The impact of environmental exposures on DNA methylation in the EXPANSE project

作者：Megi Vogli, Ayoung Jeong, Zhebin Yu, Judith M. Vonk, Dorina Ibi, Jaanika Kronberg, Petr Gregor, Lisa Maier, Miriam Leskien, Marta Cirach, Payam Dadvand, Ondřej Mikeš, Olena Gruzieva, Ulrike Gehring, Kathrin Wolf, Mélanie Waldenberger, Medea Imboden, Pavel Čupr, Kees de Hoogh, Gerard H. Koppelman, Erik Melén, Regina Pickford, Elisabeth Thiering, Marie Standl, Apolline Saucy, Cathryn Tonne, Cristina O'Callaghan, Manolis Kogevinas, Mark Nieuwenhuijsen, Marta Cirach, Natalia Ortega, Payam Dadvand, Sergio Olmos, Erik Melén, Douglas I. Walker, Joline W. J. Beulens, Maria Gabriela Matias de Pinho, Joreintje D. Mackenbach, Licia Iacoviello, Daniela Porta, Federica Asta, Martina Culasso, Massimo Stafoggia, G. Ardine de Wit, Tabea Sonnenschein, Simon Scheider, Karin Jongsma, Annelien L. Bredenoord, Caspar Willem Safarlou, Anna Oudin, Bertil Forsberg, David Olsson, Matteo Bottai, Craig E. Wheelock, Jaanika Kronberg, Tarmo Annilo, Tõnu Esko, R Luigies, R Tieben, Anna Carreras, Rafael de Cid, Beatriz Cortés, Mireia Obón, Barbara Bodinier, Dragana Vuckovic, Dušan Petrović, Jennifer K Quint, Marc Chadeau‐Hyam, M. L. Whitaker, Paolo Vineis, Sarah Filippi, Sonia Dagninio, Thomas Wright, Verena Zuber, Anna Bergström, Göran Pershagen, Olena Gruzieva, Petter Ljungman, Shizhen He, Hynek Pikhart, Martin Bobák, Alexandra Schneider, Annette Peters, Kathrin Wolf, Marie Standl, Regina Pickford, Susanne Breitner, Tianyu Zhao, Mélanie Waldenberger, Augustin Scalbert, Inge Huybrechts, Marc Gunter, Pekka Keski‐Rahkonen, Reza M. Salek, Jana Klánová, Lenka Andrýsková, Ondřej Mikeš, Pavel Čupr, Pavel Piler, Richard Hůlek, Zdenka Dudová, Nicole Janssen, Alonso Bussalleu, Ayoung Jeong, Benjamin Flückiger, Danielle Vienneau, Dirk Keidel, Emmanuel Schaffner, Gianfranco Lovison, Ikenna C. Eze, Kees de Hoogh, Marek Kwiatkowski, Medea Imboden, Nicole Probst‐Hensch, Cyrille Delpierre, Marine Maurel, Michelle Kelly‐Irving, Raphaële Castagné, Benoît Lepage, Evangelia Samoli, Klea Katsouyanni, Konstantina Dimakopoulou, Sophia Rodopoulou, Maria‐Iosifina Kasdagli, Dimitris Evangelopoulos, Anke Huss, Esmeralda Krop, Gerard Hoek, Jelle Vlaanderen, Jingxian You, Jules Kerckhoffs, Kalliopi Kyriakou, Lützen Portengen, Martje Ebberink, Roel Vermeulen, Ulrike Gehring, Youchen Shen, Zhendong Yuan, Jeroen Lakerveld, Alessandro Gialluisi, Gary W. Miller, Jurriaan van Rijswijk, Simona Costanzo, Werner Rutten, Marta Mańczuk, Paweł Koczkodaj, Agata Ciuba, Kinga Polańska, Wojciech Hanke, Agnieszka Jankowska, Agnieszka Pac, Elżbieta Sochacka-Tatara, Renata Majewska, Jana Klánová, Jelle Vlaanderen, Roel Vermeulen, Nicole Probst‐Hensch, Annette Peters · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.106084 · 被引用次数：2 · 研究领域：Epigenetics and DNA Methylation、Chemical Reactions and Isotopes、Per- and polyfluoroalkyl substances research

Background Living in an urban environment exposes the population to a mix of environmental and social factors, known as the Urban Exposome, that can influence health via changes in DNA methylation. We hypothesised that linking urban exposures with epigenome-wide DNA methylation in blood can reveal impacts across the lifespan. Methods In the EXPANSE project, we conducted an inverse variance-weighted meta-analysis of epigenome-wide association studies of seven European cohorts. Urban exposures were estimated at participants' home addresses and included air pollution (PM2.5, NO 2 , O 3 ), light at night, modified soil-adjusted vegetation index, and urbanicity. Findings DNA methylation was measured in blood samples from 1778 children (4–10 years), 878 adolescents (16 years), and 5975 adults (18–87 years). PM2.5, NO 2 , and greenness were associated with methylation differences in children, while greenness and urbanicity showed associations in adults. Regional analyses showed differentially methylated regions (DMRs) across all life stages. Pathway analysis showed that monthly NO 2 in children was linked to immune and infectious disease pathways, whereas adult urbanicity was associated with immune pathways as well as PD-L1 expression and the PD-1 checkpoint pathway in cancer. Interpretation Urban environmental factors induce DNA methylation changes across life stages, with stronger associations in young children and adults. We observed a distinct contrast in the methylation changes...