Journal article
Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis
Nature genetics, Vol.44(2), pp.187-192
02/2012
DOI: 10.1038/ng.1017
PMCID: PMC3272375
PMID: 22197932
Abstract
Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10−13) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10−9), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10−8). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.
Details
- Title: Subtitle
- Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis
- Creators
- Lavinia Paternoster - MRC CAiTE centre, School of Social & Community Medicine, University of Bristol, Bristol, UKMarie Standl - Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyChih-Mei Chen - Hannover Medical School, Department for Paediatric Pneumology, Allergy and Neonatology, Hannover, GermanyAdaikalavan Ramasamy - Respiratory Epidemiology and Public Health, Imperial College London, United KingdomKlaus Bønnelykke - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood; Health Sciences, University of Copenhagen & Copenhagen University Hospital, Gentofte, DenmarkLiesbeth Duijts - The Generation R Study Group, Erasmus Medical Center, Rotterdam, The NetherlandsManuel A Ferreira - Queensland Institute of Medical Research, Brisbane, AustraliaAlexessander Couto Alves - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United KingdomJacob P Thyssen - National Allergy Research Centre, Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, DenmarkEva Albrecht - Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyHansjörg Baurecht - Department of Dermatology and Allergy, Technische Universität München, Munich, GermanyBjarke Feenstra - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkPatrick MA Sleiman - The Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USAPirro Hysi - Department of Twin Research and Genetic Epidemiology, King’s College LondonNicole M Warrington - School of Women’s and Infants’ Health, The University of Western Australia, Western Australia, AustraliaIvan Curjuric - Swiss Tropical and Public Health Institute (SwissTPH), Basel, SwitzerlandRonny Myhre - Norwegian Institute of Public Health, Department of Genes and Environment, Division of Epidemiology, Oslo, NorwayJohn A Curtin - The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, UKMaria M Groen-Blokhuis - Department of Biological Psychology, VU University, Amsterdam, The NetherlandsMarjan Kerkhof - Department of Pediatric Pulmonology and Allergology, University Medical Center Groningen, University of Groningen, GRIAC research institute, Groningen, The NetherlandsAnnika Sääf - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenAndre Franke - Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, GermanyDavid Ellinghaus - Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, GermanyRegina Fölster-Holst - Department of Dermatology, Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, GermanyEmmanouil Dermitzakis - Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, 1211 SwitzerlandStephen B Montgomery - Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, 1211 SwitzerlandHolger Prokisch - Institute of Human Genetics, Technische Universität München, Munich, GermanyKatharina Heim - Institute of Human Genetics, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, GermanyAnna-Liisa Hartikainen - Department of Obstetrics and Gynaecology, University of OuluAnneli Pouta - Department of Obstetrics and Gynaecology, University of OuluJuha Pekkanen - Department of Environmental Health, National Institute for Health and Welfare (THL), Kuopio, FinlandAlexandra IF Blakemore - School of Public Health, Imperial College LondonJessica L Buxton - School of Public Health, Imperial College LondonMarika Kaakinen - Institute of Health Sciences, University of Oulu, Oulu, Finland Biocenter Oulu, University of Oulu, Oulu, FinlandDavid L Duffy - Queensland Institute of Medical Research, Brisbane, AustraliaPamela A Madden - Washington University School of Medicine, St Louis, United StatesAndrew C Heath - Washington University School of Medicine, St Louis, United StatesGrant W Montgomery - Queensland Institute of Medical Research, Brisbane, AustraliaPhilip J Thompson - Lung Institute of Western Australia (WA) and Centre for Asthma, Allergy and Respiratory Research, University of WA, Perth, AustraliaMelanie C Matheson - Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, AustraliaPeter Le Souëf - School of Paediatrics and Child Health, Princess Margaret Hospital for Children, Perth, AustraliaBeate St Pourcain - The School of Social & Community Medicine, University of Bristol, Bristol, UKGeorge Davey Smith - MRC CAiTE centre, School of Social & Community Medicine, University of Bristol, Bristol, UKJohn Henderson - The School of Social & Community Medicine, University of Bristol, Bristol, UKJohn P Kemp - MRC CAiTE centre, School of Social & Community Medicine, University of Bristol, Bristol, UKNicholas J Timpson - MRC CAiTE centre, School of Social & Community Medicine, University of Bristol, Bristol, UKPanos Deloukas - Wellcome Trust Sanger Institute, Cambridge, United KingdomSusan M Ring - The School of Social & Community Medicine, University of Bristol, Bristol, UKH-Erich Wichmann - Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyMartina Müller-Nurasyid - Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyNatalija Novak - Department of Dermatology and Allergy, University of Bonn Medical Center, Bonn, GermanyNorman Klopp - Unit for Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyElke Rodríguez - Department of Dermatology and Allergy, Technische Universität München, Munich, GermanyWendy McArdle - University of Bristol, ALSPAC Laboratory, School of Social & Community Medicine, University of Bristol, Bristol, UKAllan Linneberg - Research Center for Prevention and Health, Glostrup University Hospital, DenmarkTorkil Menné - National Allergy Research