Variable DNA methylation in neonates mediates the association between prenatal smoking and birth weight

Abstract

There is great interest in the role epigenetic variation induced by non-genetic exposures may play in the context of health and disease. In particular, DNA methylation has previously been shown to be highly dynamic during the earliest stages of development and is influenced by in utero exposures such as maternal smoking and medication. In this study we sought to identify the specific DNA methylation differences in blood associated with prenatal and birth factors, including birth weight, gestational age and maternal smoking. We quantified neonatal methylomic variation in 1263 infants using DNA isolated from a unique collection of archived blood spots taken shortly after birth (mean = 6.08 days; s.d. = 3.24 days). An epigenome-wide association study (EWAS) of gestational age and birth weight identified 4299 and 18 differentially methylated positions (DMPs) respectively, at an experiment-wide significance threshold of p < 1 × 10 −7 . Our EWAS of maternal smoking during pregnancy identified 110 DMPs in neonatal blood, replicating previously reported genomic loci, including AHRR . Finally, we tested the hypothesis that DNA methylation mediates the relationship between maternal smoking and lower birth weight, finding evidence that methylomic variation at three DMPs may link exposure to outcome. These findings complement an expanding literature on the epigenomic consequences of prenatal exposures and obstetric factors, confirming a link between the maternal environment and gene regulation in neonates. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

“…The results were consistent when restricted to births at term, demonstrating that the majority of our results were not driven by preterm births. We confirmed many of the findings from previously published EWAS of gestational age [23,26,27,29,30,67] and found a very high correlation between the significant CpG point estimates in previously published datasets compared to our study (e.g. corr = 0.92 between Hannon et al CpGs and our data; Additional file 1: Table S16), but importantly, we also found 3343 CpGs corresponding to 2577 genes that had not been described previously.…”

Large-scale analysis of DNA methylation identifies cellular alterations in blood from psychosis patients and molecular biomarkers of treatment-resistant schizophrenia

“…medications, stress, etc). The mean difference in DNA methylation between cases and controls for both psychosis and schizophrenia was small, consistent with other blood-based EWAS of schizophrenia 66 and complex traits [75][76][77] in general. While individually they may be too small to have a strong predictive power as a biomarker, together they may have utility as a molecular classifier 78 .…”

Smoking and Smoking Cessation in the Risk for Fetal Growth Restriction and Low Birth Weight and Additive Effect of Maternal Obesity

“…Relationships between smoking in the first trimester and lower maternal serum selenium levels at the end of the first trimester [12,27], as well as between maternal obesity/overweight and lower maternal selenium levels, were also found [12,27]. There is evidence of oxidative damage to lipids and proteins in smokers, and an increase in oxidative damage to DNA has been found in various biological materials [35]. DNA methylation that mediates between smoking and lower birth weight can also be a factor linking this unfavorable fetal outcome with adverse long-term health outcomes [35,36].…”

“…There is evidence of oxidative damage to lipids and proteins in smokers, and an increase in oxidative damage to DNA has been found in various biological materials [35]. DNA methylation that mediates between smoking and lower birth weight can also be a factor linking this unfavorable fetal outcome with adverse long-term health outcomes [35,36]. It should also be taken into account that smoking women may lead a different lifestyle that includes, for example, an unhealthy diet and other "unhealthy" behaviors [37].…”