Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

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  • dc.contributor.author Küpers, Leanne K.
  • dc.contributor.author Salas Díaz, Lucas Andrés, 1980-
  • dc.contributor.author Bustamante Pineda, Mariona
  • dc.contributor.author Kogevinas, Manolis
  • dc.contributor.author Vrijheid, Martine
  • dc.contributor.author Sunyer Deu, Jordi
  • dc.contributor.author Felix, Janine Frédérique
  • dc.date.accessioned 2019-06-04T07:31:45Z
  • dc.date.available 2019-06-04T07:31:45Z
  • dc.date.issued 2019
  • dc.description.abstract Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Küpers LK, Monnereau C, Sharp GC, Yousefi P, Salas LA, Ghantous A et al. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight. Nat Commun. 2019;10(1):1893. DOI: 10.1038/s41467-019-09671-3
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-09671-3
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/41696
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nature Communications. 2019;10(1):1893
  • dc.rights © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword DNA methylation
  • dc.subject.keyword Epidemiology
  • dc.subject.keyword Epigenetics
  • dc.subject.keyword Paediatric research
  • dc.title Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion