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Title: The emerging landscape of dynamic DNA methylation in early childhood
Author: 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.
Keywords: Metilació
Issue Date: 5-Jan-2017
Publisher: BioMed Central
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 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.
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It is part of: BMC Genomics, 2017, vol. 18, num. 25
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ISSN: 1471-2164
Appears in Collections:Articles publicats en revistes (ISGlobal)

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