The emerging landscape of dynamic DNA methylation in early childhood

BMC Genomics

Research Article

Cilla Söderhäll¹  Juha Kere²  Inger Kull³  Cisca Wijmenga⁴  Marc Jan Bonder⁴  Pieter van der Vlies⁴  Yang Li⁴  Alexandra Zhernakova⁴  Cleo C. van Diemen⁴  Bianca van Rijkom⁴  Erik Melén⁵  Gerard H. Koppelman⁶  Dirkje S. Postma⁷  Cheng-Jian Xu⁸  Soesma A. Jankipersadsing⁸  Nour Baïz⁹  Isabella Annesi-Maesano⁹  Jocelyne Just^1,10  Mariona Bustamante^1,11  Josep Maria Antó^1,12  Jordi Sunyer^1,12  Ulrike Gehring^1,13  Jean Bousquet^1,14 

[1] Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden;Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden;Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden;Folkhälsan Institute of Genetics and Research Programs Unit, University of Helsinki, Helsinki, Finland;Department of Clinical Science and Education, Stockholm South General Hospital, Karolinska Institutet, and Sachs’ Children’s Hospital, SE-118 83, Stockholm, Sweden;Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;Department of Paediatric Pulmonology and Paediatric Allergy, Beatrix Children’s Hospital, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;Department of Paediatric Pulmonology and Paediatric Allergy, University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, GRIAC Research Institute, Groningen, The Netherlands;Department of Pulmonology, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;Department of Pulmonology, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;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;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;Department of Allergology-Centre de l’Asthme et des Allergies, Hôpital d’Enfants Armand Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France;ISGlobal, Centre for Research in Environmental Epidemiology, Barcelona, Spain;Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain;Universitat Pompeu Fabra (UPF), Barcelona, Spain;CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain;ISGlobal, Centre for Research in Environmental Epidemiology, Barcelona, Spain;Universitat Pompeu Fabra (UPF), Barcelona, Spain;CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain;IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain;Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands;University Hospital, Montpellier, France;MACVIA-France, Contre les Maladies Chroniques pour un VIeillissement Actif en France, European Innovation Partnership on Active and Healthy Ageing Reference Site, Paris, France;INSERM, VIMA: Ageing and chronic diseases. Epidemiological and public health approaches, U1168, Paris, France;UVSQ, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, Versailles, France;

关键词: DNA methylation;    Aging;    Methylation quantitative trait loci;    Maternal smoking;   

DOI  :  10.1186/s12864-016-3452-1

 received in 2016-07-20, accepted in 2016-12-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundDNA 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.ResultsBy 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.ConclusionOur study provides new insights into the dynamic epigenetic landscape of the first 8 years of life.

【 授权许可】

CC BY   
© The Author(s). 2017