of Clinical Research, University of Southern Denmark, Department of Obstetrics & Gynecology, Odense University Hospital, Odense, Denmark.
63
School of Medicine and Public Health, Faculty of Medicine and Health, University of Newcastle, Callaghan, New South Wales, Australia.
64
Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
65
Ludwig-Maximilians-University of Munich, Dr. von Hauner Children's Hospital, Division of Metabolic Diseases and Nutritional Medicine, Munich, Germany.
66
Institute for Respiratory Health, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.
67
Ib-Salut, Area de Salut de Menorca, Institut d'Investigacio Sanitaria Illes Balears (IdISBa), Palma de Mallorca, Spain.
68
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
69
Channing Division of Network Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA.
70
Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA.
71
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
72
Population Health Research Institute, St George's, University of London, London, UK.
73
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. kb@copsac.com.

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.

PMID:
30013184
DOI:
10.1038/s41588-018-0157-1
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