2026-04-17T07:47:24Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/607132025-12-12T04:24:59Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Aguilar Lacasaña, Sofía author Castro, Montserrat de author Dadvand, Payam author Escribà Montagut, Xavier author Fossati, Serena author González, Juan Ramón author Nieuwenhuijsen, Mark J. author Vrijheid, Martine author Bustamante Pineda, Mariona author 2024-07-10T06:20:28Z 2024-07-10T06:20:28Z 2024 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. 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. Child blood Cord blood DMP DMR DNA methylation Green space Green space exposure and blood DNA methylation at birth and in childhood - A multi-cohort study