ArticlemedRxiv : the preprint server for health sciences2025
Gene-environment interaction analysis in atopic eczema: evidence from large population datasets and modelling
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78 authors.
Marie StandlInstitute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Ashley Budu-AggreyMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, UK.
Luke J JohnstonCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, Crewe Road South, University of Edinburgh, Edinburgh, UK.
Martina S EliasCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, Crewe Road South, University of Edinburgh, Edinburgh, UK.
S Hasan ArshadClinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Peter BagerDepartment of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
Veronique BatailleDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Helena BlakewayMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, UK.
Klaus BonnelykkeCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Dorret BoomsmaVrije Universiteit, Department of Biological Psychology Van der Boechorststraat, Amsterdam, The Netherlands.
Ben M BrumptonHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Mariona Bustamante PinedaISGlobal, Institute for Global Health, Barcelona, Spain.
Archie CampbellCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, Crewe Road South, University of Edinburgh, Edinburgh, UK.
John A CurtinDivision of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Anders EliasenCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
João Ps FadistaDepartment of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
Bjarke FeenstraDepartment of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
Trine GernerDepartment of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Carolina Medina GomezDepartment of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
Sarah GroscheMax-Delbrück-Center (MDC) for Molecular Medicine, 13125, Berlin, Germany.
Kristine B GutzkowDepartment of Air Quality and Noise, Division of Climate and Environmental Health, Norwegian Institute of Public Health (NIPH), Oslo, Norway.
Anne-Sofie HallingDepartment of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, build. 4, 2400 Copenhagen N, Denmark.
Caroline HaywardCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, Crewe Road South, University of Edinburgh, Edinburgh, UK.
John HendersonMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, UK.
Esther Herrera-LuisDepartment of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
John W HollowayNIHR Southampton Biomedical Research Centre, University Hospitals Southampton NHS Foundation Trust, Southampton, UK.
Joukejan HottengaVrije Universiteit, Department of Biological Psychology Van der Boechorststraat, Amsterdam, The Netherlands.
Jonathan O'B HourihaneRoyal College of Surgeons in Ireland, Dublin, Ireland.
Chen HuThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Kristian HveemHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Amaia IrizarSpanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Benedicte JacqueminUniv Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France.
Leon JessenCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Sara KressIUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
Ramesh J KurukulaaratchyClinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Susanne LauDepartment of Pediatric Respiratory Medicine, Immunology, and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Sabrina LlopSpanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Mari LøsetHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Ingo MarenholtzMax-Delbrück-Center (MDC) for Molecular Medicine, 13125, Berlin, Germany.
Dan MasonBradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, England, BD9 6RJ, UK.
Daniel L McCartneyCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, Crewe Road South, University of Edinburgh, Edinburgh, UK.
Mads MelbyeDanish Cancer Institute, Copenhagen, Denmark.
Erik MelénDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Camelia MinicaVrije Universiteit, Department of Biological Psychology Van der Boechorststraat, Amsterdam, The Netherlands.
Clare S MurrayDivision of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Tamar NijstenDepartment of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Luba M PardoDepartment of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Suzanne PasmansDepartment of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Craig E PennellSchool of Medicine and Public Health, The University of Newcastle, New South Wales, NSW 2308, Australia.
Maria R RinnovDepartment of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Gillian SantorelliBradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, England, BD9 6RJ, UK.
Tamara SchikowskiIUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
Darina SheehanINFANT Centre, University College Cork, Cork, Ireland.
Angela SimpsonDivision of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Cilla SöderhällDepartment of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Laurent F ThomasHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Jacob P ThyssenDepartment of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, build. 4, 2400 Copenhagen N, Denmark.
Maties TorrentArea de Salut de Menorca, ib-salut, Balearic Islands, Spain.
Toos van BeijsterveldtVrije Universiteit, Department of Biological Psychology Van der Boechorststraat, Amsterdam, The Netherlands.
Alessia ViscontiDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Judith M VonkUniversity of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
Carol A WangSchool of Medicine and Public Health, The University of Newcastle, New South Wales, NSW 2308, Australia.
Cheng-Jian XuCentre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.
Ali H ZiyabDepartment of Community Medicine and Behavioral Sciences, College of Medicine, Kuwait University, Kuwait.
UK Translational Research Network in Dermatology
BIOMAP consortium
Adnan CustovicNational Heart and Lung Institute, Imperial College London, UK.
Paola Di MeglioThe Francis Crick Institute, London, UK.
Liesbeth DuijtsDepartment of Pediatrics, divisions of Respiratory Medicine and Allergology, and Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Carsten FlohrDepartment of Paediatric Dermatology, St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
Alan D IrvineDepartment of Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
Gerard H KoppelmanUniversity of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.
Young-Ae LeeMax-Delbrück-Center (MDC) for Molecular Medicine, 13125, Berlin, Germany.
Nick J ReynoldsTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Catherine SmithSt John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London.
Sinéad M LanganFaculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Lavinia PaternosterMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, UK.
Sara J BrownCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, Crewe Road South, University of Edinburgh, Edinburgh, UK.
Funding
Wellcome Trust
Abstract
Background: Environmental factors play a role in the pathogenesis of complex traits including atopic eczema (AE) and a greater understanding of gene-environment interactions (G*E) is needed to define pathomechanisms for disease prevention. We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors. We tested for replication using a further 10 studies and Results: The discovery analysis showed suggestive evidence for interaction (p<0.05) between 7 environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total (maxN=25,339). In replication analysis (maxN=252,040) dog exposure*rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (OR Conclusions: Interaction analysis and functional assessment provide evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via
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atopic dermatitisAtopic eczemadogenvironmentepidemiologygeneticinteractionsibling
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