DNA methylation signature of childhood chronic physical aggression in T cells of both men and women.
BACKGROUND
High frequency of physical aggression is the central feature of severe conduct disorder and is associated with a wide range of social, mental and physical health problems. We have previously tested the hypothesis that differential DNA methylation signatures in peripheral T cells are associated with a chronic aggression trajectory in males. Despite the fact that sex differences appear to play a pivotal role in determining the development, magnitude and frequency of aggression, most of previous studies focused on males, so little is known about female chronic physical aggression. We therefore tested here whether or not there is a signature of physical aggression in female DNA methylation and, if there is, how it relates to the signature observed in males.


RESULTS
Methylation profiles were created using the method of methylated DNA immunoprecipitation (MeDIP) followed by microarray hybridization and statistical and bioinformatic analyses on T cell DNA obtained from adult women who were found to be on a chronic physical aggression trajectory (CPA) between 6 and 12 years of age compared to women who followed a normal physical aggression trajectory. We confirmed the existence of a well-defined, genome-wide signature of DNA methylation associated with chronic physical aggression in the peripheral T cells of adult females that includes many of the genes similarly associated with physical aggression in the same cell types of adult males.


CONCLUSIONS
This study in a small number of women presents preliminary evidence for a genome-wide variation in promoter DNA methylation that associates with CPA in women that warrant larger studies for further verification. A significant proportion of these associations were previously observed in men with CPA supporting the hypothesis that the epigenetic signature of early life aggression in females is composed of a component specific to females and another common to both males and females.
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada ; Research Unit on Children's Psycho-Social Maladjustment and Ste-Justine Hospital Research Center, University of Montreal, Montreal, Quebec, Canada ; Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec, Canada.
Claire
C
Guillemin
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada ; Research Unit on Children's Psycho-Social Maladjustment and Ste-Justine Hospital Research Center, University of Montreal, Montreal, Quebec, Canada ; Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec, Canada.
Nadine
N
Provençal
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.
Matthew
M
Suderman
Research Unit on Children's Psycho-Social Maladjustment and Ste-Justine Hospital Research Center, University of Montreal, Montreal, Quebec, Canada ; INSERM U669, Paris, France ; School of Social and Preventive Medicine, University of Montreal, Montreal, Quebec, Canada.
Sylvana M
SM
Côté
Research Unit on Children's Psycho-Social Maladjustment and Ste-Justine Hospital Research Center, University of Montreal, Montreal, Quebec, Canada ; School of Psycho-Education, University of Montreal, Montreal, Quebec, Canada.
Frank
F
Vitaro
McGill Centre for Bioinformatics, McGill University, Montreal, Quebec, Canada.
Michael
M
Hallett
Research Unit on Children's Psycho-Social Maladjustment and Ste-Justine Hospital Research Center, University of Montreal, Montreal, Quebec, Canada ; Department of Psychology and Pediatrics, University of Montreal, Montreal, Quebec, Canada ; School of Public Health and Population Sciences, University College Dublin, Dublin, Ireland ; INSERM U669, Paris, France.
Richard E
RE
Tremblay
Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada ; Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, Quebec, Canada.
Moshe
M
Szyf
D000328:Adult; D000374:Aggression / Q000523:psychology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002648:Child; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D059467:Transcriptome; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; C067133:corticotropin releasing factor-binding protein; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase