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Green space exposure and blood DNA methylation at birth and in childhood - A multi-cohort study

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dc.contributor.author Aguilar Lacasaña, Sofía
dc.contributor.author Castro, Montserrat de
dc.contributor.author Dadvand, Payam
dc.contributor.author Escribà Montagut, Xavier
dc.contributor.author Fossati, Serena
dc.contributor.author González, Juan Ramón
dc.contributor.author Nieuwenhuijsen, Mark J.
dc.contributor.author Vrijheid, Martine
dc.contributor.author Bustamante Pineda, Mariona
dc.date.accessioned 2024-07-10T06:20:28Z
dc.date.available 2024-07-10T06:20:28Z
dc.date.issued 2024
dc.identifier.citation Aguilar-Lacasaña S, Fontes Marques I, de Castro M, Dadvand P, Escribà X, Fossati S, et al. Green space exposure and blood DNA methylation at birth and in childhood - A multi-cohort study. Environ Int. 2024 Jun;188:108684. DOI: 10.1016/j.envint.2024.108684
dc.identifier.issn 0160-4120
dc.identifier.uri http://hdl.handle.net/10230/60713
dc.description.abstract Green space exposure has been associated with improved mental, physical and general health. However, the underlying biological mechanisms remain largely unknown. The aim of this study was to investigate the association between green space exposure and cord and child blood DNA methylation. Data from eight European birth cohorts with a total of 2,988 newborns and 1,849 children were used. Two indicators of residential green space exposure were assessed: (i) surrounding greenness (satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 100 m and 300 m) and (ii) proximity to green space (having a green space ≥ 5,000 m2 within a distance of 300 m). For these indicators we assessed two exposure windows: (i) pregnancy, and (ii) the period from pregnancy to child blood DNA methylation assessment, named as cumulative exposure. DNA methylation was measured with the Illumina 450K or EPIC arrays. To identify differentially methylated positions (DMPs) we fitted robust linear regression models between pregnancy green space exposure and cord blood DNA methylation and between cumulative green space exposure and child blood DNA methylation. Two sensitivity analyses were conducted: (i) without adjusting for cellular composition, and (ii) adjusting for air pollution. Cohort results were combined through fixed-effect inverse variance weighted meta-analyses. Differentially methylated regions (DMRs) were identified from meta-analysed results using the Enmix-combp and DMRcate methods. There was no statistical evidence of pregnancy or cumulative exposures associating with any DMP (False Discovery Rate, FDR, p-value < 0.05). However, surrounding greenness exposure was inversely associated with four DMRs (three in cord blood and one in child blood) annotated to ADAMTS2, KCNQ1DN, SLC6A12 and SDK1 genes. Results did not change substantially in the sensitivity analyses. Overall, we found little evidence of the association between green space exposure and blood DNA methylation. Although we identified associations between surrounding greenness exposure with four DMRs, these findings require replication.
dc.description.sponsorship This work was supported by the European Union’s Horizon 2020 research and innovation program − ATHLETE project [grant number 874583], LIFECYCLE project [grant number 733206], LongITools project [grant number 874739] and HELIX project [grant number 308333]. Sofía Aguilar-Lacasaña was funded by the FI-AGAUR Predoctoral contract [2023 FI-2 00797]. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program [CEX2018-000806-S] and Fondo Europeo de Desarrollo Regional, UE [PID2021-122855OB-I00], and support from the Generalitat de Catalunya through the CERCA Program and Ministery of Research and Universities [2021 SGR 01563]. Details of funding for each study and for contributions of individual studies can be found in Appendix B: Supplementary methods. No funders listed here or in Appendix B influenced the study aim, design, analysis or interpretation of results. The results expressed here are those of the authors and not necessarily any listed funder.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Environ Int. 2024 Jun;188:108684
dc.rights © 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.title Green space exposure and blood DNA methylation at birth and in childhood - A multi-cohort study
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.envint.2024.108684
dc.subject.keyword Child blood
dc.subject.keyword Cord blood
dc.subject.keyword DMP
dc.subject.keyword DMR
dc.subject.keyword DNA methylation
dc.subject.keyword Green space
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/733206
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874739
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000806-S
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-122855OB-I00
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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