Gene–Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies
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Ashley
Budu‐Aggrey
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Luke J
Johnston
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Martina S
Elias
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S Hasan
Arshad
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Peter
Bager
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Veronique
Bataille
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Helena
Blakeway
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Klaus
Bønnelykke
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Dorret
Boomsma
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Ben M
Brumpton
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Mariona
Bustamante Pineda
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Campbell
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John A
Curtin
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Anders
Eliasen
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João PS
Fadista
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Bjarke
Feenstra
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Trine
Gerner
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Carolina
Medina‐Gomez
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Sarah
Grosche
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Kristine B
Gutzkow
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Anne‐Sofie
Halling
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Caroline
Hayward
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John
Henderson
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Esther
Herrera‐Luis
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Holloway
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Joukejan
Hottenga
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Jonathan
O’B Hourihane
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Chen
Hu
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Kristian
Hveem
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Amaia
Irizar
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Jacquemi
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Jessen
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Kress
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Kurukulaaratchy
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Lau
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Llop
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Løset
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Marenholz
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Dan
Mason
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McCartney
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Melbye
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Erik
Melén
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Camelia
Minica
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Clare S
Murray
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Tamar
Nijsten
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Luba M
Pardo
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Suzanne
Pasmans
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Craig E
Pennell
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Maria R
Rinnov
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Gillian
Santorelli
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Tamara
Schikowski
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Darina
Sheehan
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Angela
Simpson
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Cilla
Söderhäll
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Laurent F
Thomas
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Jacob P
Thyssen
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Maties
Torrent
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Toos
van Beijsterveldt
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Alessia
Visconti
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Judith M
Vonk
;
Carol A
Wang
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Cheng‐Jian
Xu
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Ali H
Ziyab
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Adnan
Custovic
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Paola
Di Meglio
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Liesbeth
Duijts
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Carsten
Flohr
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Alan D
Irvine
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Gerard H
Koppelman
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Young‐Ae
Lee
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Nick J
Reynolds
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Catherine
Smith
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Sinéad M
Langan
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Lavinia
Paternoster
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Sara J
Brown
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(2025)
Gene–Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies.
Allergy.
pp. 1-12.
ISSN 0105-4538
DOI: 10.1111/all.16605
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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