Largest Worldwide Study on Eczema

« Scientists from the Helmholtz Zentrum München and the Cluster of ExcellenceInflammation at Interfaces” in Kiel in collaboration with researchers and clinicians from 14 different countries have succeeded in identifying ten genomic regions in which common gene variants increase the risk of eczema (atopic dermatitis). The findings of this largest ever genetic study on eczema, in which more than 50,000 patients and 300,000 healthy individuals were examined, have now been published on the website of Nature Genetics.

eczema-neck

Eczema, or atopic dermatitis, is a chronic inflammatory skin disease which is characterized by intense itching and recurrent eczematous lesions. It affects up to 20% of children and 10% of adults worldwide, and dramatically impacts the quality of life and psychosocial well-being of patients and their families. Although the precise causes are still insufficiently understood, it is well established that an inherited susceptibility is of utmost importance.

To get insights into the genetic risk factors of the disease, a research team composed of clinicians and scientists from 14 different countries studied the entire genome of more than 50,000 patients and 300,000 healthy individuals.

The study was led by Professor Stephan Weidinger, Cluster of Excellence “Inflammation at Interfaces” (Department of Dermatology, Kiel University and Universitätsklinikum Schleswig-Holstein, Kiel Campus), Dr. Marie Standl from the Helmholtz Zentrum München (German Research Center for Environmental Health, Munich) and Dr. Lavinia Paternoster (University of Bristol, UK), within the framework of the “EAGLE” Consortium (EArly Genetics and Lifecourse Epidemiology).

The researchers were able to identify ten new genetic regions in which variations influence the risk for eczema. They also observed differences between ethnic groups. “Through the cooperation with colleagues from Europe, America, Asia and Australia we had access to an extremely high amount of data from diverse populations” says Standl, “and the results are highly robust.”

“Inherited susceptibility for inflammatory diseases“

The majority of the genes identified play a role for the balance of the immune system and its response to environmental exposures, and also affect the risk for other inflammatory diseases. Study leader Weidinger: “Our results suggest that many people have an inherited susceptibility for inflammatory diseases in general. In these people, other inherited or environmental exposures are then responsible for this susceptibility to be expressed in the skin.”

Understanding gene function to improve diagnostics and therapy

A special challenge will now be to understand in detail the molecular mechanisms through which the identified genes increase the risk for inflammatory diseases and more specifically for eczema.

In addition, their interaction with lifestyle and environmental factors has yet to be clarified. “Only then will we be able to develop tests which facilitate the prediction of disease risk and the development of improved strategies for prevention and treatment, or to apply existing treatments in a more targeted fashion”, says study leader Weidinger.

Background

Eczema is one of the most common chronic diseases worldwide. In developed countries, up to two out of ten children and one out of ten adults are affected by this extremely itchy and debilitating skin disease.

The disease has an enormous impact on quality of life, and in addition increases the risk for other inflammatory diseases such as asthma, rhinitis or inflammatory bowel disease. According to the most recent analysis of the world health organisation, eczema is classified as the leading health burden attributable to skin diseases. The underlying mechanisms of eczema are not yet sufficiently understood, but eczema is assumed to be based on a strongly genetic background. The main pathomechanisms are a weakened and deficient skin barrier and inappropriate immune responses to environmental stimuli. These characteristics are mainly inherited. »

Publication :

Standl, M. et al. (2015). Multi-ethnic genome-wide association study of 21,000 cases and 95,000 controls identifies 10 novel risk loci for atopic dermatitis. Nature Genetics, DOI: 10.1038/ng.3424

