학술논문
Residential Proximity to Major Roadways at Birth, DNA Methylation at Birth and Midchildhood, and Childhood Cognitive Test Scores: Project Viva (Massachusetts, USA).
Document Type
Article
Author
Cheng Peng; den Dekker, Martijn; Cardenas, Andres; Rifas-Shiman, Sheryl L.; Gibson, Heike; Agha, Golareh; Harris, Maria H.; Coull, Brent A.; Schwartz, Joel; Litonjua, Augusto A.; DeMeo, Dawn L.; Hivert, Marie-France; Gilman, Matthew W.; Sagiv, Sharon K.; de Kluizenaar, Yvonne; Felix, Janine F.; Jaddoe, Vincent W.; Oken, Emily; Duijts, Liesbeth; Gold, Diane R.
Source
Subject
*AUTOMOBILE emissions
*CONFIDENCE intervals
*CORD blood
*NEUROLOGIC manifestations of general diseases
*PSYCHOLOGICAL tests
*RESEARCH funding
*STATISTICS
*DATA analysis
*DATA analysis software
*DNA methylation
*DESCRIPTIVE statistics
*EPIGENOMICS
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Language
ISSN
0091-6765
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 residentialproximity- to-roadways at birth using robust linear regression [false discovery rate ðFDRÞ<0:05]. We also estimated association between proximityto- roadways at birth and methylation of the same sites in blood samples collected at age 7-11 y (N=415). We ran the same analyses in the Generation R Study for replication (N=641). 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. [ABSTRACT FROM AUTHOR]