Centre, Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, DenmarkEllen A Nohr - Institute of Public Health, Aarhus University, DenmarkAlbert Hofman - The Generation R Study Group, Erasmus Medical Center, Rotterdam, The NetherlandsAndré G Uitterlinden - The Generation R Study Group, Erasmus Medical Center, Rotterdam, The NetherlandsCornélia M van Duijn - Department of Epidemiology, Erasmus Medical Center, Rotterdam, The NetherlandsFernando Rivadeneira - The Generation R Study Group, Erasmus Medical Center, Rotterdam, The NetherlandsJohan C de Jongste - Department of Pediatrics, Division of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The NetherlandsRalf JP van der Valk - The Generation R Study Group, Erasmus Medical Center, Rotterdam, The NetherlandsMatthias Wjst - Comprehensive Pneumology Center and Institute of Lung Biology and Disease, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyRain Jogi - Lung Clinic, Tartu University, Tartu, EstoniaFrank Geller - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkHeather A Boyd - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkJeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, USACecilia Kim - The Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USAFrank Mentch - The Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USAMichael March - The Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USAMassimo Mangino - Department of Twin Research and Genetic Epidemiology, King’s College LondonTim D Spector - Department of Twin Research and Genetic Epidemiology, King’s College LondonVeronique Bataille - Department of Twin Research and Genetic Epidemiology, King’s College LondonCraig E Pennell - School of Women’s and Infants’ Health, The University of Western Australia, Western Australia, AustraliaPatrick G Holt - Telethon Institute for Child Health Research and Centre for Child Health Research, The University of Western Australia, Western Australia, AustraliaPeter Sly - Queensland Children’s Medical Research Institute; University of Queensland; WHO Collaborating Centre for Research on Children’s Environmental Health, Queensland, AustraliaCarla MT Tiesler - Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyElisabeth Thiering - Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyThomas Illig - Unit for Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyMedea Imboden - Swiss Tropical and Public Health Institute (SwissTPH), Basel, SwitzerlandWenche Nystad - Norwegian Institute of Public Health, Division of Epidemiology, Oslo, NorwayAngela Simpson - The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, UKJouke-Jan Hottenga - Department of Biological Psychology, VU University, Amsterdam, The NetherlandsDirkje Postma - Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsGerard H Koppelman - Dpt of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children ’s Hospital, GRIAC research institute, University Medical Center Groningen, University of Groningen, The NetherlandsHenriette A Smit - Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The NetherlandsCilla Söderhäll - Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, SwedenBo Chawes - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood; Health Sciences, University of Copenhagen & Copenhagen University Hospital, Gentofte, DenmarkEskil Kreiner-Møller - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood; Health Sciences, University of Copenhagen & Copenhagen University Hospital, Gentofte, DenmarkHans Bisgaard - COPSAC, Copenhagen Prospective Studies on Asthma in Childhood; Health Sciences, University of Copenhagen & Copenhagen University Hospital, Gentofte, DenmarkErik Melén - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenDorret I Boomsma - Department of Biological Psychology, VU University, Amsterdam, The NetherlandsAdnan Custovic - The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, UKBo Jacobsson - Norwegian Institute of Public Health, Department of Genes and Environment, Division of Epidemiology, Oslo, NorwayNicole M Probst-Hensch - Swiss Tropical and Public Health Institute (SwissTPH), Basel, SwitzerlandLyle J Palmer - Ontario Institute for Cancer Research, Toronto; University of Toronto, Toronto, CanadaDaniel Glass - Department of Twin Research and Genetic Epidemiology, King’s College LondonHakon Hakonarson - The Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USAMads Melbye - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkDeborah L Jarvis - Respiratory Epidemiology and Public Health, Imperial College London, United KingdomVincent WV Jaddoe - The Generation R Study Group, Erasmus Medical Center, Rotterdam, The NetherlandsChristian Gieger - Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyDavid P Strachan - Division of Population Health Sciences and Education, St George’s, University of London, London, UKNicholas G Martin - Queensland Institute of Medical Research, Brisbane, AustraliaMarjo-Riitta Jarvelin - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United KingdomJoachim Heinrich - Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, GermanyDavid M Evans - MRC CAiTE centre, School of Social & Community Medicine, University of Bristol, Bristol, UKStephan Weidinger - Department of Dermatology, Allergology, and Venerology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.44(2), pp.187-192
- DOI
- 10.1038/ng.1017
- PMID
- 22197932
- PMCID
- PMC3272375
- NLM abbreviation
- Nat Genet
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Grant note
- 068545 || WT / Wellcome Trust : G9815508(74882) || MRC_ / Medical Research Council : G0800582(86758) || MRC_ / Medical Research Council : G0601361(80219) || MRC_ / Medical Research Council : 092731 || WT / Wellcome Trust : 084762 || WT / Wellcome Trust : 076467 || WT / Wellcome Trust :
- Language
- English
- Date published
- 02/2012
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025337602771
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