» Articles » PMID: 30226399

Residential Proximity to Major Roadways at Birth, DNA Methylation at Birth and Midchildhood, and Childhood Cognitive Test Scores: Project Viva(Massachusetts, USA)

Abstract

Background: Epigenetic variability is hypothesized as a regulatory pathway through which prenatal exposures may influence child development and health.

Objective: We sought to examine the associations of residential proximity to roadways at birth and epigenome-wide DNA methylation. We also assessed associations of differential methylation with child cognitive outcomes.

Methods: We estimated residential proximity to roadways at birth using a geographic information system (GIS) and cord blood methylation using Illumina's HumanMethylation450-array in 482 mother-child pairs in Project Viva. We identified individual CpGs associated with residential-proximity-to-roadways at birth using robust linear regression [[Formula: see text]]. We also estimated association between proximity-to-roadways at birth and methylation of the same sites in blood samples collected at age 7-11 y ([Formula: see text]). We ran the same analyses in the Generation R Study for replication ([Formula: see text]). In Project Viva, we investigated associations of differential methylation at birth with midchildhood cognition using linear regression.

Results: Living closer to major roadways at birth was associated with higher cord blood (and-more weakly-midchildhood blood) methylation of four sites in LAMB2. For each halving of residential-proximity-to-major-roadways, we observed a 0.82% increase in DNA methylation at cg05654765 [95% confidence interval (CI): (0.54%, 1.10%)], 0.88% at cg14099457 [95% CI: (0.56%, 1.19%)], 0.19% at cg03732535 [95% CI: (0.11%, 0.28)], and 1.08% at cg02954987 [95% CI: (0.65%, 1.51%)]. Higher cord blood methylation of these sites was associated with lower midchildhood nonverbal cognitive scores. Our results did not replicate in the Generation R Study.

Conclusions: Our discovery results must be interpreted with caution, given that they were not replicated in a separate cohort. However, living close to major roadways at birth was associated with cord blood methylation of sites in LAMB2-a gene known to be linked to axonal development-in our U.S. cohort. Higher methylation of these sites associated with lower nonverbal cognitive scores at age 7-11 y in the same children. https://doi.org/10.1289/EHP2034.

Citing Articles

A systematic review of associations between the environment, DNA methylation, and cognition.

Glover S, Illyuk J, Hill C, McGuinness B, McKnight A, Hunter R Environ Epigenet. 2025; 11(1):dvae027.

PMID: 39882510 PMC: 11776599. DOI: 10.1093/eep/dvae027.


Linking Prenatal Environmental Exposures to Lifetime Health with Epigenome-Wide Association Studies: State-of-the-Science Review and Future Recommendations.

Bakulski K, Blostein F, London S Environ Health Perspect. 2023; 131(12):126001.

PMID: 38048101 PMC: 10695268. DOI: 10.1289/EHP12956.


Disparities in Toxic Chemical Exposures and Associated Neurodevelopmental Outcomes: A Scoping Review and Systematic Evidence Map of the Epidemiological Literature.

Payne-Sturges D, Taiwo T, Ellickson K, Mullen H, Tchangalova N, Anderko L Environ Health Perspect. 2023; 131(9):96001.

PMID: 37754677 PMC: 10525348. DOI: 10.1289/EHP11750.


Ambient air pollution during pregnancy and DNA methylation in umbilical cord blood, with potential mediation of associations with infant adiposity: The Healthy Start study.

Starling A, Wood C, Liu C, Kechris K, Yang I, Friedman C Environ Res. 2022; 214(Pt 1):113881.

PMID: 35835166 PMC: 10402394. DOI: 10.1016/j.envres.2022.113881.


Maternal depression and adverse neighbourhood conditions during pregnancy are associated with gestational epigenetic age deceleration.

Appleton A, Lin B, Kennedy E, Holdsworth E Epigenetics. 2022; 17(13):1905-1919.

PMID: 35770941 PMC: 9665127. DOI: 10.1080/15592294.2022.2090657.


References
1.
Doherty A, MANN M, Tremblay K, Bartolomei M, Schultz R . Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol Reprod. 2000; 62(6):1526-35. DOI: 10.1095/biolreprod62.6.1526. View

2.
Young L, Fernandes K, McEvoy T, Butterwith S, Gutierrez C, Carolan C . Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet. 2001; 27(2):153-4. DOI: 10.1038/84769. View

3.
Khosla S, Dean W, Brown D, Reik W, Feil R . Culture of preimplantation mouse embryos affects fetal development and the expression of imprinted genes. Biol Reprod. 2001; 64(3):918-26. DOI: 10.1095/biolreprod64.3.918. View

4.
Lieth E, Cardasis C, Fallon J . Muscle-derived agrin in cultured myotubes: expression in the basal lamina and at induced acetylcholine receptor clusters. Dev Biol. 1992; 149(1):41-54. DOI: 10.1016/0012-1606(92)90262-f. View

5.
Johnson W, Li C, Rabinovic A . Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2006; 8(1):118-27. DOI: 10.1093/biostatistics/kxj037. View