Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies
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 betw...
| Autores: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Tipo de documento: | Artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Conselleria de Salut i Consum del Govern de les Illes Balears |
| Repositorio: | Docusalut |
| Lenguaje: | Inglés |
| OAI Identifier: | oai:docusalut.com:20.500.13003/25873 |
| Acceso en línea: | https://hdl.handle.net/20.500.13003/25873 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Dermatitis, Atopic Dogs Environment Genes Interaction Dermatitis Atópica Perros Ambiente Interacción Bastón-Cono atopic eczema dog environment gene interaction |
| _version_ | 1878732930675638272 |
|---|---|
| author | Standl, Marie |
| author2 | Budu-Aggrey, Ashley Johnston, Luke J Elias, Martina S Arshad, S Hasan Bager, Peter Bataille, Veronique Blakeway, Helena Bønnelykke, Klaus Boomsma, Dorret Brumpton, Ben M Bustamante Pineda, Mariona Campbell, Archie Curtin, John A Eliasen, Anders Fadista, João P S Feenstra, Bjarke Gerner, Trine Medina-Gomez, Carolina Grosche, Sarah Gutzkow, Kristine B Halling, Anne-Sofie Hayward, Caroline Henderson, John Herrera-Luis, Esther Holloway, John W Hottenga, Joukejan O'B Hourihane, Jonathan Hu, Chen Hveem, Kristian Irizar, Amaia Jacquemin, Bénédicte Jessen, Leon Kress, Sara Kurukulaaratchy, Ramesh J Lau, Susanne Llop, Sabrina Løset, Mari Marenholz, Ingo Mason, Dan McCartney, Daniel L Melbye, Mads Melén, Erik Minica, Camelia Murray, Clare S Nijsten, Tamar Pardo, Luba M Pasmans, Suzanne Pennell, Craig E Rinnov, Maria R Santorelli, Gillian Schikowski, Tamara Sheehan, Darina Simpson, Angela Söderhäll, Cilla Thomas, Laurent F Thyssen, Jacob P Torrent Quetglas, Maties van Beijsterveldt, Toos Visconti, Alessia Vonk, Judith M Wang, Carol A Xu, Cheng-Jian Ziyab, Ali H Custovic, Adnan Di Meglio, Paola Duijts, Liesbeth Flohr, Carsten Irvine, Alan D Koppelman, Gerard H Lee, Young-Ae Reynolds, Nick J Smith, Catherine Langan, Sinéad M Paternoster, Lavinia Brown, Sara J |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| author_browse | Arshad, S Hasan Bager, Peter Bataille, Veronique Blakeway, Helena Boomsma, Dorret Brown, Sara J Brumpton, Ben M Budu-Aggrey, Ashley Bustamante Pineda, Mariona Bønnelykke, Klaus Campbell, Archie Curtin, John A Custovic, Adnan Di Meglio, Paola Duijts, Liesbeth Elias, Martina S Eliasen, Anders Fadista, João P S Feenstra, Bjarke Flohr, Carsten Gerner, Trine Grosche, Sarah Gutzkow, Kristine B Halling, Anne-Sofie Hayward, Caroline Henderson, John Herrera-Luis, Esther Holloway, John W Hottenga, Joukejan Hu, Chen Hveem, Kristian Irizar, Amaia Irvine, Alan D Jacquemin, Bénédicte Jessen, Leon Johnston, Luke J Koppelman, Gerard H Kress, Sara Kurukulaaratchy, Ramesh J Langan, Sinéad M Lau, Susanne Lee, Young-Ae Llop, Sabrina Løset, Mari Marenholz, Ingo Mason, Dan McCartney, Daniel L Medina-Gomez, Carolina Melbye, Mads Melén, Erik Minica, Camelia Murray, Clare S Nijsten, Tamar O'B Hourihane, Jonathan Pardo, Luba M Pasmans, Suzanne Paternoster, Lavinia Pennell, Craig E Reynolds, Nick J Rinnov, Maria R Santorelli, Gillian Schikowski, Tamara Sheehan, Darina Simpson, Angela Smith, Catherine Standl, Marie Söderhäll, Cilla Thomas, Laurent F Thyssen, Jacob P Torrent Quetglas, Maties Visconti, Alessia Vonk, Judith M Wang, Carol A Xu, Cheng-Jian Ziyab, Ali H van Beijsterveldt, Toos |
| author_facet | Standl, Marie Budu-Aggrey, Ashley Johnston, Luke J Elias, Martina S Arshad, S Hasan Bager, Peter Bataille, Veronique Blakeway, Helena Bønnelykke, Klaus Boomsma, Dorret Brumpton, Ben M Bustamante Pineda, Mariona Campbell, Archie Curtin, John A Eliasen, Anders Fadista, João P S Feenstra, Bjarke Gerner, Trine Medina-Gomez, Carolina Grosche, Sarah Gutzkow, Kristine B Halling, Anne-Sofie Hayward, Caroline Henderson, John Herrera-Luis, Esther Holloway, John W Hottenga, Joukejan O'B Hourihane, Jonathan Hu, Chen Hveem, Kristian Irizar, Amaia Jacquemin, Bénédicte Jessen, Leon Kress, Sara Kurukulaaratchy, Ramesh J Lau, Susanne Llop, Sabrina Løset, Mari Marenholz, Ingo Mason, Dan McCartney, Daniel L Melbye, Mads Melén, Erik Minica, Camelia Murray, Clare S Nijsten, Tamar Pardo, Luba M Pasmans, Suzanne Pennell, Craig E Rinnov, Maria R Santorelli, Gillian Schikowski, Tamara Sheehan, Darina Simpson, Angela Söderhäll, Cilla Thomas, Laurent F Thyssen, Jacob P Torrent Quetglas, Maties van Beijsterveldt, Toos Visconti, Alessia Vonk, Judith M Wang, Carol A Xu, Cheng-Jian Ziyab, Ali H Custovic, Adnan Di Meglio, Paola Duijts, Liesbeth Flohr, Carsten Irvine, Alan D Koppelman, Gerard H Lee, Young-Ae Reynolds, Nick J Smith, Catherine Langan, Sinéad M Paternoster, Lavinia Brown, Sara J |
