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

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Abstract

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 1D, 1B and 1F 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 1D, 1B and 1F 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.

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Acknowledgements

We are also grateful to the Center for Genetic & Genomic Analysis, Genesky Biotechnologies Inc. (Shanghai, 201315) for their technical support in methylation sequencing.

Funding

This work was supported by the National Natural Science Foundation of China under grant 31660310 and 31860300; the Joint Special Funds for the Department of Science and Technology of Yunnan Province-Kunming Medical University under grant number 2017FE467(-022) and 2018FE001(-131); the Yunnan Provincial Young Academic and Technical Leader Reserve Talent Project under grant number 2018HB104; the Hundred-Talent Program of Kunming Medical University under grant 60117190447; the Science and Technology Innovation Group of Kunming Medical University under grant number CXTD201803; the Key Laboratory of Forensic Genetics of Ministry of Public Security, Institute of Forensic Science under grant number 2018FGKFKT03 and the State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University under grant number 2017KF002. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

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  1. Linlin Liu and Jiajue Li contributed equally to this work.

Authors and Affiliations

  1. School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China

    Linlin Liu, Jiajue Li, Lili Qing, Ming Yan, Gen Xiong, Xinqing Lian, Liping Hu & Shengjie Nie

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  1. Linlin Liu
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Contributions

Shengjie Nie and Liping Hu carried out the study conception and design. Liping Hu, Ming Yan and Jiajue Li performed sample collection and material preparation. Linlin Liu, Jiajue Li, Gen Xiong and Xinqing Lian carried out data acquisition and analysis. Linlin Liu and Lili Qing drafted the manuscript. Shengjie Nie performed manuscript review. All authors read and approved the final manuscript.

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Correspondence to Liping Hu or Shengjie Nie.

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Approval was obtained from the ethics committee of Kunming Medical University. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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Table S1

DNA methylation levels of NR3C1 promoters 1D, 1B and 1F in aggressive behaviour patients and matched healthy controls (XLSX 10 kb)

Table S2

All CpG sites methylation in patients with robbery and healthy controls (XLSX 29 kb)

Table S3

CpG sites with significant differences in methylation between aggressive behaviour patients and matched healthy controls (XLSX 12 kb)

Table S4

All CpG sites methylation in patients with Intentional injury and robbery (XLSX 15.5 kb)

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Liu, L., Li, J., Qing, L. et al. Glucocorticoid receptor gene (NR3C1) is hypermethylated in adult males with aggressive behaviour. Int J Legal Med 135, 43–51 (2021). https://doi.org/10.1007/s00414-020-02328-7

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  • DOI: https://doi.org/10.1007/s00414-020-02328-7

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