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Nat Genet. 2015 Dec;47(12):1449-1456. doi: 10.1038/ng.3424. Epub 2015 Oct 19.

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.

Paternoster L#1,2, Standl M#3, Waage J4, Baurecht H5, Hotze M5, Strachan DP6, Curtin JA7, Bønnelykke K4, Tian C8, Takahashi A9, Esparza-Gordillo J10,11, Alves AC12, Thyssen JP13, den Dekker HT14,15,16, Ferreira MA17, Altmaier E18,19,20, Sleiman PM21,22, Xiao FL23, Gonzalez JR24, Marenholz I10,11, Kalb B10,25, Yanes MP26,27,28, Xu CJ29,30, Carstensen L31, Groen-Blokhuis MM32, Venturini C33, Pennell CE34, Barton SJ35, Levin AM36, Curjuric I37,38, Bustamante M24,39,40,41, Kreiner-Møller E4, Lockett GA42, Bacelis J43, Bunyavanich S44, Myers RA45, Matanovic A10,11, Kumar A37,38,46,47, Tung JY8, Hirota T48, Kubo M49, McArdle WL2, Henderson AJ2, Kemp JP1,2,50, Zheng J1,2, Smith GD1,2, Rüschendorf F10, Bauerfeind A10, Lee-Kirsch MA51, Arnold A52, Homuth G53, Schmidt CO54, Mangold E55, Cichon S55,56,57,58,59, Keil T60,61, Rodríguez E5, Peters A19,62, Franke A63, Lieb W64, Novak N65, Fölster-Holst R5, Horikoshi M47, Pekkanen J66,67, Sebert S68,69, Husemoen LL70, Grarup N71, de Jongste JC14, Rivadeneira F15,16,72, Hofman A15, Jaddoe VW14,15,16, Pasmans SG73, Elbert NJ16,73, Uitterlinden AG15,72, Marks GB74, Thompson PJ75,76, Matheson MC77, Robertson CF78; Australian Asthma Genetics Consortium (AAGC), Ried JS20, Li J21, Zuo XB23, Zheng XD23, Yin XY23, Sun LD23, McAleer MA79,80, O'Regan GM80, Fahy CM81, Campbell LE82, Macek M83, Kurek M84, Hu D26, Eng C26, Postma DS29, Feenstra B31, Geller F31, Hottenga JJ32, Middeldorp CM32, Hysi P33, Bataille V33, Spector T33, Tiesler CM3,85, Thiering E3,85, Pahukasahasram B86, Yang JJ87, Imboden M37,38, Huntsman S26, Vilor-Tejedor N24,40,41, Relton CL1,88, Myhre R89, Nystad W89, Custovic A7, Weiss ST90, Meyers DA91, Söderhäll C92,93, Melén E46,94, Ober C45, Raby BA90, Simpson A7, Jacobsson B43,89, Holloway JW42,95, Bisgaard H4, Sunyer J24,40,41,96, Hensch NMP37,38, Williams LK86,97, Godfrey KM35,98, Wang CA34, Boomsma DI32,99, Melbye M31,100,101, Koppelman GH102, Jarvis D103,104, McLean WI82, Irvine AD79,80,81, Zhang XJ23, Hakonarson H21,22, Gieger C18,19,20, Burchard EG26,105, Martin NG17, Duijts L14,15,16, Linneberg A70,100,106, Jarvelin MR69,107,108,109, Noethen MM55,56, Lau S25, Hübner N10, Lee YA10,11, Tamari M48, Hinds DA8, Glass D33, Brown SJ82,110, Heinrich J3, Evans DM1,2,50,111, Weidinger S5,111.

