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

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@article{9684a9d2402745788a957b667517fb98,
title = "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'.",
author = "Eilis Hannon and Diana Schendel and Christine Ladd-Acosta and Jakob Grove and Hansen, {Christine S{\o}holm} and Hougaard, {David Michael} and Michaeline Bresnahan and Ole Mors and Hollegaard, {Mads Vilhelm} and Marie B{\ae}kvad-Hansen and Mady Hornig and Mortensen, {Preben Bo} and B{\o}rglum, {Anders D} and Thomas Werge and Pedersen, {Marianne Gi{\o}rtz} and Merete Nordentoft and Buxbaum, {Joseph D} and {Daniele Fallin}, M and Jonas Bybjerg-Grauholm and Abraham Reichenberg and Jonathan Mill and {iPSYCH-Broad ASD Group}",
year = "2019",
month = "4",
day = "15",
doi = "10.1098/rstb.2018.0120",
language = "English",
volume = "374",
pages = "20180120",
journal = "Royal Society of London. Philosophical Transactions B. Biological Sciences",
issn = "0962-8436",
publisher = "The/Royal Society",
number = "1770",

}

RIS

TY - JOUR

T1 - Variable DNA methylation in neonates mediates the association between prenatal smoking and birth weight

AU - Hannon, Eilis

AU - Schendel, Diana

AU - Ladd-Acosta, Christine

AU - Grove, Jakob

AU - Hansen, Christine Søholm

AU - Hougaard, David Michael

AU - Bresnahan, Michaeline

AU - Mors, Ole

AU - Hollegaard, Mads Vilhelm

AU - Bækvad-Hansen, Marie

AU - Hornig, Mady

AU - Mortensen, Preben Bo

AU - Børglum, Anders D

AU - Werge, Thomas

AU - Pedersen, Marianne Giørtz

AU - Nordentoft, Merete

AU - Buxbaum, Joseph D

AU - Daniele Fallin, M

AU - Bybjerg-Grauholm, Jonas

AU - Reichenberg, Abraham

AU - Mill, Jonathan

AU - iPSYCH-Broad ASD Group

PY - 2019/4/15

Y1 - 2019/4/15

N2 - 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'.

AB - 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'.

U2 - 10.1098/rstb.2018.0120

DO - 10.1098/rstb.2018.0120

M3 - Journal article

VL - 374

SP - 20180120

JO - Royal Society of London. Philosophical Transactions B. Biological Sciences

JF - Royal Society of London. Philosophical Transactions B. Biological Sciences

SN - 0962-8436

IS - 1770

ER -

ID: 58594661