Socioeconomic status and DNA methylation from birth through mid-childhood: a prospective study in Project Viva.
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ABSTRACT:
SUBMITTER: Laubach ZM
PROVIDER: S-EPMC6802709 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
Publications
Socioeconomic status and DNA methylation from birth through mid-childhood: a prospective study in Project Viva.
Laubach Zachary M ZM Perng Wei W Cardenas Andres A Rifas-Shiman Sheryl L SL Oken Emily E DeMeo Dawn D Litonjua Augusto A AA Duca Radu-Corneliu RC Godderis Lode L Baccarelli Andrea A Hivert Marie-France MF
Epigenomics 20190911 12
<b>Aim:</b> We investigated associations of prenatal socioeconomic status (SES) with DNA methylation at birth, and to explore persistence of associations into early (∼3 years) and mid-childhood (∼7 years) among 609 mother-child pairs in a Boston-area prebirth cohort. <b>Materials & methods:</b> First, we created a prenatal SES index comprising individual- and neighborhood-level metrics and examined associations of low (lowest 10%) versus high (upper 90%) SES with genome-wide DNA methylation in c ...[more]
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Project description:BackgroundEpigenetic variability is hypothesized as a regulatory pathway through which prenatal exposures may influence child development and health.ObjectiveWe 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.MethodsWe 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.ResultsLiving 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.ConclusionsOur 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.
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Project description:BACKGROUND:Corticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood. METHODS:We investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n?=?239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn. RESULTS:Maternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P?<?0.05, ??=?0.64, SE?=?0.30). CONCLUSION:In our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood.
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