Gene-environment interaction affects risk of atopic eczema: Population and in vitro studies

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• dc.contributor.author Standl, Marie
• dc.contributor.author Bustamante Pineda, Mariona
• dc.contributor.author Brown, Sara J.
• dc.date.accessioned 2025-07-31T07:20:23Z
• dc.date.available 2025-07-31T07:20:23Z
• dc.date.issued 2025
• dc.description Data de publicació electrònica: 04-06-2025
• dc.description.abstract Background: Multiple environmental and genetic factors play a role in the pathogenesis of atopic eczema (AE). We aimed to investigate gene-environment interactions (G × E) to improve understanding of the pathophysiology. Methods: 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 in vitro modeling to independently assess findings. Results: The discovery analysis (including 25,339 individuals) showed suggestive evidence for interaction (p < 0.05) between seven 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. In the replication analysis (254,532 individuals) dog exposure × rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (ORinteraction = 0.91 [0.83-0.99] p = 0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (ORinteraction = 0.84 [0.75-0.94] p = 0.003), but replication analysis was under-powered (ORinteraction = 1.09 [0.82-1.46]). rs10214237 homozygous risk genotype is associated with lower IL-7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype. Conclusion: Interaction analysis and functional assessment provide preliminary evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R, supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G × E studied here implies only weak effects are likely to occur.
• dc.description.sponsorship This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under Grant agreement no. 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication/dissemination reflects only the author's view and the JU is not responsible for any use that may be made of the information it contains. M.S. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant agreement no. 949906). N.J.R.'s research/laboratory is funded in part by the Newcastle NIHR Biomedical Research Centre (BRC), the Newcastle NIHR Medtech and In vitro diagnostics co-operative, and the NIHR Newcastle Patient Safety Research Collaboration, and N.J.R. is a NIHR Senior Investigator. L.P. has received funding from a MRC Population Health Scientist Fellowship (MR/J012165/1) and receives support from the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/1, MC_UU_00032/1). S.J.B. holds a Wellcome Trust Senior Research Fellowship (220875/Z/20/Z). The MAS study up to adolescence was funded by several grants from the German Federal Ministry of Education and Research (07015633, 07 ALE 27, 01EE9405/5 and 01EE9406). E.H.-L. was supported by a fellowship awarded by MCIN/AEI/ 10.13039/501100011033 and by ‘ESF Investing in your future’ [PRE2018-083837]. MAAS was supported by the Asthma UK Grants no. 301 (1995–1998), no. 362 (1998–2001), no. 01/012 (2001–2004), No 04/014 (2004–2007), BMA James Trust (2005) and The JP Moulton Charitable Foundation (2004-current), The North west Lung Centre Charity (1997–current) and the Medical Research Council (MRC) G0601361 (2007–2012), MR/K002449/1 (2013–2014) and MR/L012693/1 (2014–2018) and MR/S025340/1 UNICORN (Unified Cohorts Research Network): Disaggregating asthma (2020–2024). This study was delivered through the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre (BRC) (NIHR203308). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The PIAMA study has been supported by project grants from the Netherlands Organisation for Health Research and Development; the Netherlands Organisation for Scientific Research; the Lung Foundation Netherlands (formerly Netherlands Asthma Fund); the Netherlands Ministry of Spatial Planning, Housing, and the Environment; and the Netherlands Ministry of Health, Welfare and Sport. CS is a NIHR Senior Investigator.
• dc.format.mimetype application/pdf
• dc.identifier.citation Standl M, Budu-Aggrey A, Johnston LJ, Elias MS, Arshad SH, Bager P, et al. Gene-environment interaction affects risk of atopic eczema: Population and in vitro studies. Allergy. 2025 Jun 4. DOI: 10.1111/all.16605
• dc.identifier.doi http://dx.doi.org/10.1111/all.16605
• dc.identifier.issn 0105-4538
• dc.identifier.uri http://hdl.handle.net/10230/71045
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Allergy. 2025 Jun 4
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/821511
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/949906
• dc.rights © 2025 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Atopic eczema
• dc.subject.keyword Dog
• dc.subject.keyword Environment
• dc.subject.keyword Gene
• dc.subject.keyword Interaction
• dc.title Gene-environment interaction affects risk of atopic eczema: Population and in vitro studies
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion