Variable DNA methylation in neonates mediates the association between prenatal smoking and birth weight
Hannon, E; Schendel, D; Ladd-Acosta, C; et al.Grove, J; Hansen, CS; Hougaard, DM; Bresnahan, M; Mors, O; Hollegaard, MV; Bækvad-Hansen, M; Hornig, M; Mortensen, PB; Børglum, AD; Werge, T; Pedersen, MG; Nordentof, M; iPSYCH-Broad; Buxbaum, JD; Fallin, MD; Bybjerg-Grauholm, J; Reichenberg, A; Mill, J
Date: 25 February 2019
Journal
Philosophical Transactions B: Biological Sciences
Publisher
Royal Society
Publisher DOI
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. ...
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 prenatal exposures
including birth weight, gestational age and maternal smoking. We quantified neonatal methylomic variation in 1,263 infants using DNA isolated from a unique collection of archived
blood spots taken shortly after birth (mean = 6.08 days; sd = 3.24 days). An epigenome-wide
association study (EWAS) of gestational age and birth weight identified 4,299 and 18
differentially methylated positions (DMPs) respectively, at an experiment-wide significance
threshold of P < 1x10-7 13 . 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.
Institute of Biomedical & Clinical Science
Collections of Former Colleges
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