Marie Standl, Ashley Budu-Aggrey, Luke J. Johnston, Martina S. Elias, S. Hasan Arshad, Peter Bager, Veronique Bataille, Helena Blakeway, Klaus Bønnelykke, Dorret Boomsma, Ben M. Brumpton, Mariona Bustamante Pineda, Archie Campbell, John A. Curtin, Anders Eliasen, João P. S. Fadista, Bjarke Feenstra, Trine Gerner, Carolina Medina-Gomez, Sarah Grosche, Kristine B. Gutzkow, Anne-Sofie Halling, Caroline Hayward, John Henderson, Esther Herrera-Luis, John W. Holloway, Joukejan Hottenga, Jonathan O’B Hourihane, Chen Hu, Kristian Hveem, Amaia Irizar, Bénédicte Jacquemin, Leon Jessen, Sara Kress, Ramesh J. Kurukulaaratchy, Susanne Lau, Sabrina Llop, Mari Løset, Ingo Marenholz, Dan Mason, Daniel L. McCartney, Mads Melbye, Erik Melén, Camelia Minica, Clare S. Murray, Tamar Nijsten, Luba M. Pardo, Suzanne Pasmans, Craig E. Pennell, Maria R. Rinnov, Gillian Santorelli, Tamara Schikowski, Darina Sheehan, Angela Simpson, Cilla Söderhäll, Laurent F. Thomas, Jacob P. Thyssen, Maties Torrent, Toos van Beijsterveldt, Alessia Visconti, Judith M. Vonk, Carol A. Wang, Cheng-Jian Xu, Ali H. Ziyab, UK Translational Research Network in Dermatology, BIOMAP Consortium, Adnan Custovic, Paola Di Meglio, Liesbeth Duijts, Carsten Flohr, Alan D. Irvine, Gerard H. Koppelman, Young-Ae Lee, Nick J. Reynolds, Catherine Smith, Sinéad M. Langan, Lavinia Paternoster, Sara J. Brown
{"title":"基因-环境相互作用影响特应性湿疹的风险：人群和体外研究。","authors":"Marie Standl, Ashley Budu-Aggrey, Luke J. Johnston, Martina S. Elias, S. Hasan Arshad, Peter Bager, Veronique Bataille, Helena Blakeway, Klaus Bønnelykke, Dorret Boomsma, Ben M. Brumpton, Mariona Bustamante Pineda, Archie Campbell, John A. Curtin, Anders Eliasen, João P. S. Fadista, Bjarke Feenstra, Trine Gerner, Carolina Medina-Gomez, Sarah Grosche, Kristine B. Gutzkow, Anne-Sofie Halling, Caroline Hayward, John Henderson, Esther Herrera-Luis, John W. Holloway, Joukejan Hottenga, Jonathan O’B Hourihane, Chen Hu, Kristian Hveem, Amaia Irizar, Bénédicte Jacquemin, Leon Jessen, Sara Kress, Ramesh J. Kurukulaaratchy, Susanne Lau, Sabrina Llop, Mari Løset, Ingo Marenholz, Dan Mason, Daniel L. McCartney, Mads Melbye, Erik Melén, Camelia Minica, Clare S. Murray, Tamar Nijsten, Luba M. Pardo, Suzanne Pasmans, Craig E. Pennell, Maria R. Rinnov, Gillian Santorelli, Tamara Schikowski, Darina Sheehan, Angela Simpson, Cilla Söderhäll, Laurent F. Thomas, Jacob P. Thyssen, Maties Torrent, Toos van Beijsterveldt, Alessia Visconti, Judith M. Vonk, Carol A. Wang, Cheng-Jian Xu, Ali H. Ziyab, UK Translational Research Network in Dermatology, BIOMAP Consortium, Adnan Custovic, Paola Di Meglio, Liesbeth Duijts, Carsten Flohr, Alan D. Irvine, Gerard H. Koppelman, Young-Ae Lee, Nick J. Reynolds, Catherine Smith, Sinéad M. Langan, Lavinia Paternoster, Sara J. Brown","doi":"10.1111/all.16605","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The discovery analysis (including 25,339 individuals) showed suggestive evidence for interaction (<i>p</i> < 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 <i>IL7R</i>) was nominally significant (OR<sub>interaction</sub> = 0.91 [0.83–0.99] <i>p</i> = 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<sub>interaction</sub> = 0.84 [0.75–0.94] <i>p</i> = 0.003), but replication analysis was under-powered (OR<sub>interaction</sub> = 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.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Interaction analysis and functional assessment provide preliminary evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via <i>IL7R</i>, 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.</p>\n </section>\n </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 8","pages":"2201-2212"},"PeriodicalIF":12.0000,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16605","citationCount":"0","resultStr":"{\"title\":\"Gene–Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies\",\"authors\":\"Marie Standl, Ashley Budu-Aggrey, Luke J. Johnston, Martina S. Elias, S. Hasan Arshad, Peter Bager, Veronique Bataille, Helena Blakeway, Klaus Bønnelykke, Dorret Boomsma, Ben M. Brumpton, Mariona Bustamante Pineda, Archie Campbell, John A. Curtin, Anders Eliasen, João P. S. Fadista, Bjarke Feenstra, Trine Gerner, Carolina Medina-Gomez, Sarah Grosche, Kristine B. Gutzkow, Anne-Sofie Halling, Caroline Hayward, John Henderson, Esther Herrera-Luis, John W. Holloway, Joukejan Hottenga, Jonathan O’B Hourihane, Chen Hu, Kristian Hveem, Amaia Irizar, Bénédicte Jacquemin, Leon Jessen, Sara Kress, Ramesh J. Kurukulaaratchy, Susanne Lau, Sabrina Llop, Mari Løset, Ingo Marenholz, Dan Mason, Daniel L. McCartney, Mads Melbye, Erik Melén, Camelia Minica, Clare S. Murray, Tamar Nijsten, Luba M. Pardo, Suzanne Pasmans, Craig E. Pennell, Maria R. Rinnov, Gillian Santorelli, Tamara Schikowski, Darina Sheehan, Angela Simpson, Cilla Söderhäll, Laurent F. Thomas, Jacob P. Thyssen, Maties Torrent, Toos van Beijsterveldt, Alessia Visconti, Judith M. Vonk, Carol A. Wang, Cheng-Jian Xu, Ali H. Ziyab, UK Translational Research Network in Dermatology, BIOMAP Consortium, Adnan Custovic, Paola Di Meglio, Liesbeth Duijts, Carsten Flohr, Alan D. Irvine, Gerard H. Koppelman, Young-Ae Lee, Nick J. Reynolds, Catherine Smith, Sinéad M. Langan, Lavinia Paternoster, Sara J. Brown\",\"doi\":\"10.1111/all.16605\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The discovery analysis (including 25,339 individuals) showed suggestive evidence for interaction (<i>p</i> < 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 <i>IL7R</i>) was nominally significant (OR<sub>interaction</sub> = 0.91 [0.83–0.99] <i>p</i> = 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<sub>interaction</sub> = 0.84 [0.75–0.94] <i>p</i> = 0.003), but replication analysis was under-powered (OR<sub>interaction</sub> = 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Interaction analysis and functional assessment provide preliminary evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via <i>IL7R</i>, supporting observational epidemiology showing a protective effect for dog ownership. 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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 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.
期刊介绍：
Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality.
Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.
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