dc.contributor.author | Hannon, E | |
dc.contributor.author | Schendel, D | |
dc.contributor.author | Ladd-Acosta, C | |
dc.contributor.author | Grove, J | |
dc.contributor.author | Hansen, CS | |
dc.contributor.author | Hougaard, DM | |
dc.contributor.author | Bresnahan, M | |
dc.contributor.author | Mors, O | |
dc.contributor.author | Hollegaard, MV | |
dc.contributor.author | Bækvad-Hansen, M | |
dc.contributor.author | Hornig, M | |
dc.contributor.author | Mortensen, PB | |
dc.contributor.author | Børglum, AD | |
dc.contributor.author | Werge, T | |
dc.contributor.author | Pedersen, MG | |
dc.contributor.author | Nordentof, M | |
dc.contributor.author | iPSYCH-Broad | |
dc.contributor.author | Buxbaum, JD | |
dc.contributor.author | Fallin, MD | |
dc.contributor.author | Bybjerg-Grauholm, J | |
dc.contributor.author | Reichenberg, A | |
dc.contributor.author | Mill, J | |
dc.date.accessioned | 2019-01-29T11:55:56Z | |
dc.date.issued | 2019-02-25 | |
dc.description.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 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. | en_GB |
dc.description.sponsorship | iPSYCH | en_GB |
dc.description.sponsorship | Lundbeck Foundation | en_GB |
dc.identifier.citation | Vol. 374 (1770). Published online 25 February 2019. | en_GB |
dc.identifier.doi | 10.1098/rstb.2018.0120 | |
dc.identifier.uri | http://hdl.handle.net/10871/35611 | |
dc.language.iso | en | en_GB |
dc.publisher | Royal Society | en_GB |
dc.rights | © 2019 The Author(s). Published by the Royal Society. All rights reserved. | |
dc.subject | DNA methylation | en_GB |
dc.subject | birth weight | en_GB |
dc.subject | gestational age | en_GB |
dc.subject | maternal smoking | en_GB |
dc.subject | epigenome wide association study (EWAS) | en_GB |
dc.subject | mediation analysis | en_GB |
dc.title | Variable DNA methylation in neonates mediates the association between prenatal smoking and birth weight | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-01-29T11:55:56Z | |
dc.identifier.issn | 0962-8436 | |
dc.description | This is the author accepted manuscript. The final version is available from The Royal Society via the DOI in this record. | en_GB |
dc.description | Data Accessibility:
Given the nature of the MINERvA cohort, access to data can only be provided through
secured systems which comply with the current Danish and EU data standards. To comply
with the study’s ethical approval, access to the raw data is only available to qualified
researchers upon request. All summary statistics and analysis scripts are available directly
from the authors (please contact Jonas Bybjerg-Grauholm at JOGR@ssi.dk). R scripts used
to perform the quality control of these data are available on GitHub
(https://github.com/ejh243/MinervaASDEWAS.git) and have been archived in Zenado at
https://zenodo.org/badge/latestdoi/116149862 and scripts for the analyses reported in this
manuscript are available on GitHub (https://github.com/ejh243/MinervaNeonatalEWAS.git)
and have been archived in Zenado at https://doi.org/10.5281/zenodo.1303340. | en_GB |
dc.identifier.journal | Philosophical Transactions B: Biological Sciences | en_GB |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2018-11-21 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2018-11-21 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-01-27T17:30:32Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2019-03-05T10:33:25Z | |
refterms.panel | A | en_GB |