Journal
BMC GENOMICS
Volume 18, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12864-016-3452-1
Keywords
DNA methylation; Aging; Methylation quantitative trait loci; Maternal smoking
Funding
- MeDALL
- European Union under the Health Cooperation Work Program of the 7th Framework program [261357]
- Swedish Foundation for Strategic Research (SSF) [RBc08-0027]
- Swedish Research Council
- Swedish Heart-Lung Foundation
- Stockholm County Council (ALF)
- SFO Epidemiology program at the Karolinska Institutet
- Instituto de Salud Carlos III [Red INMA G03/176, CB06/02/0041, PI041436, PI081151]
- Generalitat de Catalunya-CIRIT [1999SGR 00241]
- Fundacio La Marato de TV3 [090430]
- French Ministry of Research: IFR program
- INSERM Nutrition Research Program
- French Ministry of Health: Perinatality Program
- French National Institute for Population Health Surveillance (INVS)
- Paris-Sud University
- French National Institute for Health Education (INPES)
- Nestle
- Mutuelle Generale de l'Education Nationale (MGEN)
- French speaking association
- Sao Paulo Research Foundation (FAPESP) [2012/51290-6]
- EU
- Netherlands Organization for Health Research and Development (ZonMw)
- Netherlands Organization for Scientific Research (NWO)
- Netherlands Asthma Fund
- Netherlands Ministry of Spatial Planning, Housing, and the Environment
- Netherlands Ministry of Health, Welfare, and Sport
- NWO (VENI) [863.13.011]
- FEDER funds [PS09/00432]
- Swedish Foundation for Strategic Research (SSF) [RBc08-0027] Funding Source: Swedish Foundation for Strategic Research (SSF)
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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 rho < 1.14x10(-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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