Welcome to the UPF Digital Repository

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Show simple item record

dc.contributor.author Merid, Simon Kebede
dc.contributor.author Kogevinas, Manolis
dc.contributor.author Bustamante Pineda, Mariona
dc.contributor.author Vrijheid, Martine
dc.contributor.author Sunyer Deu, Jordi
dc.contributor.author Antó i Boqué, Josep Maria
dc.contributor.author Melén, Erik
dc.date.accessioned 2020-06-05T06:28:27Z
dc.date.available 2020-06-05T06:28:27Z
dc.date.issued 2020
dc.identifier.citation Merid SK, Novoloaca A, Sharp GC, Küpers LK, Kho AT, Roy R, et al. Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age. Genome Med. 2020 Mar 2; 12(1):25. DOI: 10.1186/s13073-020-0716-9
dc.identifier.issn 1756-994X
dc.identifier.uri http://hdl.handle.net/10230/44911
dc.description.abstract Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
dc.description.sponsorship This study was specifically funded by a grant from the European Research Council (TRIBAL, grant agreement 757919). For all studies, detailed information can be found in Additional file 2: Supplementary information. Open access funding provided by Uppsala University.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartof Genome Medicine. 2020 Mar 2;12(1):25
dc.rights Copyright © The Author(s). 2020. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s13073-020-0716-9
dc.subject.keyword Development
dc.subject.keyword Epigenetics
dc.subject.keyword Gestational age
dc.subject.keyword Preterm birth
dc.subject.keyword Transcriptomics
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/757919
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account

Statistics

In collaboration with Compliant to Partaking