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

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dc.contributor.authorMerid, Simon Kebede
dc.contributor.authorNovoloaca, Alexei
dc.contributor.authorSharp, Gemma C.
dc.contributor.authorKüpers, Leanne K.
dc.contributor.authorKho, Alvin T.
dc.contributor.authorRoy, Ritu
dc.contributor.authorGao, Lu
dc.contributor.authorAnnesi-Maesano, Isabella
dc.contributor.authorJain, Pooja
dc.contributor.authorPlusquin, Michelle
dc.contributor.authorKogevinas, Manolis
dc.contributor.authorAllard, Catherine
dc.contributor.authorVehmeijer, Florianne O. L.
dc.contributor.authorKazmi, Nabila
dc.contributor.authorSalas, Lucas A.
dc.contributor.authorRezwan, Faisal I.
dc.contributor.authorZhang, Hongmei
dc.contributor.authorSebert, Sylvain
dc.contributor.authorCzamara, Darina
dc.contributor.authorRifas-Shiman, Sheryl L.
dc.contributor.authorMelton, Phillip E.
dc.contributor.authorLawlor, Debbie A.
dc.contributor.authorPershagen, Göran
dc.contributor.authorBreton, Carrie V.
dc.contributor.authorHuen, Karen
dc.date.accessioned2020-04-08T12:02:30Z
dc.date.available2020-04-08T12:02:30Z
dc.date.issued2020-03-02
dc.description.abstractBackground 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.en_UK
dc.identifier.citationSK Merid, A Novoloaca, GC Sharp, et al., (2020) Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age, Genome Medicine, Volume 12, 2020, Article 25en_UK
dc.identifier.issn1756-994X
dc.identifier.urihttps://doi.org/10.1186/s13073-020-0716-9
dc.identifier.urihttp://dspace.lib.cranfield.ac.uk/handle/1826/15385
dc.language.isoenen_UK
dc.publisherBioMed Centralen_UK
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectDevelopmenten_UK
dc.subjectEpigeneticsen_UK
dc.subjectGestational ageen_UK
dc.subjectPreterm birthen_UK
dc.subjectTranscriptomicsen_UK
dc.titleEpigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational ageen_UK
dc.typeArticleen_UK

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