Author information

1
Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
2
School of Social and Community Medicine, University of Bristol, Bristol, UK.
3
Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
4
Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
5
Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
6
Population Health Research Institute, St George's, University of London, London, UK.
7
Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
8
23andMe, Inc., Mountain View, CA, USA.
9
Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
10
Max-Delbrück-Center (MDC) for Molecular Medicine, Berlin, Germany.
11
Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
12
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
13
National Allergy Research Centre, Department of Dermatology and Allergology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
14
Department of Pediatrics, Erasmus MC, Rotterdam, the Netherlands.
15
Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
16
The Generation R Study Group, Erasmus MC, Rotterdam, the Netherlands.
17
QIMR Berghofer Medical Research Institute, Brisbane, Australia.
18
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
19
Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
20
Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
21
The Center for Applied Genomics, The Children's Hospital of Philadelphia, PA, USA.
22
Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
23
Institute of Dermatology, Anhui Medical University, Hefei, Anhui, China.
24
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
25
Pediatric Pneumology and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
26
Department of Medicine, University of California, San Francisco, CA, USA.
27
Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
28
Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
29
University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
30
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
31
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
32
Dept Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, the Netherlands.
33
KCL Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
34
School of Women's and Infants' Health, The University of Western Australia (UWA), Perth, Australia.
35
Medical Research Council (MRC) Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
36
Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
37
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.
38
University of Basel, Basel, Switzerland.
39
Centre for Genomic Regulation (CRG), Barcelona, Spain.
40
Pompeu Fabra University (UPF), Barcelona, Spain.
41
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
42
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
43
Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hosptial, Gothenburg, Sweden.
44
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
45
Department of Human Genetics, University of Chicago, Chicago, IL, USA.
46
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
47
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
48
Laboratory for Respiratory and Allergic Diseases, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
49
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
50
University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Australia.
51
Klinik für Kinder- und Jugendmedizin, Technical University Dresden, Dresden, Germany.
52
Clinic and Polyclinic of Dermatology, University Medicine Greifswald, Greifswald, Germany.
53
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
54
Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald, Greifswald, Germany.
55
Institute of Human Genetics, University of Bonn, Bonn, Germany.
56
Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
57
Division of Medical Genetics, University Hospital Basel, Basel, Switzerland.
58
Department of Biomedicine, University of Basel, Basel, Switzerland.
59
Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organisation of the Brain, Genomic Imaging, Research Centre Jülich, Jülich, Germany.
60
Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
61
Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
62
Deutsches Forschungszentrum für Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, Munich, Germany.
63
Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
64
Institute of Epidemiology, Christian-Albrechts University Kiel, Kiel, Germany.
65
Department of Dermatology and Allergy, University of Bonn Medical Center, Bonn, Germany.
66
Unit of Living Environment and Health, National Institute for Health and Welfare, Kuopio, Finland.
67
Department of Public Health, University of Helsinki, Helsinki, Finland.
68
Center for Life-course and Systems Epidemiology, Faculty of Medicine, University of Oulu, Finland.
69
Biocenter Oulu, University of Oulu, Finland.
70
Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark.
71
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
72
Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
73
Department of Dermatology, Erasmus MC, Rotterdam, the Netherlands.
74
Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia.
75
Lung Institute of Western Australia, QE II Medical Centre Nedlands , Western Australia, Australia.
76
School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
77
Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
78
Murdoch Children's Research Institute, Melbourne, Australia.
79
National Children's Research Centre, Crumlin, Dublin, Ireland.
80
Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
81
Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
82
Centre for Dermatology and Genetic Medicine, University of Dundee, Dundee, UK.
83
Department of Biology and Medical Genetics, University Hospital Motol and 2nd Faculty of Medicine of Charles University, Prague, Czech Republic.
84
Department of Clinical Allergology, Pomeranian, Pomeranian Medical University, Szczecin, Poland.
85
Ludwig-Maximilians-University of Munich, Dr. von Hauner Children's Hospital, Division of Metabolic Diseases and Nutritional Medicine, Munich, Germany.
86
Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA.
87
School of Nursing, University of Michigan, Ann Arbor, MI, USA.
88
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
89
Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
90
Channing Division of Network Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA.
91
Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
92
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
93
Center for Innovative Medicine (CIMED), Karolinska Institutet, Stockholm, Sweden.
94
Sachs' Children's Hospital, Stockholm, Sweden.
95
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
96
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
97
Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA.
98
National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK.
99
Institute for Health and Care Research (EMGO), VU University, Amsterdam, the Netherlands.
100
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
101
Department of Medicine, Stanford School of Medicine, Stanford, California, USA.
102
University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Department of Pediatric Pulmonology and Pediatric Allergology, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
103
Respiratory Epidemiology, Occupational Medicine and Public Health; National Heart and Lung Institute; Imperial College; London, UK.
104
Medical Research Council-Public Health England Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
105
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
106
Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark.
107
Department of Epidemiology and Biostatistics, Medical Research Council (MRC) Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
108
Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland.
109
Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
110
Department of Dermatology, Ninewells Hospital and Medical School, Dundee, UK.
111
These authors jointly directed this work.
#
Contributed equally

Abstract

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.

PMID:
26482879
PMCID:
PMC4753676
DOI:
10.1038/ng.3424
[Indexed for MEDLINE]
Free PMC Article

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