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BMC Genomics. 2017 Jan 5;18(1):25. doi: 10.1186/s12864-016-3452-1.

The emerging landscape of dynamic DNA methylation in early childhood.

Author information

1
Department of Pulmonology, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. c.xu@umcg.nl.
2
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. c.xu@umcg.nl.
3
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
4
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
5
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
6
ISGlobal, Centre for Research in Environmental Epidemiology, Barcelona, Spain.
7
Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.
8
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
9
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
10
Epidemiology of Allergic and Respiratory Diseases Department (EPAR), Sorbonne Université, UPMC Univ Paris 06, INSERM, Pierre Louis Institute of Epidemiology and Public Health, Saint-Antoine Medical School, Paris, France.
11
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
12
Department of Pulmonology, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
13
Department of Allergology-Centre de l'Asthme et des Allergies, Hôpital d'Enfants Armand Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France.
14
Department of Clinical Science and Education, Stockholm South General Hospital, Karolinska Institutet, and Sachs' Children's Hospital, SE-118 83, Stockholm, Sweden.
15
Folkhälsan Institute of Genetics and Research Programs Unit, University of Helsinki, Helsinki, Finland.
16
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
17
University Hospital, Montpellier, France.
18
MACVIA-France, Contre les Maladies Chroniques pour un VIeillissement Actif en France, European Innovation Partnership on Active and Healthy Ageing Reference Site, Paris, France.
19
INSERM, VIMA: Ageing and chronic diseases. Epidemiological and public health approaches, U1168, Paris, France.
20
UVSQ, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, Versailles, France.
21
Department of Paediatric Pulmonology and Paediatric Allergy, Beatrix Children's Hospital, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
22
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. y.li01@umcg.nl.
23
Department of Paediatric Pulmonology and Paediatric Allergy, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, GRIAC Research Institute, Groningen, The Netherlands.

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.

KEYWORDS:

Aging; DNA methylation; Maternal smoking; Methylation quantitative trait loci

PMID:
28056824
PMCID:
PMC5217260
DOI:
10.1186/s12864-016-3452-1
[Indexed for MEDLINE]
Free PMC Article

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