Glucocorticoid receptor gene (NR3C1) is hypermethylated in adult males with aggressive behaviour

Aggressive behaviour is a serious threat to the personal safety and property of others due to the potential that the assailant may hurt people, himself/herself or objects, and aggression has always been one of the focuses of research and concern. Accumulating evidence suggests that the hypothalamic-pituitary-adrenal (HPA) axis plays a major role in the development, elicitation, enhancement and genetic susceptibility of aggressive behaviour in humans and animals. GR (NR3C1) plays a crucial role in controlling HPA activity, which directly affects aggressive behaviour. Here, we investigated the methylation state of the NR3C1 gene promoter region and its role in aggressive behaviour in adult males for the first time by applying a case-control approach (N = 106 controls, N = 104 patients). Methylation of NR3C1 was measured in peripheral blood samples at exons 1_D, 1_B and 1_F via sodium bisulfite treatment combined with the MethylTarget method. Methylation of the NR3C1 gene was significantly correlated with aggressive behaviour, and the methylation levels of 1_D, 1_B and 1_F were upregulated in the aggressive behaviour group, intentional injury subgroup and robbery subgroup, and the significance varied. In addition, multiple CpG sites were found to be significantly associated with aggressive behaviour. These results suggest that epigenetic aberrations of NR3C1 are associated with aggressive behaviour, and epigenetic processes might mediate aggressive behaviour by affecting the activity of the HPA axis. This correlative study between DNA methylation of the NR3C1 gene and aggressive behaviour in patients may be helpful for forensic assessments.