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

Nature Genetics volume 47, pages 1449–1456 (2015)Cite this article

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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.

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Figure 1: Atopic dermatitis GWAS meta-analysis results.

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Acknowledgements

This publication is the work of the authors, and L.P. will serve as guarantor for the contents of this paper. This research was specifically funded by an MRC Population Health Scientist Fellowship awarded to L.P. (MR/J012165/1). D.M.E. is supported by an Australian Research Council Future Fellowship (FT130101709) and a Medical Research Council program grant (MC_UU_12013/4). Individual study acknowledgment and funding statements can be found in the Supplementary Note.

Author information

Author notes

  1. Lavinia Paternoster, Marie Standl and Sara J Brown: These authors contributed equally to this work.

  2. David M Evans and Stephan Weidinger: These authors jointly supervised this work.

Authors and Affiliations

  1. Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK

    Lavinia Paternoster, John P Kemp, Jie Zheng, George Davey Smith, Caroline L Relton & David M Evans

  2. School of Social and Community Medicine, University of Bristol, Bristol, UK

    Lavinia Paternoster, Wendy L McArdle, A John Henderson, John P Kemp, Jie Zheng, George Davey Smith & David M Evans

  3. Institute of Epidemiology I, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany

    Marie Standl, Carla M T Tiesler, Elisabeth Thiering & Joachim Heinrich

  4. Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

    Johannes Waage, Klaus Bønnelykke, Eskil Kreiner-Møller & Hans Bisgaard

  5. Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Hansjörg Baurecht, Melanie Hotze, Elke Rodríguez, Regina Fölster-Holst & Stephan Weidinger

  6. Population Health Research Institute, St. George's, University of London, London, UK

    David P Strachan

  7. Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester and University Hospital of South Manchester National Health Service (NHS) Foundation Trust, Manchester, UK

    John A Curtin, Adnan Custovic & Angela Simpson

  8. 23andMe, Inc., Mountain View, California, USA

    Chao Tian, Joyce Y Tung & David A Hinds

  9. Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan

    Atsushi Takahashi

  10. Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany

    Jorge Esparza-Gordillo, Ingo Marenholz, Birgit Kalb, Anja Matanovic, Franz Rüschendorf, Anja Bauerfeind, Norbert Hübner & Young-Ae Lee

  11. Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité–Universitätsmedizin Berlin, Berlin, Germany

    Jorge Esparza-Gordillo, Ingo Marenholz, Anja Matanovic & Young-Ae Lee

  12. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK

    Alexessander Couto Alves

  13. Department of Dermatology and Allergology, National Allergy Research Centre, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

    Jacob P Thyssen

  14. Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands

    Herman T den Dekker, Johan C de Jongste, Vincent W V Jaddoe & Liesbeth Duijts

  15. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

    Herman T den Dekker, Fernando Rivadeneira, Albert Hofman, Vincent W V Jaddoe, André G Uitterlinden & Liesbeth Duijts

  16. Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands

    Herman T den Dekker, Fernando Rivadeneira, Vincent W V Jaddoe, Niels J Elbert & Liesbeth Duijts

  17. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    Manuel A Ferreira & Nicholas G Martin

  18. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany

    Elisabeth Altmaier & Christian Gieger

  19. Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany

    Elisabeth Altmaier, Annette Peters & Christian Gieger

  20. Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany

    Elisabeth Altmaier, Janina S Ried & Christian Gieger

  21. Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

    Patrick M A Sleiman, Jin Li & Hakon Hakonarson

  22. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Patrick M A Sleiman & Hakon Hakonarson

  23. Institute of Dermatology, Anhui Medical University, Hefei, China

    Feng Li Xiao, Xian Bo Zuo, Xiao Dong Zheng, Xian Yong Yin, Liang Dan Sun & Xue Jun Zhang

  24. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain

    Juan R Gonzalez, Mariona Bustamante, Natàlia Vilor-Tejedor & Jordi Sunyer

  25. Pompeu Fabra University (UPF), Barcelona, Spain

    Juan R Gonzalez, Mariona Bustamante, Natàlia Vilor-Tejedor & Jordi Sunyer

  26. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

    Juan R Gonzalez, Mariona Bustamante, Natàlia Vilor-Tejedor & Jordi Sunyer

  27. Pediatric Pneumology and Immunology, Charité–Universitätsmedizin Berlin, Berlin, Germany

    Birgit Kalb & Susanne Lau

  28. Department of Medicine, University of California, San Francisco, San Francisco, California, USA

    Maria Pino-Yanes, Donglei Hu, Celeste Eng, Scott Huntsman & Esteban G Burchard

  29. Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain

    Maria Pino-Yanes

  30. Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain

    Maria Pino-Yanes

  31. Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), the Netherlands

    Cheng-Jian Xu & Dirkje S Postma

  32. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), the Netherlands

    Cheng-Jian Xu

  33. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

    Lisbeth Carstensen, Bjarke Feenstra, Frank Geller & Mads Melbye

  34. Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, the Netherlands

    Maria M Groen-Blokhuis, Jouke Jan Hottenga, Christel M Middeldorp & Dorret I Boomsma

  35. King's College London Department of Twin Research and Genetic Epidemiology, King's College London, London, UK

    Cristina Venturini, Pirro Hysi, Veronique Bataille, Tim Spector & Daniel Glass

  36. School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia

    Craig E Pennell & Carol A Wang

  37. Medical Research Council (MRC) Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK

    Sheila J Barton & Keith M Godfrey

  38. Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA

    Albert M Levin

  39. Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland

    Ivan Curjuric, Ashish Kumar, Medea Imboden & Nicole M Probst-Hensch

  40. University of Basel, Basel, Switzerland

    Ivan Curjuric, Ashish Kumar, Medea Imboden & Nicole M Probst-Hensch

  41. Centre for Genomic Regulation (CRG), Barcelona, Spain

    Mariona Bustamante

  42. Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK

    Gabrielle A Lockett & John W Holloway

  43. Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, Gothenburg, Sweden

    Jonas Bacelis & Bo Jacobsson

  44. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA

    Supinda Bunyavanich

  45. Department of Human Genetics, University of Chicago, Chicago, Illinois, USA

    Rachel A Myers & Carole Ober

  46. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Ashish Kumar & Erik Melén

  47. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    Ashish Kumar & Momoko Horikoshi

  48. Laboratory for Respiratory and Allergic Diseases, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan

    Tomomitsu Hirota & Mayumi Tamari

  49. Laboratory for Genotyping Development, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan

    Michiaki Kubo

  50. University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia

    John P Kemp & David M Evans

  51. Klinik für Kinder- und Jugendmedizin, Technical University Dresden, Dresden, Germany

    Min Ae Lee-Kirsch

  52. Clinic and Polyclinic of Dermatology, University Medicine Greifswald, Greifswald, Germany

    Andreas Arnold

  53. Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Germany

    Georg Homuth

  54. Institute for Community Medicine, Study of Health in Pomerania/KEF (Klinisch-Epidemiologische Forschung), University Medicine Greifswald, Greifswald, Germany

    Carsten O Schmidt

  55. Institute of Human Genetics, University of Bonn, Bonn, Germany

    Elisabeth Mangold, Sven Cichon & Markus M Nöthen

  56. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

    Sven Cichon & Markus M Nöthen

  57. Division of Medical Genetics, University Hospital Basel, Basel, Switzerland

    Sven Cichon

  58. Department of Biomedicine, University of Basel, Basel, Switzerland

    Sven Cichon

  59. Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organisation of the Brain, Genomic Imaging, Research Centre Jülich, Jülich, Germany

    Sven Cichon

  60. Institute of Social Medicine, Epidemiology and Health Economics, Charité–Universitätsmedizin Berlin, Berlin, Germany

    Thomas Keil

  61. Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany

    Thomas Keil

  62. DZHK (German Research Centre for Cardiovascular Research), Munich Heart Alliance, Munich, Germany

    Annette Peters

  63. Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany

    Andre Franke

  64. Institute of Epidemiology, Christian Albrechts University Kiel, Kiel, Germany

    Wolfgang Lieb

  65. Department of Dermatology and Allergy, University of Bonn Medical Center, Bonn, Germany

    Natalija Novak

  66. Unit of Living Environment and Health, National Institute for Health and Welfare, Kuopio, Finland

    Juha Pekkanen

  67. Department of Public Health, University of Helsinki, Helsinki, Finland

    Juha Pekkanen

  68. Center for Life-Course Epidemiology and Systems Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland

    Sylvain Sebert & Marjo-Riitta Jarvelin

  69. Biocenter Oulu, University of Oulu, Oulu, Finland

    Sylvain Sebert & Marjo-Riitta Jarvelin

  70. Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark

    Lise L Husemoen & Allan Linneberg

  71. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Niels Grarup

  72. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

    Fernando Rivadeneira & André G Uitterlinden

  73. Department of Dermatology, Erasmus University Medical Center, Rotterdam, the Netherlands

    Suzanne G M A Pasmans & Niels J Elbert

  74. Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia

    Guy B Marks

  75. Lung Institute of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia

    Philip J Thompson

  76. School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia

    Philip J Thompson

  77. Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia

    Melanie C Matheson

  78. Murdoch Childrens Research Institute, Melbourne, Victoria, Australia

    Colin F Robertson

  79. National Children's Research Centre, Crumlin, Dublin, Ireland

    Maeve A McAleer & Alan D Irvine

  80. Department of Pediatric Dermatology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland

    Maeve A McAleer, Grainne M O'Regan & Alan D Irvine

  81. Clinical Medicine, Trinity College Dublin, Dublin, Ireland

    Caoimhe M R Fahy & Alan D Irvine

  82. Centre for Dermatology and Genetic Medicine, University of Dundee, Dundee, UK

    Linda E Campbell, W H Irwin McLean & Sara J Brown

  83. Department of Biology and Medical Genetics, University Hospital Motol and 2nd Faculty of Medicine of Charles University, Prague, Czech Republic

    Milan Macek

  84. Department of Clinical Allergology, Pomeranian Medical University, Szczecin, Poland

    Michael Kurek

  85. Division of Metabolic Diseases and Nutritional Medicine, Ludwig Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany

    Carla M T Tiesler & Elisabeth Thiering

  86. Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan, USA

    Badri Pahukasahasram & L Keoki Williams

  87. School of Nursing, University of Michigan, Ann Arbor, Michigan, USA

    James J Yang

  88. Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK

    Caroline L Relton

  89. Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway

    Ronny Myhre, Wenche Nystad & Bo Jacobsson

  90. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Scott T Weiss & Benjamin A Raby

  91. Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA

    Deborah A Meyers

  92. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden

    Cilla Söderhäll

  93. Center for Innovative Medicine (CIMED), Karolinska Institutet, Stockholm, Sweden

    Cilla Söderhäll

  94. Sachs' Children's Hospital, Stockholm, Sweden

    Erik Melén

  95. Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK

    John W Holloway

  96. Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain

    Jordi Sunyer

  97. Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA

    L Keoki Williams

  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

    Keith M Godfrey

  99. Institute for Health and Care Research (EMGO), VU University, Amsterdam, the Netherlands

    Dorret I Boomsma

  100. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Mads Melbye & Allan Linneberg

  101. Department of Medicine, Stanford School of Medicine, Stanford, California, USA

    Mads Melbye

  102. Department of Pediatric Pulmonology and Pediatric Allergology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands

    Gerard H Koppelman

  103. Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK

    Deborah Jarvis

  104. Department of Epidemiology and Biostatistics, Medical Research Council–Public Health England Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

    Deborah Jarvis

  105. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA

    Esteban G Burchard

  106. Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark

    Allan Linneberg

  107. Department of Epidemiology and Biostatistics, Medical Research Council–Public Health England Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

    Marjo-Riitta Jarvelin

  108. Unit of Primary Care, Oulu University Hospital, Oulu, Finland

    Marjo-Riitta Jarvelin

  109. Department of Dermatology, Ninewells Hospital and Medical School, Dundee, UK

    Sara J Brown

Consortia

the EArly Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium

  • Lavinia Paternoster
  • , Marie Standl
  • , Johannes Waage
  • , Hansjörg Baurecht
  • , Melanie Hotze
  • , David P Strachan
  • , John A Curtin
  • , Klaus Bønnelykke
  • , Chao Tian
  • , Atsushi Takahashi
  • , Jorge Esparza-Gordillo
  • , Alexessander Couto Alves
  • , Jacob P Thyssen
  • , Herman T den Dekker
  • , Manuel A Ferreira
  • , Elisabeth Altmaier
  • , Patrick M A Sleiman
  • , Feng Li Xiao
  • , Juan R Gonzalez
  • , Ingo Marenholz
  • , Birgit Kalb
  • , Maria Pino-Yanes
  • , Cheng-Jian Xu
  • , Lisbeth Carstensen
  • , Maria M Groen-Blokhuis
  • , Cristina Venturini
  • , Craig E Pennell
  • , Sheila J Barton
  • , Albert M Levin
  • , Ivan Curjuric
  • , Mariona Bustamante
  • , Eskil Kreiner-Møller
  • , Gabrielle A Lockett
  • , Jonas Bacelis
  • , Supinda Bunyavanich
  • , Rachel A Myers
  • , Anja Matanovic
  • , Ashish Kumar
  • , Joyce Y Tung
  • , Tomomitsu Hirota
  • , Michiaki Kubo
  • , Wendy L McArdle
  • , A John Henderson
  • , John P Kemp
  • , Jie Zheng
  • , George Davey Smith
  • , Franz Rüschendorf
  • , Anja Bauerfeind
  • , Min Ae Lee-Kirsch
  • , Andreas Arnold
  • , Georg Homuth
  • , Carsten O Schmidt
  • , Elisabeth Mangold
  • , Sven Cichon
  • , Thomas Keil
  • , Elke Rodríguez
  • , Annette Peters
  • , Andre Franke
  • , Wolfgang Lieb
  • , Natalija Novak
  • , Regina Fölster-Holst
  • , Momoko Horikoshi
  • , Juha Pekkanen
  • , Sylvain Sebert
  • , Lise L Husemoen
  • , Niels Grarup
  • , Johan C de Jongste
  • , Fernando Rivadeneira
  • , Albert Hofman
  • , Vincent W V Jaddoe
  • , Suzanne G M A Pasmans
  • , Niels J Elbert
  • , André G Uitterlinden
  • , Guy B Marks
  • , Philip J Thompson
  • , Melanie C Matheson
  • , Colin F Robertson
  • , Australian Asthma Genetics Consortium(AAGC)
  • , Janina S Ried
  • , Jin Li
  • , Xian Bo Zuo
  • , Xiao Dong Zheng
  • , Xian Yong Yin
  • , Liang Dan Sun
  • , Maeve A McAleer
  • , Grainne M O'Regan
  • , Caoimhe M R Fahy
  • , Linda E Campbell
  • , Milan Macek
  • , Michael Kurek
  • , Donglei Hu
  • , Celeste Eng
  • , Dirkje S Postma
  • , Bjarke Feenstra
  • , Frank Geller
  • , Jouke Jan Hottenga
  • , Christel M Middeldorp
  • , Pirro Hysi
  • , Veronique Bataille
  • , Tim Spector
  • , Carla M T Tiesler
  • , Elisabeth Thiering
  • , Badri Pahukasahasram
  • , James J Yang
  • , Medea Imboden
  • , Scott Huntsman
  • , Natàlia Vilor-Tejedor
  • , Caroline L Relton
  • , Ronny Myhre
  • , Wenche Nystad
  • , Adnan Custovic
  • , Scott T Weiss
  • , Deborah A Meyers
  • , Cilla Söderhäll
  • , Erik Melén
  • , Carole Ober
  • , Benjamin A Raby
  • , Angela Simpson
  • , Bo Jacobsson
  • , John W Holloway
  • , Hans Bisgaard
  • , Jordi Sunyer
  • , Nicole M Probst-Hensch
  • , L Keoki Williams
  • , Keith M Godfrey
  • , Carol A Wang
  • , Dorret I Boomsma
  • , Mads Melbye
  • , Gerard H Koppelman
  • , Deborah Jarvis
  • , W H Irwin McLean
  • , Alan D Irvine
  • , Xue Jun Zhang
  • , Hakon Hakonarson
  • , Christian Gieger
  • , Esteban G Burchard
  • , Nicholas G Martin
  • , Liesbeth Duijts
  • , Allan Linneberg
  • , Marjo-Riitta Jarvelin
  • , Markus M Nöthen
  • , Susanne Lau
  • , Norbert Hübner
  • , Young-Ae Lee
  • , Mayumi Tamari
  • , David A Hinds
  • , Daniel Glass
  • , Sara J Brown
  • , Joachim Heinrich
  • , David M Evans
  •  & Stephan Weidinger

