Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Epigenome-wide change and variation in DNA methylation from birth to late adolescence

View ORCID ProfileRosa H. Mulder, View ORCID ProfileAlexander Neumann, View ORCID ProfileCharlotte A. M. Cecil, View ORCID ProfileEsther Walton, View ORCID ProfileLotte C. Houtepen, View ORCID ProfileAndrew J. Simpkin, View ORCID ProfileJolien Rijlaarsdam, View ORCID ProfileBastiaan T. Heijmans, View ORCID ProfileTom R. Gaunt, View ORCID ProfileJanine F. Felix, View ORCID ProfileVincent W. V. Jaddoe, Marian J. Bakermans-Kranenburg, View ORCID ProfileHenning Tiemeier, View ORCID ProfileCaroline L. Relton, View ORCID ProfileMarinus H. van IJzendoorn, View ORCID ProfileMatthew Suderman
doi: https://doi.org/10.1101/2020.06.09.142620
Rosa H. Mulder
1Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
2Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
3Institute of Education and Child Studies, Leiden University, Leiden, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rosa H. Mulder
Alexander Neumann
1Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
2Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
4Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Qc, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alexander Neumann
Charlotte A. M. Cecil
1Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
5Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
6Department of Psychology, Institute of Psychology, Psychiatry & Neuroscience, King’s College London, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Charlotte A. M. Cecil
Esther Walton
7MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
8Department of Psychology, University of Bath, Bath, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Esther Walton
Lotte C. Houtepen
7MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Lotte C. Houtepen
Andrew J. Simpkin
7MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
9School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, Ireland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Andrew J. Simpkin
Jolien Rijlaarsdam
1Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
2Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jolien Rijlaarsdam
Bastiaan T. Heijmans
10Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Bastiaan T. Heijmans
Tom R. Gaunt
7MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tom R. Gaunt
Janine F. Felix
2Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
11Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Janine F. Felix
Vincent W. V. Jaddoe
2Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
11Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Vincent W. V. Jaddoe
Marian J. Bakermans-Kranenburg
12Clinical Child & Family Studies, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Henning Tiemeier
1Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
13Department of Social and Behavioral Science, Harvard TH Chan School of Public Health, Boston USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Henning Tiemeier
Caroline L. Relton
7MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Caroline L. Relton
Marinus H. van IJzendoorn
14Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, the Netherlands
15School of Clinical Medicine, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marinus H. van IJzendoorn
Matthew Suderman
7MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Matthew Suderman
  • For correspondence: matthew.suderman@bristol.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5,019 blood samples collected at multiple time-points from birth to late adolescence from 2,348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for nonlinear change and inter-individual variation in nonlinear trajectories was somewhat less common (11% and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. By contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often nonlinear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • added supplementary files

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted June 12, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Epigenome-wide change and variation in DNA methylation from birth to late adolescence
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Epigenome-wide change and variation in DNA methylation from birth to late adolescence
Rosa H. Mulder, Alexander Neumann, Charlotte A. M. Cecil, Esther Walton, Lotte C. Houtepen, Andrew J. Simpkin, Jolien Rijlaarsdam, Bastiaan T. Heijmans, Tom R. Gaunt, Janine F. Felix, Vincent W. V. Jaddoe, Marian J. Bakermans-Kranenburg, Henning Tiemeier, Caroline L. Relton, Marinus H. van IJzendoorn, Matthew Suderman
bioRxiv 2020.06.09.142620; doi: https://doi.org/10.1101/2020.06.09.142620
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Epigenome-wide change and variation in DNA methylation from birth to late adolescence
Rosa H. Mulder, Alexander Neumann, Charlotte A. M. Cecil, Esther Walton, Lotte C. Houtepen, Andrew J. Simpkin, Jolien Rijlaarsdam, Bastiaan T. Heijmans, Tom R. Gaunt, Janine F. Felix, Vincent W. V. Jaddoe, Marian J. Bakermans-Kranenburg, Henning Tiemeier, Caroline L. Relton, Marinus H. van IJzendoorn, Matthew Suderman
bioRxiv 2020.06.09.142620; doi: https://doi.org/10.1101/2020.06.09.142620

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (2517)
  • Biochemistry (4964)
  • Bioengineering (3469)
  • Bioinformatics (15181)
  • Biophysics (6885)
  • Cancer Biology (5380)
  • Cell Biology (7711)
  • Clinical Trials (138)
  • Developmental Biology (4518)
  • Ecology (7135)
  • Epidemiology (2059)
  • Evolutionary Biology (10210)
  • Genetics (7497)
  • Genomics (9767)
  • Immunology (4822)
  • Microbiology (13179)
  • Molecular Biology (5129)
  • Neuroscience (29367)
  • Paleontology (203)
  • Pathology (835)
  • Pharmacology and Toxicology (1460)
  • Physiology (2129)
  • Plant Biology (4734)
  • Scientific Communication and Education (1008)
  • Synthetic Biology (1337)
  • Systems Biology (4002)
  • Zoology (768)