TY - JOUR
T1 - Green space exposure and blood DNA methylation at birth and in childhood – A multi-cohort study
AU - Aguilar-Lacasaña, Sofia
AU - Fontes Marques, Irene
AU - de Castro, Montserrat
AU - Dadvand, Payam
AU - Escribà, Xavier
AU - Fossati, Serena
AU - González, Juan R.
AU - Nieuwenhuijsen, Mark
AU - Alfano, Rossella
AU - Annesi-Maesano, Isabella
AU - Brescianini, Sonia
AU - Burrows, Kimberley
AU - Calas, Lucinda
AU - Elhakeem, Ahmed
AU - Heude, Barbara
AU - Hough, Amy
AU - Isaevska, Elena
AU - W V Jaddoe, Vincent
AU - Lawlor, Deborah A.
AU - Monaghan, Genevieve
AU - Nawrot, Tim
AU - Plusquin, Michelle
AU - Richiardi, Lorenzo
AU - Watmuff, Aidan
AU - Yang, Tiffany C.
AU - Vrijheid, Martine
AU - F Felix, Janine
AU - Bustamante, Mariona
N1 - Publisher Copyright: © 2024 The Author(s)
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85193590789
U2 - 10.1016/j.envint.2024.108684
DO - 10.1016/j.envint.2024.108684
M3 - Article
C2 - 38776651
AN - SCOPUS:85193590789
SN - 0160-4120
VL - 188
JO - Environment international
JF - Environment international
M1 - 108684
ER -