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

Philos Trans R Soc Lond B Biol Sci 2019 Apr;374(1770):20180120

1 University of Exeter Medical School, University of Exeter , Exeter , UK.

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. 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'.

Download full-text PDF

Source
http://dx.doi.org/10.1098/rstb.2018.0120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460077PMC
April 2019
2 Reads

Publication Analysis

Top Keywords

birth weight
16
dna methylation
16
maternal smoking
16
gestational age
8
methylomic variation
8
birth
6
smoking
5
maternal
5
variation 1263
4
link maternal
4
1263 infants
4
exposure outcome
4
associated prenatal
4
reported genomic
4
neonatal methylomic
4
infants dna
4
confirming link
4
unique collection
4
obstetric factors
4
replicating reported
4

References

(Supplied by CrossRef)

Similar Publications