The emerging landscape of dynamic DNA methylation in early childhood

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• dc.contributor.author Xu, Cheng-Jianca
• dc.contributor.author Bustamante Pineda, Marionaca
• dc.contributor.author Antó i Boqué, Josep Mariaca
• dc.contributor.author Sunyer Deu, Jordica
• dc.contributor.author Koppelman, Gerard H.ca
• dc.date.accessioned 2017-03-14T14:30:08Z
• dc.date.available 2017-03-14T14:30:08Z
• dc.date.issued 2017
• dc.description.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.
• dc.description.sponsorship We are grateful for financial support from MeDALL. MeDALL is a collaborative project supported by the European Union under the Health Cooperation Work Program of the 7th Framework program (grant agreement number 261357). BAMSE: BAMSE was supported by the Swedish Foundation for Strategic Research (SSF, RBc08-0027, EpiGene project), the Swedish Research Council, the Swedish Heart-Lung Foundation, Stockholm County Council (ALF), and the SFO Epidemiology program at the Karolinska Institutet. In addition, we would like to thank Eva Hallner, Sara Nilsson, and André Lauber at the BAMSE secretariat for invaluable support, as well as Mutation Analysis Facility (MAF) at Karolinska Institutet for genome-wide methylation analysis, and Ingrid Delin for excellent technical assistance. INMA: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds, PS09/00432), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La Marató de TV3 (090430)). DNA extraction and genotyping were performed at the Spanish National Genotyping Centre (CEGEN-Barcelona). We thank all the participants for their generous collaboration and Silvia Fochs, NuriaPey, and Muriel Ferrer for their assistance in contacting families and administering questionnaires.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Xu C-J, Jan Bonder M, Söderhäll C, Bustamante M, Baïz N, Gehring U et al. The emerging landscape of dynamic DNA methylation in early childhood. BMC Genomics. 2017;18:25. DOI: 10.1186/s12864-016-3452-1
• dc.identifier.doi http://dx.doi.org/10.1186/s12864-016-3452-1
• dc.identifier.issn 1471-2164
• dc.identifier.uri http://hdl.handle.net/10230/28229
• dc.language.iso eng
• dc.publisher BioMed Centralca
• dc.relation.ispartof BMC Genomics. 2017;18:25
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/261357
• dc.rights 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword DNA methylation
• dc.subject.keyword Aging
• dc.subject.keyword Methylation quatitative trait loci
• dc.subject.keyword Maternal smoking
• dc.title The emerging landscape of dynamic DNA methylation in early childhoodca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion