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

Lavinia Paternoster^#^{1

2}, Marie Standl^#³, Johannes Waage⁴, Hansjörg Baurecht⁵, Melanie Hotze⁵, David P Strachan⁶, John A Curtin⁷, Klaus Bønnelykke⁴, Chao Tian⁸, Atsushi Takahashi⁹, Jorge Esparza-Gordillo^{10

11}, Alexessander Couto Alves¹², Jacob P Thyssen¹³, Herman T den Dekker^{14

15

16}, Manuel A Ferreira¹⁷, Elisabeth Altmaier^{18

19

20}, Patrick Ma Sleiman^{21

22}, Feng Li Xiao²³, Juan R Gonzalez²⁴, Ingo Marenholz^{10

11}, Birgit Kalb^{10

25}, Maria Pino Yanes^{26

27

28}, Cheng-Jian Xu^{29

30}, Lisbeth Carstensen³¹, Maria M Groen-Blokhuis³², Cristina Venturini³³, Craig E Pennell³⁴, Sheila J Barton³⁵, Albert M Levin³⁶, Ivan Curjuric^{37

38}, Mariona Bustamante^{24

39

40

41}, Eskil Kreiner-Møller⁴, Gabrielle A Lockett⁴², Jonas Bacelis⁴³, Supinda Bunyavanich⁴⁴, Rachel A Myers⁴⁵, Anja Matanovic^{10

11}, Ashish Kumar^{37

38

46

47}, Joyce Y Tung⁸, Tomomitsu Hirota⁴⁸, Michiaki Kubo⁴⁹, Wendy L McArdle², A J Henderson², John P Kemp^{1

2

50}, Jie Zheng^{1

2}, George Davey Smith^{1

2}, Franz Rüschendorf¹⁰, Anja Bauerfeind¹⁰, Min Ae Lee-Kirsch⁵¹, Andreas Arnold⁵², Georg Homuth⁵³, Carsten O Schmidt⁵⁴, Elisabeth Mangold⁵⁵, Sven Cichon^{55

56

57

58

59}, Thomas Keil^{60

61}, Elke Rodríguez⁵, Annette Peters^{19

62}, Andre Franke⁶³, Wolfgang Lieb⁶⁴, Natalija Novak⁶⁵, Regina Fölster-Holst⁵, Momoko Horikoshi⁴⁷, Juha Pekkanen^{66

67}, Sylvain Sebert^{68

69}, Lise L Husemoen⁷⁰, Niels Grarup⁷¹, Johan C de Jongste¹⁴, Fernando Rivadeneira^{15

16

72}, Albert Hofman¹⁵, Vincent Wv Jaddoe^{14

15

16}, Suzanne Gma Pasmans⁷³, Niels J Elbert^{16

73}, André G Uitterlinden^{15

72}, Guy B Marks⁷⁴, Philip J Thompson^{75

76}, Melanie C Matheson⁷⁷, Colin F Robertson⁷⁸; Australian Asthma Genetics Consortium (AAGC); Janina S Ried²⁰, Jin Li²¹, Xian Bo Zuo²³, Xiao Dong Zheng²³, Xian Yong Yin²³, Liang Dan Sun²³, Maeve A McAleer^{79

80}, Grainne M O'Regan⁸⁰, Caoimhe Mr Fahy⁸¹, Linda E Campbell⁸², Milan Macek⁸³, Michael Kurek⁸⁴, Donglei Hu²⁶, Celeste Eng²⁶, Dirkje S Postma²⁹, Bjarke Feenstra³¹, Frank Geller³¹, Jouke Jan Hottenga³², Christel M Middeldorp³², Pirro Hysi³³, Veronique Bataille³³, Tim Spector³³, Carla Mt Tiesler^{3

85}, Elisabeth Thiering^{3

85}, Badri Pahukasahasram⁸⁶, James J Yang⁸⁷, Medea Imboden^{37

38}, Scott Huntsman²⁶, Natàlia Vilor-Tejedor^{24

40

41}, Caroline L Relton^{1

88}, Ronny Myhre⁸⁹, Wenche Nystad⁸⁹, Adnan Custovic⁷, Scott T Weiss⁹⁰, Deborah A Meyers⁹¹, Cilla Söderhäll^{92

93}, Erik Melén^{46

94}, Carole Ober⁴⁵, Benjamin A Raby⁹⁰, Angela Simpson⁷, Bo Jacobsson^{43

89}, John W Holloway^{42

95}, Hans Bisgaard⁴, Jordi Sunyer^{24

40

41

96}, Nicole M Probst Hensch^{37

38}, L Keoki Williams^{86

97}, Keith M Godfrey^{35

98}, Carol A Wang³⁴, Dorret I Boomsma^{32

99}, Mads Melbye^{31

100

101}, Gerard H Koppelman¹⁰², Deborah Jarvis^{103

104}, Wh Irwin McLean⁸², Alan D Irvine^{79

80

81}, Xue Jun Zhang²³, Hakon Hakonarson^{21

22}, Christian Gieger^{18

19

20}, Esteban G Burchard^{26

105}, Nicholas G Martin¹⁷, Liesbeth Duijts^{14

15

16}, Allan Linneberg^{70

100

106}, Marjo-Riitta Jarvelin^{69

107

108

109}, Markus M Noethen^{55

56}, Susanne Lau²⁵, Norbert Hübner¹⁰, Young-Ae Lee^{10

11}, Mayumi Tamari⁴⁸, David A Hinds⁸, Daniel Glass³³, Sara J Brown^{82

110}, Joachim Heinrich³, David M Evans^{1

2

50

111}, Stephan Weidinger^{5

111}

Affiliations

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.

PMID: 26482879
PMCID: PMC4753676
DOI: 10.1038/ng.3424

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

Lavinia Paternoster et al. Nat Genet. 2015 Dec.

. 2015 Dec;47(12):1449-1456.

doi: 10.1038/ng.3424. Epub 2015 Oct 19.

Authors

Affiliations

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.

PMID: 26482879
PMCID: PMC4753676
DOI: 10.1038/ng.3424

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.

PubMed Disclaimer

Figures

**Figure 1. Atopic dermatitis GWAS meta-analysis results**
(A) Manhattan plot of European fixed effects meta-analysis. (B) Manhattan plot of the multi-ethnic MANTRA meta-analysis of all studies. Arrows mark variants not associated in the European-only analysis. (C) QQ plot of the European analysis - lambda=1.054.

See this image and copyright information in PMC

References

1. Bieber T. Atopic dermatitis. New Engl J Med. 2008;358:1483–94. - PubMed
1. Bataille V, Lens M, Spector TD. The use of the twin model to investigate the genetics and epigenetics of skin diseases with genomic, transcriptomic and methylation data. J Eur Acad Dermatol Venereol. 2012;26:1067–73. - PubMed
1. Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011;365:1315–27. - PubMed
1. Palmer CNA, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature genetics. 2006;38:441–6. - PubMed
1. Rodriguez E, et al. Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. J Allergy Clin Immunol. 2009;123:1361–70. e7. - PubMed

Methods-only references

1. Morris AP. Transethnic meta-analysis of genomewide association studies. Genet Epidemiol. 2011;35:809–22. - PMC - PubMed
1. Wang X, et al. Comparing methods for performing trans-ethnic meta-analysis of genome-wide association studies. Hum Mol Genet. 2013;22:2303–11. - PubMed
1. Yang J, et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat Genet. 2012;44:369–75. S1–3. - PMC - PubMed
1. Nyholt DR. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet. 2004;74:765–9. - PMC - PubMed
1. Welter D, et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res. 2014;42:D1001–6. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Molecular Biology Databases
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

Methods-only references

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases