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Nat Commun. 2015 Nov 6;6:8804. doi: 10.1038/ncomms9804.

Meta-analysis identifies seven susceptibility loci involved in the atopic march.

Author information

1
Max-Delbrück-Center (MDC) for Molecular Medicine, Berlin, Germany.
2
Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité University Medical Center, Berlin, Germany.
3
Population Health Research Institute, St George's, University of London, London, UK.
4
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
5
Department of Dermatology, Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
6
Inserm, UMR-946, F-75010 Paris, France.
7
Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, F-75007 Paris, France.
8
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
9
University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
10
Dr von Hauner Children's Hospital, Ludwig Maximilians University Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
11
Lung Institute of Western Australia, University of Western Australia, Perth, Western Australia, Australia.
12
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Victoria, Australia.
13
Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
14
Department of Pediatric Pneumology and Allergy, University Children`s Hospital Regensburg (KUNO), Regensburg, Germany.
15
School of Women and Infant's Health, University of Western Australia, Perth, Western Australia, Australia.
16
School of Social and Community Medicine, University of Bristol, Bristol, UK.
17
Clinic and Polyclinic of Dermatology, University Medicine Greifswald, Greifswald, Germany.
18
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
19
Department of Biosciences and Nutrition, and Center for Innovative Medicine (CIMED), Karolinska Institutet, Stockholm, Sweden.
20
Department of Pediatrics, Pediatric Chest Center, Erasmus University Medical Center, Rotterdam, The Netherlands.
21
Department of Pulmonology and GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
22
Swiss Tropical and Public Health Institute and the University of Basel, Basel, Switzerland.
23
Division of Pediatric Cardiology and Pulmonology, Department of Pediatrics, Innsbruck Medical University, Innsbruck, Austria.
24
Siberian State Medical University, Tomsk, Russia.
25
Research Institute of Medical Genetics, Tomsk, Russia.
26
Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
27
Centre de santé et de services sociaux de Chicoutimi, Saguenay, Québec, Canada.
28
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
29
Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
30
Department of Respiratory Medicine, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
31
Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
32
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
33
Department of Otolaryngology-Head and Neck Surgery, Temple University, School of Medicine, Philadelphia, Pennsylvania, USA.
34
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
35
Institute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany.
36
Research Unit of Molecular Epidemiology and Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
37
University Children's Hospital, Albert Ludwigs University, Freiburg, Germany.
38
University Children's Hospital, University of Cologne, Cologne, Germany.
39
Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany.
40
Institute for Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
41
Institute of Human Genetics, University of Bonn, Bonn, Germany.
42
Department of Genomics, Life &Brain Center, University of Bonn, Bonn, Germany.
43
Division of Medical Genetics, University Hospital Basel and Department of Biomedicine, University of Basel, Basel, Switzerland.
44
Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organisation of the Brain, Genomic Imaging, Research Centre Jülich, Jülich, Germany.
45
Queensland Children's Medical Research Institute, University of Queensland, Brisbane, Queensland, Australia.
46
Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald, Greifswald, Germany.
47
Max Planck Institute for Molecular Genetics, Berlin, Germany.
48
Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
49
Department of Pediatric Pneumology and Immunology, Charité University Medical Center, Berlin, Germany.
50
Université du Québec à Chicoutimi, Saguenay, Québec, Canada.
51
Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
52
Department of Pediatric Pulmonology and Pediatric Allergology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital and GRIAC Research Institute, Groningen, The Netherlands.
53
Sachs' Children's Hospital, Stockholm, Sweden.

Abstract

Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

PMID:
26542096
PMCID:
PMC4667629
DOI:
10.1038/ncomms9804
[Indexed for MEDLINE]
Free PMC Article

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