The emerging landscape of dynamic DNA methylation in early childhood.
BMC Genomics
; 18(1): 25, 2017 01 05.
Article
em En
| MEDLINE
| ID: mdl-28056824
ABSTRACT
BACKGROUND:
DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood.RESULTS:
By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of p < 1.14 × 10-7. Genes with an increase in age-differential methylation were enriched in pathways related to 'development', and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease.CONCLUSION:
Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenvolvimento Infantil
/
Metilação de DNA
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Epigênese Genética
/
Epigenômica
Tipo de estudo:
Prognostic_studies
Limite:
Child
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Child, preschool
/
Female
/
Humans
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Infant
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Newborn
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Pregnancy
Idioma:
En
Revista:
BMC Genomics
Assunto da revista:
GENETICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Holanda