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Nat Genet. 2013 Aug;45(8):902-906. doi: 10.1038/ng.2694. Epub 2013 Jun 30.

Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization.

Author information

1
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood; Health Sciences, University of Copenhagen & Copenhagen University Hospital, Gentofte, Denmark.
2
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Australia.
3
Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark.
4
Division of Endocrinology, Children's Hospital, Boston, USA.
5
Center for Basic and Translational Obesity Research, Children's Hospital, Boston, USA.
6
Broad Institute, Cambridge, USA.
7
School of Social and Community Medicine, University of Bristol, Bristol, UK.
8
Division of Population Health Sciences & Education, St George's, University of London, London, UK.
9
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK.
10
Research Centre for Prevention and Health, Glostrup Hospital, Glostrup, Denmark.
11
University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
12
School of Women's and Infants' Health, The University of Western Australia, Crawley, Australia.
13
Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
14
Department of Epidemiology, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
15
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
16
University of Iceland, 101 Reykjavik, Iceland.
17
General Hospital "Dr Josip Bencevic" Slavonski Brod, University of Osijek, Osijek, Croatia.
18
Institute of Health Sciences, University of Oulu, Oulu, Finland.
19
Biocenter Oulu, University of Oulu, Oulu, Finland.
20
Center for Applied Genomics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
21
Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
22
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
23
Lung Institute of WA, University of WA, Perth, Western Australia, Australia.
24
Centre for Asthma, Allergy and Respiratory Research, University of WA, Perth, Western Australia, Australia.
25
PathWest Laboratory Medicine of Western Australia (WA), Nedlands, Australia.
26
School of Population Health, The University of WA, Nedlands, Australia.
27
School of Pathology and Laboratory Medicine, The University of WA, Nedlands, Australia.
28
Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
29
School of Medicine, University of Tasmania, Hobart, Australia.
30
Queensland Institute of Medical Research, Brisbane, Australia.
31
School of Science and Health, University of Western Sydney, Penrith, Australia.
32
Respiratory Medicine, Murdoch Children's Research Institute, Melbourne, Australia.
33
Department of Environmental Health, National Institute for Health and Welfare (THL), Kuopio, Finland.
34
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
35
Department of Clinical Sciences, Obstetrics and Gynecology, Institute of Clinical Medicine, University of Oulu, Oulu, Finland.
36
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
37
School of Medicine and Pharmacology, University of WA, Nedlands, Australia.
38
Department of Pulmonary Physiology, West Australian Sleep Disorders Research Institute, Nedlands, Australia.
39
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
40
Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia.
41
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
42
Telethon Institute for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.
43
Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia.
44
Queensland Children's Medical Research Institute, University of Queensland, World Health Organization (WHO) Collaborating Centre for Research on Children's Environmental Health, Australia.
45
Division of Genetics, Children's Hospital, Boston, USA.
46
Department of Genetics, Harvard Medical School, Boston, USA.
47
Department of Dermatology, Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
48
Department of Pulmonology, GRIAC, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
49
Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environment and Health, Imperial College London, UK.
50
National Institute of Health and Welfare, Oulu, Finland.
51
Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
52
Department of Pediatric Pulmonology and Pediatric Allergology , Beatrix Children's Hospital, GRIAC, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
#
Contributed equally

Abstract

Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up the top SNP at each of 26 loci in 6,114 affected individuals and 9,920 controls. We increased the number of susceptibility loci with genome-wide significant association with allergic sensitization from three to ten, including SNPs in or near TLR6, C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2 and HLA-B. All the top SNPs were associated with allergic symptoms in an independent study. Risk-associated variants at these ten loci were estimated to account for at least 25% of allergic sensitization and allergic rhinitis. Understanding the molecular mechanisms underlying these associations may provide new insights into the etiology of allergic disease.

PMID:
23817571
PMCID:
PMC4922420
DOI:
10.1038/ng.2694
[Indexed for MEDLINE]
Free PMC Article

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