| author_role | author |
| collection | Docusalut |
| description | 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 (OR = 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 (OR = 0.84 [0.75-0.94] p = 0.003), but replication analysis was under-powered (OR = 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_4cb08e7aca3fe0e6ec3a2d112e558c3e |
| institution | Conselleria de Salut i Consum del Govern de les Illes Balears |
| instname_str | Conselleria de Salut i Consum del Govern de les Illes Balears |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:docusalut.com:20.500.13003/25873 |
| publishDate | 2025 |
| publishDateSort | 2025 |
| publisher | Wiley |
| publisherStr | Wiley |
| reponame_str | Docusalut |
| spelling | Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies Standl, Marie Budu-Aggrey, Ashley Johnston, Luke J Elias, Martina S Arshad, S Hasan Bager, Peter Bataille, Veronique Blakeway, Helena Bønnelykke, Klaus Boomsma, Dorret Brumpton, Ben M Bustamante Pineda, Mariona Campbell, Archie Curtin, John A Eliasen, Anders Fadista, João P S Feenstra, Bjarke Gerner, Trine Medina-Gomez, Carolina Grosche, Sarah Gutzkow, Kristine B Halling, Anne-Sofie Hayward, Caroline Henderson, John Herrera-Luis, Esther Holloway, John W Hottenga, Joukejan O'B Hourihane, Jonathan Hu, Chen Hveem, Kristian Irizar, Amaia Jacquemin, Bénédicte Jessen, Leon Kress, Sara Kurukulaaratchy, Ramesh J Lau, Susanne Llop, Sabrina Løset, Mari Marenholz, Ingo Mason, Dan McCartney, Daniel L Melbye, Mads Melén, Erik Minica, Camelia Murray, Clare S Nijsten, Tamar Pardo, Luba M Pasmans, Suzanne Pennell, Craig E Rinnov, Maria R Santorelli, Gillian Schikowski, Tamara Sheehan, Darina Simpson, Angela Söderhäll, Cilla Thomas, Laurent F Thyssen, Jacob P Torrent Quetglas, Maties van Beijsterveldt, Toos Visconti, Alessia Vonk, Judith M Wang, Carol A Xu, Cheng-Jian Ziyab, Ali H Custovic, Adnan Di Meglio, Paola Duijts, Liesbeth Flohr, Carsten Irvine, Alan D Koppelman, Gerard H Lee, Young-Ae Reynolds, Nick J Smith, Catherine Langan, Sinéad M Paternoster, Lavinia Brown, Sara J Dermatitis, Atopic Dogs Environment Genes Interaction Dermatitis Atópica Perros Ambiente Interacción Bastón-Cono atopic eczema dog environment gene interaction 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 (OR = 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 (OR = 0.84 [0.75-0.94] p = 0.003), but replication analysis was under-powered (OR = 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. Wiley https://hdl.handle.net/20.500.13003/25873 |
| spellingShingle | Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies Standl, Marie Dermatitis, Atopic Dogs Environment Genes Interaction Dermatitis Atópica Perros Ambiente Interacción Bastón-Cono atopic eczema dog environment gene interaction |
| title | Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies |
| title_full | Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies |
| title_fullStr | Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies |
| title_full_unstemmed | Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies |
| title_short | Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies |
| title_sort | Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies |
| topic | Dermatitis, Atopic Dogs Environment Genes Interaction Dermatitis Atópica Perros Ambiente Interacción Bastón-Cono atopic eczema dog environment gene interaction |
| topic_facet | Dermatitis, Atopic Dogs Environment Genes Interaction Dermatitis Atópica Perros Ambiente Interacción Bastón-Cono atopic eczema dog environment gene interaction |
| url | https://hdl.handle.net/20.500.13003/25873 |