title: Association of childhood chronic physical aggression with a DNA methylation signature in adult human T cells.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Nadine
authors.initials: N
authors.lastname: Provençal
authors.affiliation: 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.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Suderman
authors.affiliation: 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.
authors.forename: Claire
authors.initials: C
authors.lastname: Guillemin
authors.affiliation: 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.
authors.forename: Frank
authors.initials: F
authors.lastname: Vitaro
authors.affiliation: 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.
authors.forename: Sylvana M
authors.initials: SM
authors.lastname: Côté
authors.affiliation: McGill Centre for Bioinformatics, McGill University, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallett
authors.affiliation: 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.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Tremblay
authors.affiliation: Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada; Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec, Canada.
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
mesh_terms: D000328:Adult; D000374:Aggression / Q000502:physiology*; D016022:Case-Control Studies; D002648:Child; D002877:Chromosomes, Human / Q000235:genetics; D016000:Cluster Analysis; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000378:metabolism*