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Trans. R. Soc. B"],"published-print":{"date-parts":[[2019,4,15]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>in utero<\/jats:italic>\n                    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\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 1 \u00d7 10\n                    <jats:sup>\u22127<\/jats:sup>\n                    . Our EWAS of maternal smoking during pregnancy identified 110 DMPs in neonatal blood, replicating previously reported genomic loci, including\n                    <jats:italic>AHRR<\/jats:italic>\n                    . 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.\n                  <\/jats:p>\n                  <jats:p>This article is part of the theme issue \u2018Developing differences: early-life effects and evolutionary medicine\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2018.0120","type":"journal-article","created":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T03:05:36Z","timestamp":1551063936000},"page":"20180120","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":60,"title":["Variable DNA methylation in neonates mediates the association between prenatal smoking and birth weight"],"prefix":"10.1098","volume":"374","author":[{"given":"Eilis","family":"Hannon","sequence":"first","affiliation":[{"name":"University of Exeter Medical School, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Schendel","sequence":"additional","affiliation":[{"name":"Department of Public Health, Aarhus University, Aarhus, Denmark"},{"name":"National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark"},{"name":"The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Ladd-Acosta","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA"},{"name":"Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2284-5744","authenticated-orcid":true,"given":"Jakob","family":"Grove","sequence":"additional","affiliation":[{"name":"Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark"},{"name":"Department of Biomedicine \u2013 Human Genetics, Aarhus University, Aarhus, Denmark"},{"name":"Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark"},{"name":"The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark"},{"name":"Centre for Genomics and Personalized Medicine, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine S\u00f8holm","family":"Hansen","sequence":"additional","affiliation":[{"name":"The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark"},{"name":"Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark"},{"name":"Institute of Biological Psychiatry, MHC Sct. 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