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Standl, M. ; Budu-Aggrey, A.* ; Johnston, L.J.* ; Elias, M.S.* ; Arshad, S.H.* ; Bager, P.* ; Bataille, V.* ; Blakeway, H.* ; Bønnelykke, K.* ; Boomsma, D.* ; Brumpton, B.M.* ; Bustamante Pineda, M.* ; Campbell, A.* ; Curtin, J.A.* ; Eliasen, A.U.* ; Fadista, J.P.S.* ; Feenstra, B.* ; Gerner, T.* ; Medina-Gomez, C.* ; Grosche, S.* ; Gutzkow, K.B.* ; Halling, A.S.* ; Hayward, C.* ; Henderson, J.* ; Herrera-Luis, E.* ; Holloway, J.W.* ; Hottenga, J.* ; O'B Hourihane, J.* ; Hu, C.* ; Hveem, K.* ; Irizar, A.* ; Jacquemi, B.* ; Jessen, L.E.* ; Kress, S.* ; Kurukulaaratchy, R.J.* ; Lau, S.* ; Llop, S.* ; Løset, M.* ; Marenholz, I.* ; Mason, D.* ; McCartney, D.L.* ; Melbye, M.* ; Melén, E.* ; Minica, C.C.* ; Murray, C.S.* ; Nijsten, T.* ; Pardo, L.M.* ; Pasmans, S.G.M.A.* ; Pennell, C.E.* ; Rinnov, M.R.* ; Santorelli, G.* ; Schikowski, T.* ; Sheehan, D.* ; Simpson, A.* ; Söderhäll, C.* ; Thomas, L.F.* ; Thyssen, J.P.* ; Torrent, M.* ; van Beijsterveldt, T.* ; Visconti, A.* ; Vonk, J.M.* ; Wang, C.A.* ; Xu, C.J.* ; Ziyab, A.H.* ; Custovic, A.* ; Di Meglio, P.* ; Duijts, L.* ; Flohr, C.* ; Irvine, A.D.* ; Koppelman, G.H.* ; Lee, Y.A.* ; Reynolds, N.J.* ; Smith, C.* ; Langan, S.M.* ; Paternoster, L.* ; Brown, S.J.*

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

Allergy, DOI: 10.1111/all.16605 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Atopic Eczema ; Dog ; Environment ; Gene ; Interaction; Genome-wide Association; Dermatitis; Mutations; Allergy; Asthma
ISSN (print) / ISBN 0105-4538
e-ISSN 1398-9995
Journal Allergy
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Grants Netherlands Ministry of Health, Welfare, and Sport
Wellcome Trust
German Federal Ministry of Education and Research
Innovative Medicines Initiative
European Research Council
National Institute for Health and Care Research
BMA James Trust
The JP Moulton Charitable Foundation
The North West Lung Centre Charity
Netherlands Organization for Health Research and Development
Ministerio de Ciencia e Innovación
European Science Foundation
Asthma and Lung UK
Netherlands Organization for Scientific Research
Lung Foundation Netherlands
Netherlands Ministry of Spatial Planning, Housing, and the Environment
Medical Research Council