Writers Team: Lavinia Paternoster1,2,111, Marie Standl3,111, Johannes Waage4, Hansjörg Baurecht5, Melanie Hotze5, David P Strachan6, John A Curtin7, Klaus Bønnelykke4, Chao Tian8, Atsushi Takahashi9, Jorge Esparza-Gordillo10,11, Alexessander Couto Alves12, Jacob P Thyssen13, Herman T den Dekker1416, Manuel A Ferreira17, Elisabeth Altmaier1820, Patrick M A Sleiman21,22, Feng Li Xiao23, Juan R Gonzalez2426, Ingo Marenholz10,11, Birgit Kalb10,27, Maria Pino-Yanes2830, Cheng-Jian Xu31,32, Lisbeth Carstensen33, Maria M Groen-Blokhuis34, Cristina Venturini35, Craig E Pennell36, Sheila J Barton37, Albert M Levin38, Ivan Curjuric39,40, Mariona Bustamante2426,41, Eskil Kreiner-Møller4, Gabrielle A Lockett42, Jonas Bacelis43, Supinda Bunyavanich44, Rachel A Myers45, Anja Matanovic10,11, Ashish Kumar39,40,46,47, Joyce Y Tung8, Tomomitsu Hirota48, Michiaki Kubo49, Wendy L McArdle2, A John Henderson2, John P Kemp1,2,50, Jie Zheng1,2, George Davey Smith1,2, Franz Rüschendorf10, Anja Bauerfeind10, Min Ae Lee-Kirsch51, Andreas Arnold52, Georg Homuth53, Carsten O Schmidt54, Elisabeth Mangold55, Sven Cichon5559, Thomas Keil60,61, Elke Rodríguez5, Annette Peters19,62, Andre Franke63, Wolfgang Lieb64, Natalija Novak65, Regina Fölster-Holst5, Momoko Horikoshi47, Juha Pekkanen66,67, Sylvain Sebert68,69, Lise L Husemoen70, Niels Grarup71, Johan C de Jongste14, Fernando Rivadeneira15,16,72, Albert Hofman15, Vincent W V Jaddoe1416, Suzanne G M A Pasmans73, Niels J Elbert16,73, André G Uitterlinden15,72, Guy B Marks74, Philip J Thompson75,76, Melanie C Matheson77, Colin F Robertson78, Australian Asthma Genetics Consortium (AAGCGC)79, Janina S Ried20, Jin Li21, Xian Bo Zuo23, Xiao Dong Zheng23, Xian Yong Yin23, Liang Dan Sun23, Maeve A McAleer80,81, Grainne M O’Regan81, Caoimhe M R Fahy82, Linda E Campbell83, Milan Macek84, Michael Kurek85, Donglei Hu28, Celeste Eng28, Dirkje S Postma31, Bjarke Feenstra33, Frank Geller33, Jouke Jan Hottenga34, Christel M Middeldorp34, Pirro Hysi35, Veronique Bataille35, Tim Spector35, Carla M T Tiesler3,86, Elisabeth Thiering3,86, Badri Pahukasahasram87, James J Yang88, Medea Imboden39,40, Scott Huntsman28, Natàlia Vilor-Tejedor2426, Caroline L Relton1,89, Ronny Myhre90, Wenche Nystad90, Adnan Custovic7, Scott T Weiss91, Deborah A Meyers92, Cilla Söderhäll93,94, Erik Melén46,95, Carole Ober45, Benjamin A Raby91, Angela Simpson7, Bo Jacobsson43,90, John W Holloway42,96, Hans Bisgaard4, Jordi Sunyer2426,97, Nicole M Probst-Hensch39,40, L Keoki Williams87,98, Keith M Godfrey37,99, Carol A Wang36, Dorret I Boomsma34,100, Mads Melbye33,101,102, Gerard H Koppelman103, Deborah Jarvis104,105, W H Irwin McLean83, Alan D Irvine8082,Xue Jun Zhang23, Hakon Hakonarson21,22, Christian Gieger1820, Esteban G Burchard28,106, Nicholas G Martin17, Liesbeth Duijts1416, Allan Linneberg70,101,107, Marjo-Riitta Jarvelin68,69,108,109, Markus M Nöthen55,56, Susanne Lau27, Norbert Hübner10, Young-Ae Lee10,11, Mayumi Tamari48, David A Hinds8, Daniel Glass35, Sara J Brown83,110, Joachim Heinrich3, David M Evans1,2,50,112 & Stephan Weidinger5,112 for the EArly Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium.

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

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

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

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

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

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

7Centre 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
823andMe, Inc., Mountain View, California, USA

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

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

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

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

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

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

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

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

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

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

19Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
20Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
21Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

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

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

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

25Pompeu Fabra University (UPF), Barcelona, Spain

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

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

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

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

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

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

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

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

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

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

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

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

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

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

40University of Basel, Basel, Switzerland

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

69Biocenter Oulu, University of Oulu, Oulu, Finland

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

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

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

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

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

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

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

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

78Murdoch Childrens Research Institute, Melbourne, Victoria, Australia

79A full list of members and affiliations is provided in the Supplementary Note.

80National Children’s Research Centre, Crumlin, Dublin, Ireland

81Department of Pediatric Dermatology, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland

82Clinical Medicine, Trinity College Dublin, Dublin, Ireland

83Centre for Dermatology and Genetic Medicine, University of Dundee, Dundee, UK

84Department of Biology and Medical Genetics, University Hospital Motol and 2nd Faculty of Medicine of Charles University, Prague, Czech Republic

85Department of Clinical Allergology, Pomeranian Medical University, Szczecin, Poland

86Division of Metabolic Diseases and Nutritional Medicine, Ludwig Maximilians University of Munich, Dr. von Hauner Children’s Hospital, Munich, Germany

87Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan, USA

88School of Nursing, University of Michigan, Ann Arbor, Michigan, USA

89Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK

90Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway

91Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

92Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA

93Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden

94Center for Innovative Medicine (CIMED), Karolinska Institutet, Stockholm, Sweden

95Sachs’ Children’s Hospital, Stockholm, Sweden

96Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK

97Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain

98Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA

99National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK

100Institute for Health and Care Research (EMGO), VU University, Amsterdam, the Netherlands

101Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
102Department of Medicine, Stanford School of Medicine, Stanford, California, USA

103University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands

104Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK

105Department of Epidemiology and Biostatistics, Medical Research Council–Public Health England Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

106Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA
107Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark

108Department of Epidemiology and Biostatistics, Medical Research Council –Public Health England Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

109Unit of Primary Care, Oulu University Hospital, Oulu, Finland

110Department of Dermatology, Ninewells Hospital and Medical School, Dundee, UK


Sources:
http://www.alphagalileo.org/ViewItem.aspx?ItemId=157524&CultureCode=en
https://www.helmholtz-muenchen.de/en/news/latest-news/press-information-news/article/27895/index.html
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3424.html
http://www.aerzteblatt.de/nachrichten/64515/Neurodermitis-Neue-Risikogene-zeigen-Einfluss-des-Immunsystems
http://www.healthcanal.com/skin-hair-nails/67979-ten-new-genetic-risk-loci-for-eczema-discovered.html

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