Association of Childhood Chronic Physical Aggression with a DNA Methylation Signature in Adult Human T Cells

Abstract

BackgroundChronic 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.AimsTo test the hypothesis that a trajectory of chronic physical aggression during childhood is associated with a distinct DNA methylation profile during adulthood.MethodsWe 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.ResultsIn 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.ConclusionsThis 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.

The developmental origins of chronic physical aggression: biological pathways triggered by early life adversity

“…Indeed, in another study performed by our group, we observed similar DNA methylation signatures associated with childhood CPA in women (n=430 promoters) as seen in men, where 31 gene promoters were significantly associated in both sexes (Guillemin et al, 2014). Interestingly, a significant portion of this overlap is due to identical genomic sites being differentially methylated in a gender-independent fashion.…”

“…Moreover, these cytokines were also shown to be repressed in men with CPA compared with men on a normative developmental trajectory of aggressive behaviour (Provençal et al, 2013b). Interestingly, one of these downregulated cytokines in men with CPA, interleukin-6 (IL-6), was previously shown to be involved in aggressive behaviour in mice, because its knockout (IL-6 −/− ) resulted in an increased aggressive behaviour phenotype in these mice (Alleva et al, 1998).…”

Crime investigation through DNA methylation analysis: methods and applications in forensics

“…1b) (Day & Sweatt, 2010;Kovatsi et al, 2011;Provencal et al, 2014;Roth & Sweatt, 2010). The epigenetic factor, especially DNA methylation is the most important aspect of behavioral disorders with marked alteration in the DNA methylation pattern in the brain which leads to memory formation (Day & Sweatt, 2010).…”

Le nouveau paradigme de l’origine développementale de la santé et des maladies (DOHaD)

“…Ces soins modifient, dans l'hippocampe, l'épigénome d'un gène clé, celui qui code le récepteur aux glucocorticoïdes, mais également l'épigénome de réseaux de gènes [4]. Des mécanismes semblables opèrent chez le rongeur, le macaque et l'humain [5,6], montrant la conservation entre les espèces des mécanismes impliqués dans de tels processus d'adaptation à l'environnement. Des mécanismes épigéné-tiques ont depuis été impliqués dans les effets, sur la progéniture, de divers stimulus environnementaux subis à différents stades par la mère ou par le père : nutrition déséquilibrée, adversité, stress, peur du prédateur, défaite sociale, etc.…”

“…Des mécanismes épigéné-tiques ont depuis été impliqués dans les effets, sur la progéniture, de divers stimulus environnementaux subis à différents stades par la mère ou par le père : nutrition déséquilibrée, adversité, stress, peur du prédateur, défaite sociale, etc. [5,[7][8][9][10][11][12]] (➜). …”