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Environ Health Perspect. 2018 Sep;126(9):97006. doi: 10.1289/EHP2034.

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

Author information

1
1 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts, USA.
2
2 The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam , Rotterdam, Netherlands.
3
3 Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, University Medical Center Rotterdam , Rotterdam, Netherlands.
4
4 Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam , Rotterdam, Netherlands.
5
5 Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston, Massachusetts, USA.
6
6 Department of Environmental Health, Harvard T. H. Chan School of Public Health , Boston, Massachusetts, USA.
7
7 Department of Environmental Health Sciences, Columbia University Mailman School of Public Health , New York, USA.
8
8 Department of Epidemiology, University of California, Berkeley School of Public Health , Berkeley, California, USA.
9
9 Department of Biostatistics, Harvard T.H Chan School of Public Health , Boston, Massachusetts, USA.
10
10 Diabetes Unit, Massachusetts General Hospital , Boston, Massachusetts, USA.
11
11 Environmental Influences on Child Health Outcomes (ECHO) Program, Office of the Director , National Institutes of Health , Bethesda, Maryland, USA.
12
12 The Netherlands Organization for Applied Scientific Research (TNO) , Delft, Netherlands.
13
13 Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam , Rotterdam, Netherlands.
14
14 Department of Pediatrics, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam , Rotterdam, Netherlands.

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.

PMID:
30226399
PMCID:
PMC6375460
DOI:
10.1289/EHP2034
[Indexed for MEDLINE]
Free PMC Article

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