Contributions

Conceived and designed the experiments: L.P., M.S., H. Baurecht, D.P.S., J.A.C., K.B., J.P.T., H.T.d.D., P.M.A.S., F.L.X., M.B., J.Y.T., A.J.H., G.D.S., E.R., J.P., L.L.H., J.C.d.J., F. Rivadeneira, A.H., V.W.V.J., S.G.M.A.P., N.J.E., A.G.U., D.S.P., B.F., A.C., D.A.M., E. Melén, C.O., A.S., B.J., J.W.H., H. Bisgaard, J.S., N.M.P.-H., L.K.W., K.M.G., D.I.B., M. Melbye, G.H.K., Y.-A.L., N.H., D.J., X.J.Z., H.H., L.D., A.L., M.-R.J., M.T., S.J. Brown, J.H., D.M.E., S.W.

Performed the experiments: L.P., K.B., P.M.A.S., F.L.X., M.B., E.K.-M., G.A.L., M. Kubo, W.L.M., J.P.K., J.Z., E.R., F. Rivadeneira, A.G.U., J.L., X.Y.Y., L.D.S., L.E.C., A.M., C.E., D.S.P., C.M.T.T., M.I., S.H., N.V.-T., B.J., H. Bisgaard, N.M.P.-H., L.K.W., K.M.G., G.H.K., A.L., S.J. Brown, D.M.E., S.W.

Performed the statistical analysis: L.P., M.S., J.W., H. Baurecht, M. Hotze, D.P.S., J.A.C., C.T., A.T., A.B., A.C.A., H.T.d.D., M.A.F., E.A., P.M.A.S., J.R.G., I.M., J.E.-G., M.P.-Y., C.-J.X., L.C., M.M.G.-B., C.V., S.J. Barton, A.M.L., I.C., E.K.-M., G.A.L., S.B., R.A.M., F. Rüschendorf, A.K., J.P.K., J.Z., L.L.H., F. Rivadeneira, N.J.E., J.S.R., J.L., X.B.Z., X.D.Z., D.H., B.F., F.G., P.H., C.M.T.T., E.T., B.P., J.J.Y., N.V.-T., R.M., C.A.W., L.D., D.A.H., D.M.E.

Analyzed the data: L.P., M.S., J.W., H. Baurecht, M. Hotze, D.P.S., J.A.C., K.B., C.T., A.B., A.C.A., J.P.T., H.T.d.D., M.A.F., E.A., P.M.A.S., F.L.X., J.R.G., I.M., J.E.-G., M.P.-Y., C.-J.X., L.C., M.M.G.-B., C.V., S.J. Barton, A.M.L., I.C., G.A.L., J.B., S.B., R.A.M., F. Rüschendorf, A.K., A.J.H., M. Horikoshi, S.S., L.L.H., F. Rivadeneira, N.J.E., A.G.U., M.C.M., J.S.R., J.L., X.B.Z., X.D.Z., X.Y.Y., D.H., B.F., F.G., J.J.H., C.M.M., P.H., C.M.T.T., E.T., B.P., J.J.Y., M.I., S.H., N.V.-T., E. Melén, B.J., L.K.W., C.A.W., Y.-A.L., N.H., L.D., A.L., M.T., D.A.H., D.G., S.J. Brown, D.M.E.

Contributed reagents, material and/or analysis tools: L.P., J.W., H. Baurecht, M. Hotze, C.T., H.T.d.D., P.M.A.S., M.P.-Y., C.E.P., A.M.L., M.B., S.B., T.H., M. Kubo, W.L.M., J.Z., G.D.S., M. Macek, M. Kurek, M.A.L.-K., E. Mangold, A.P., A.F., W.L., N.N., R.F.-H., N.G., J.C.d.J., F. Rivadeneira, A.H., V.W.V.J., S.G.M.A.P., N.J.E., A.G.U., G.B.M., P.J.T., C.F.R., J.L., L.D.S., M.A.M., G.M.O'R., C.M.R.F., A.A., G.H., C.O.S., B.K., D.H., C.E., D.S.P., V.B., T.S., B.P., J.J.Y., C.L.R., S.T.W., D.A.M., S.C., T.K., C.S., E. Melén, S.L., C.O., B.A.R., B.J., J.W.H., J.S., L.K.W., K.M.G., M. Melbye, G.H.K., Y.-A.L., N.H., D.J., W.H.I.M., A.D.I., X.J.Z., H.H., C.G., E.G.B., N.G.M., L.D., M.-R.J., M.M.N., M.T., D.A.H., S.J. Brown, J.H., S.W.

