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

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. Me...

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Autores: Merid, Simon Kebede, Kogevinas, Manolis, Bustamante Pineda, Mariona, Vrijheid, Martine, Sunyer Deu, Jordi, Antó i Boqué, Josep Maria, Melén, Erik
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/44911
Acceso en línea:http://hdl.handle.net/10230/44911
http://dx.doi.org/10.1186/s13073-020-0716-9
Access Level:acceso abierto
Palabra clave:Development
Epigenetics
Gestational age
Preterm birth
Transcriptomics
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spelling Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational ageMerid, Simon KebedeKogevinas, ManolisBustamante Pineda, MarionaVrijheid, MartineSunyer Deu, JordiAntó i Boqué, Josep MariaMelén, ErikDevelopmentEpigeneticsGestational agePreterm birthTranscriptomicsBackground: 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.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.BioMed Central202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44911http://dx.doi.org/10.1186/s13073-020-0716-9reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésGenome Medicine. 2020 Mar 2;12(1):25info:eu-repo/grantAgreement/EC/H2020/757919Copyright © 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.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/449112026-06-12T07:21:37Z
dc.title.none.fl_str_mv Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
title Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
spellingShingle Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
Merid, Simon Kebede
Development
Epigenetics
Gestational age
Preterm birth
Transcriptomics
title_short Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
title_full Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
title_fullStr Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
title_full_unstemmed Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
title_sort Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
dc.creator.none.fl_str_mv Merid, Simon Kebede
Kogevinas, Manolis
Bustamante Pineda, Mariona
Vrijheid, Martine
Sunyer Deu, Jordi
Antó i Boqué, Josep Maria
Melén, Erik
author Merid, Simon Kebede
author_facet Merid, Simon Kebede
Kogevinas, Manolis
Bustamante Pineda, Mariona
Vrijheid, Martine
Sunyer Deu, Jordi
Antó i Boqué, Josep Maria
Melén, Erik
author_role author
author2 Kogevinas, Manolis
Bustamante Pineda, Mariona
Vrijheid, Martine
Sunyer Deu, Jordi
Antó i Boqué, Josep Maria
Melén, Erik
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Development
Epigenetics
Gestational age
Preterm birth
Transcriptomics
topic Development
Epigenetics
Gestational age
Preterm birth
Transcriptomics
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/44911
http://dx.doi.org/10.1186/s13073-020-0716-9
url http://hdl.handle.net/10230/44911
http://dx.doi.org/10.1186/s13073-020-0716-9
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Genome Medicine. 2020 Mar 2;12(1):25
info:eu-repo/grantAgreement/EC/H2020/757919
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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