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

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Published in Nat Genet on October 19, 2015

Authors

Lavinia Paternoster1,2, Marie Standl3, 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 Dekker14,15,16, Manuel A Ferreira17, Elisabeth Altmaier18,19,20, Patrick Ma Sleiman21,22, Feng Li Xiao23, Juan R Gonzalez24, Ingo Marenholz10,11, Birgit Kalb10,25, Maria Pino Yanes26,27,28, Cheng-Jian Xu29,30, Lisbeth Carstensen31, Maria M Groen-Blokhuis32, Cristina Venturini33, Craig E Pennell34, Sheila J Barton35, Albert M Levin36, Ivan Curjuric37,38, Mariona Bustamante24,39,40,41, Eskil Kreiner-Møller4, Gabrielle A Lockett42, Jonas Bacelis43, Supinda Bunyavanich44, Rachel A Myers45, Anja Matanovic10,11, Ashish Kumar37,38,46,47, Joyce Y Tung8, Tomomitsu Hirota48, Michiaki Kubo49, Wendy L McArdle2, A J 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 Cichon55,56,57,58,59, 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 Wv Jaddoe14,15,16, Suzanne Gma 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 (AAGC), Janina S Ried20, Jin Li21, Xian Bo Zuo23, Xiao Dong Zheng23, Xian Yong Yin23, Liang Dan Sun23, Maeve A McAleer79,80, 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 Tiesler3,85, Elisabeth Thiering3,85, Badri Pahukasahasram86, James J Yang87, Medea Imboden37,38, Scott Huntsman26, Natàlia Vilor-Tejedor24,40,41, Caroline L Relton1,88, Ronny Myhre89, Wenche Nystad89, Adnan Custovic7, Scott T Weiss90, Deborah A Meyers91, Cilla Söderhäll92,93, Erik Melén46,94, Carole Ober45, Benjamin A Raby90, Angela Simpson7, Bo Jacobsson43,89, John W Holloway42,95, Hans Bisgaard4, Jordi Sunyer24,40,41,96, Nicole M Probst Hensch37,38, L Keoki Williams86,97, Keith M Godfrey35,98, Carol A Wang34, Dorret I Boomsma32,99, Mads Melbye31,100,101, Gerard H Koppelman102, Deborah Jarvis103,104, Wh Irwin McLean82, Alan D Irvine79,80,81, Xue Jun Zhang23, Hakon Hakonarson21,22, Christian Gieger18,19,20, Esteban G Burchard26,105, Nicholas G Martin17, Liesbeth Duijts14,15,16, Allan Linneberg70,100,106, Marjo-Riitta Jarvelin69,107,108,109, Markus M Noethen55,56, Susanne Lau25, Norbert Hübner10, Young-Ae Lee10,11, Mayumi Tamari48, David A Hinds8, Daniel Glass33, Sara J Brown82,110, Joachim Heinrich3, David M Evans1,2,50,111, Stephan Weidinger5,111, EArly Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium

Author 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.

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Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis. Hum Mol Genet (2016) 0.94

Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy. PLoS Genet (2015) 0.93

Gene-based pleiotropy across migraine with aura and migraine without aura patient groups. Cephalalgia (2015) 0.93

Genome-wide association studies in asthma; perhaps, the end of the beginning. Curr Opin Allergy Clin Immunol (2013) 0.92

DCAF4, a novel gene associated with leucocyte telomere length. J Med Genet (2015) 0.90

Early-onset Crohn's disease and autoimmunity associated with a variant in CTLA-4. Gut (2014) 0.90

Genetic investigations of sudden unexpected deaths in infancy using next-generation sequencing of 100 genes associated with cardiac diseases. Eur J Hum Genet (2015) 0.89

Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nat Neurosci (2016) 0.87

Meta-analysis identifies seven susceptibility loci involved in the atopic march. Nat Commun (2015) 0.86

DNA methylation loci associated with atopy and high serum IgE: a genome-wide application of recursive Random Forest feature selection. Genome Med (2015) 0.86

Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes. J Allergy Clin Immunol (2015) 0.85

Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene. PLoS Genet (2016) 0.84

Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease. J Am Coll Cardiol (2017) 0.83

Mitochondrial DNA variants in obesity. PLoS One (2014) 0.83

Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans. PLoS One (2015) 0.83

Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures. J Invest Dermatol (2015) 0.83

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium. Behav Genet (2015) 0.83

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children. Eur Respir J (2016) 0.82

Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes. Eur J Hum Genet (2015) 0.82

Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis. Gut (2015) 0.82

Variation and association to diabetes in 2000 full mtDNA sequences mined from an exome study in a Danish population. Eur J Hum Genet (2014) 0.81

Lymphoblastoid cell lines reveal associations of adult DNA methylation with childhood and current adversity that are distinct from whole blood associations. Int J Epidemiol (2015) 0.81

Sparse Modeling Reveals miRNA Signatures for Diagnostics of Inflammatory Bowel Disease. PLoS One (2015) 0.81

Genome-wide analysis of parent-of-origin effects in non-syndromic orofacial clefts. Eur J Hum Genet (2013) 0.81

Investigation of complement component C4 copy number variation in human longevity. PLoS One (2014) 0.80

Prevalence of Pulmonary Hypertension in the General Population: The Rotterdam Study. PLoS One (2015) 0.80