Citation

Provençal N, Suderman MJ, Guillemin C, Vitaro F, Côté SM, Hallett M, Tremblay RE, Szyf M. PLoS One 2014; 9(4): e89839.

Affiliation

Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada; Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec, Canada.

Copyright

(Copyright © 2014, Public Library of Science)

DOI

10.1371/journal.pone.0089839

PMID

24691403

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.

Language: en