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

Sofia Aguilar-Lacasaña; Irene Fontes Marques; Montserrat de Castro; Payam  Dadvand; Xavier Escribà; Serena Fossati; Juan González; Mark Nieuwenhuijsen; Rossella Alfonso; Isabella Annesi-Maesano; Sonia Brescianinii; Kimberley Burrows; Lucinda Calas; Ahmed  Elhakeem; Barbara Heude; Amy Hough; Elena Isaevska; Vincent W V Jaddoe; Debbie A Lawlor; Genevieve Monaghan; Tim S Nawrot; Michelle Plusquin; Lorenzo Richiardi; Aidan Watmuffl; Tiffany Yang; Martine Vrijheid; Janine F Felix; Mariona Bustamante

doi:10.1016/j.envint.2024.108684

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

Sofia Aguilar-Lacasaña^*, Irene Fontes Marques, Montserrat de Castro, Payam Dadvand, Xavier Escribà, Serena Fossati, Juan González, Mark Nieuwenhuijsen, Rossella Alfonso, Isabella Annesi-Maesano, Sonia Brescianinii, Kimberley Burrows, Lucinda Calas, Ahmed Elhakeem, Barbara Heude, Amy Hough, Elena Isaevska, Vincent W V Jaddoe, Debbie A Lawlor, Genevieve MonaghanTim S Nawrot, Michelle Plusquin, Lorenzo Richiardi, Aidan Watmuffl, Tiffany Yang, Martine Vrijheid, Janine F Felix, Mariona Bustamante

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

10 Citations (Scopus)

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 100m and 300m) and (ii) proximity to green space (having a green space ≥ 5,000 m2 within a distance of 300m). 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.

Original language	English
Article number	108684
Number of pages	38
Journal	Environment International
Volume	188
Early online date	23 Apr 2024
DOIs	https://doi.org/10.1016/j.envint.2024.108684
Publication status	E-pub ahead of print - 23 Apr 2024

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© 2024 The Author(s)

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Aguilar-Lacasaña, S., Marques, I. F., de Castro, M., Dadvand, P., Escribà, X., Fossati, S., González, J., Nieuwenhuijsen, M., Alfonso, R., Annesi-Maesano, I., Brescianinii, S., Burrows, K., Calas, L., Elhakeem, A., Heude, B., Hough, A., Isaevska, E., Jaddoe, V. W. V., Lawlor, D. A., ... Bustamante, M. (2024). Green space exposure and blood DNA methylation at birth and in childhood – A multi-cohort study. Environment International, 188, Article 108684. Advance online publication. https://doi.org/10.1016/j.envint.2024.108684

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title = "Green space exposure and blood DNA methylation at birth and in childhood – A multi-cohort study",

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 100m and 300m) and (ii) proximity to green space (having a green space ≥ 5,000 m2 within a distance of 300m). 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. ",

author = "Sofia Aguilar-Lacasa{\~n}a and Marques, \{Irene Fontes\} and \{de Castro\}, Montserrat and Payam Dadvand and Xavier Escrib{\`a} and Serena Fossati and Juan Gonz{\'a}lez and Mark Nieuwenhuijsen and Rossella Alfonso and Isabella Annesi-Maesano and Sonia Brescianinii and Kimberley Burrows and Lucinda Calas and Ahmed Elhakeem and Barbara Heude and Amy Hough and Elena Isaevska and Jaddoe, \{Vincent W V\} and Lawlor, \{Debbie A\} and Genevieve Monaghan and Nawrot, \{Tim S\} and Michelle Plusquin and Lorenzo Richiardi and Aidan Watmuffl and Tiffany Yang and Martine Vrijheid and Felix, \{Janine F\} and Mariona Bustamante",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = apr,

day = "23",

doi = "10.1016/j.envint.2024.108684",

language = "English",

volume = "188",

journal = "Environment International",

issn = "0160-4120",

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Aguilar-Lacasaña, S, Marques, IF, de Castro, M, Dadvand, P, Escribà, X, Fossati, S, González, J, Nieuwenhuijsen, M, Alfonso, R, Annesi-Maesano, I, Brescianinii, S, Burrows, K, Calas, L, Elhakeem, A, Heude, B, Hough, A, Isaevska, E, Jaddoe, VWV, Lawlor, DA , Monaghan, G, Nawrot, TS, Plusquin, M, Richiardi, L, Watmuffl, A, Yang, T, Vrijheid, M, Felix, JF & Bustamante, M 2024, 'Green space exposure and blood DNA methylation at birth and in childhood – A multi-cohort study', Environment International, vol. 188, 108684. https://doi.org/10.1016/j.envint.2024.108684

TY - JOUR

T1 - Green space exposure and blood DNA methylation at birth and in childhood – A multi-cohort study

AU - Aguilar-Lacasaña, Sofia

AU - Marques, Irene Fontes

AU - de Castro, Montserrat

AU - Dadvand, Payam

AU - Escribà, Xavier

AU - Fossati, Serena

AU - González, Juan

AU - Nieuwenhuijsen, Mark

AU - Alfonso, Rossella

AU - Annesi-Maesano, Isabella

AU - Brescianinii, Sonia

AU - Burrows, Kimberley

AU - Calas, Lucinda

AU - Elhakeem, Ahmed

AU - Heude, Barbara

AU - Hough, Amy

AU - Isaevska, Elena

AU - Jaddoe, Vincent W V

AU - Lawlor, Debbie A

AU - Monaghan, Genevieve

AU - Nawrot, Tim S

AU - Plusquin, Michelle

AU - Richiardi, Lorenzo

AU - Watmuffl, Aidan

AU - Yang, Tiffany

AU - Vrijheid, Martine

AU - Felix, Janine F

AU - Bustamante, Mariona

PY - 2024/4/23

Y1 - 2024/4/23

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 100m and 300m) and (ii) proximity to green space (having a green space ≥ 5,000 m2 within a distance of 300m). 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 100m and 300m) and (ii) proximity to green space (having a green space ≥ 5,000 m2 within a distance of 300m). 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.

U2 - 10.1016/j.envint.2024.108684

DO - 10.1016/j.envint.2024.108684

M3 - Article (Academic Journal)

C2 - 38776651

SN - 0160-4120

VL - 188

JO - Environment International

JF - Environment International

M1 - 108684

ER -

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

Abstract

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