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PLoS One. 2014 Apr 1;9(4):e89839. doi: 10.1371/journal.pone.0089839. eCollection 2014.

Association of childhood chronic physical aggression with a DNA methylation signature in adult human T cells.

Author information

1
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada; Research Unit on Children's Psycho-Social Maladjustment and Sainte-Justine Hospital Research Center, University of Montreal, Montreal, Canada; Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec, Canada.
2
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada; Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec, Canada; McGill Centre for Bioinformatics, McGill University, Montreal, Quebec, Canada.
3
Research Unit on Children's Psycho-Social Maladjustment and Sainte-Justine Hospital Research Center, University of Montreal, Montreal, Canada; School of Psycho-Education, University of Montreal, Montréal, Quebec, Canada.
4
Research Unit on Children's Psycho-Social Maladjustment and Sainte-Justine Hospital Research Center, University of Montreal, Montreal, Canada; School of Social and Preventive Medicine, University of Montreal, Montréal, Quebec, Canada.
5
McGill Centre for Bioinformatics, McGill University, Montreal, Quebec, Canada.
6
Research Unit on Children's Psycho-Social Maladjustment and Sainte-Justine Hospital Research Center, University of Montreal, Montreal, Canada; Department of Psychology and Pediatrics, University of Montreal, Montreal, Quebec, Canada; School of Public Health, Physiotherapy and Population Sciences, University College Dublin, Dublin, Ireland.
7
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada; Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec, Canada.

Abstract

BACKGROUND:

Chronic physical aggression (CPA) is characterized by frequent use of physical aggression from early childhood to adolescence. Observed in approximately 5% of males, CPA is associated with early childhood adverse environments and long-term negative consequences. Alterations in DNA methylation, a covalent modification of DNA that regulates genome function, have been associated with early childhood adversity.

AIMS:

To test the hypothesis that a trajectory of chronic physical aggression during childhood is associated with a distinct DNA methylation profile during adulthood.

METHODS:

We analyzed genome-wide promoter DNA methylation profiles of T cells from two groups of adult males assessed annually for frequency of physical aggression between 6 and 15 years of age: a group with CPA and a control group. Methylation profiles covering the promoter regions of 20 000 genes and 400 microRNAs were generated using MeDIP followed by hybridization to microarrays.

RESULTS:

In total, 448 distinct gene promoters were differentially methylated in CPA. Functionally, many of these genes have previously been shown to play a role in aggression and were enriched in biological pathways affected by behavior. Their locations in the genome tended to form clusters spanning millions of bases in the genome.

CONCLUSIONS:

This study provides evidence of clustered and genome-wide variation in promoter DNA methylation in young adults that associates with a history of chronic physical aggression from 6 to 15 years of age. However, longitudinal studies of methylation during early childhood will be necessary to determine if and how this methylation variation in T cells DNA plays a role in early development of chronic physical aggression.

PMID:
24691403
PMCID:
PMC3972178
DOI:
10.1371/journal.pone.0089839
[Indexed for MEDLINE]
Free PMC Article
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