Autor/a:
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Xu, Cheng-Jian; Bonder, Marc Jan; Soderhall, Cilla; Bustamante Pineda, Mariona; Baiz, Nour; Gehring, Ulrike; Jankipersadsing, Soesma A.; Vlies, Pieter van der; Diemen, Cleo C. van; Rijkom, Bianca van; Just, Jocelyne; Kull, Inger; Kere, Juha; Antó i Boqué, Josep Maria; Bousquet, Jean; Zhernakova, Alexandra; Wijmenga, Cisca; Annesi-Maesano, Isabella; Sunyer Deu, Jordi; Melén, Erik; Li, Yang; Postma, Dirkje S.; Koppelman, Gerard H.
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Abstract:
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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 x 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. |