Wrote the manuscript: L.P., M.S., J.W., H. Baurecht, M. Hotze, D.P.S., J.A.C., K.B., A.J.H., S.J. Brown, D.M.E., S.W.

Revised and reviewed the paper: L.P., M.S., J.W., H. Baurecht, M. Hotze, D.P.S., J.A.C., K.B., C.T., A.T., A.B., A.C.A., J.P.T., H.T.d.D., M.A.F., E.A., P.M.A.S., F.L.X., J.R.G., I.M., J.E.-G., M.P.-Y., C.-J.X., L.C., M.M.G.-B., C.V., C.E.P., S.J. Barton, A.M.L., I.C., M.B., E.K.-M., G.A.L., S.B., R.A.M., F. Rüschendorf, A.K., J.Y.T., T.H., M. Kubo, W.L.M., A.J.H., J.P.K., J.Z., G.D.S., M. Macek, M. Kurek, M.A.L.-K., E. Mangold, E.R., A.P., A.F., W.L., N.N., R.F.-H., M. Horikoshi, J.P., S.S., L.L.H., N.G., J.C.d.J., F. Rivadeneira, A.H., V.W.V.J., S.G.M.A.P., N.J.E., A.G.U., G.B.M., P.J.T., M.C.M., C.F.R., J.S.R., J.L., X.B.Z., X.D.Z., X.Y.Y., L.D.S., M.A.M., G.M.O'R., C.M.R.F., L.E.C., A.A., G.H., A.M., C.O.S., B.K., D.H., C.E., D.S.P., B.F., F.G., J.J.H., C.M.M., P.H., V.B., T.S., C.M.T.T., E.T., B.P., J.J.Y., M.I., S.H., N.V.-T., C.L.R., R.M., W.N., A.C., S.T.W., D.A.M., S.C., T.K., C.S., E. Melén, S.L., C.O., B.A.R., A.S., B.J., J.W.H., H. Bisgaard, J.S., N.M.P.-H., L.K.W., K.M.G., C.A.W., D.I.B., M. Melbye, G.H.K., Y.-A.L., N.H., D.J., W.H.I.M., A.D.I., X.J.Z., H.H., C.G., E.G.B., N.G.M., L.D., A.L., M.-R.J., M.M.N., M.T., D.A.H., D.G., S.J. Brown, J.H., D.M.E., S.W.

AAGC provided results for the discovery analysis.

Corresponding author

Correspondence to Lavinia Paternoster.

Ethics declarations

Competing interests

C.T., D.A.H. and J.Y.T. are employees of and own stock or stock options in 23andMe, Inc. K.M.G. has received reimbursement for speaking at conferences sponsored by companies selling nutritional and pharmaceutical products. He is part of an academic consortium that has received funding from Abbott Nutrition, Nestec and Danone. The University of Groningen has received money for D.S.P. in the context of an unrestricted educational grant for research from AstraZeneca. Fees for consultancies were given to the University of Groningen by AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Takeda and TEVA. A.C. reports personal fees from AstraZeneca, personal fees from Novartis and personal fees from ThermoFisher given outside the context of the current manuscript. A.S. reports personal fees from GlaxoSmithKline and personal fees from ThermoFisher given outside the context of the current manuscript.

Additional information

A full list of members and affiliations is provided in the Supplementary Note.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8, Supplementary Tables 1–4, 11–16, 22 and 23, and Supplementary Note. (PDF 20319 kb)

Supplementary Tables 5–10

Look-ups of known SNPs for various autoimmune diseases. (XLSX 48 kb)

Supplementary Tables 17–21

Functional investigations of credible SNPs. (XLSX 190 kb)

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the EArly Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet 47, 1449–1456 (2015). https://doi.org/10.1038/ng.3424

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