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Ten new Genetic Risk Loci for Eczema Discovered – International Study with 50,000 Eczema Patients

20.10.2015

Researchers in Europe, Australia, Asia, and America have now discovered ten new risk loci for the chronic inflammatory skin disease eczema. Among the new candidate genes for eczema, the researchers came upon genes that are important for the innate immune system and for the development and function of T-cells which play an important role in specific immune responses. This emphasizes the importance of the immune system in the onset and progression of eczema. With the newly identified risk regions, a total of 31 risk regions for eczema are now known (Nature Genetics, doi:10.1038/ng3424)⃰ .

In a genome-wide association study over 15 million genetic variants across all chromosomes were examined for their role in eczema susceptibility. The frequency of each variant was compared in almost 21,400 eczema patients and 95,000 healthy controls from Europe, Africa, Japan, and Latin America in the first part of the study. An additional 260,000 participants were examined to confirm the results. Geneticist and pediatrician Prof. Young-Ae Lee from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and Charité – Universitätsmedizin Berlin coordinated the study for Berlin.

Eczema, also called atopic dermatitis, is a chronic inflammatory skin disorder affecting about 15-30 percent of children and 5-10 percent of adults in industrialized countries. Researchers estimate that genetic factors account for about two-thirds of the disease risk. Onset of eczema typically occurs within the first few years of life. It usually presents in recurrent flares that are characterized by itchy, inflammatory skin lesions. Although eczema often improves or resolves with age, children with eczema carry a high risk of developing other allergic disorders such as fever and asthma in subsequent years.

The newly identified genetic regions show a strong correlation with known risk loci for asthma, allergies, and other chronic inflammatory diseases like Crohn’s disease and psoriasis, as well as with autoimmune disorders. The study also confirmed known hereditary risk factors that impair the barrier function of the skin. Genes in these genetic locations play an important role in the detection and defense against microbes and in the development and activation of T-cells. Overall, the study emphasizes the importance of the immune system in the development and progression of eczema.

... more about:
»Dermatology »Epidemiology »Genetic »Medicine

⃰ Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis
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 Dekker14–16, Manuel A Ferreira17, Elisabeth Altmaier18–20, Patrick M A Sleiman21,22, Feng Li Xiao23, Juan R Gonzalez24–26, Ingo Marenholz10,11, Birgit Kalb10,27, Maria Pino-Yanes28–30, 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 Bustamante24–26,41, 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 Cichon55–59, 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 Jaddoe14–16, 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-Tejedor24–26, 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 Sunyer24–26,97, 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 Irvine80–82,Xue Jun Zhang23, Hakon Hakonarson21,22, Christian Gieger18–20, Esteban G Burchard28,106, Nicholas G Martin17, Liesbeth Duijts14–16, 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

Contact:
Barbara Bachtler
Press Department
Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
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Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/en

Barbara Bachtler | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft

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