Mediation of DNA methylation (cg04622888 and cg05037505) in the association between childhood maltreatment and non-suicidal self-injury in early adolescents.

It is unclear whether DNA methylation underlies the association between childhood maltreatment (CM) and non-suicidal self-injury (NSSI) in early adolescents. We aim to explore the mediation of specific DNA methylation sites in the associations of CM and its subtypes with NSSI, following investigation on the association between specific DNA methylation sites and NSSI. A case-control study was conducted to examine 155 adolescents aged 12-14 years who were identified to have engaged in NSSI and 201 controls. CM and its subtypes were evaluated by using the Childhood Trauma Questionnaire. The EPIC 850 k Bead Chip was used to discover differential methylation sites (DMSs) in the peripheral blood between 10 NSSI cases and 10 controls. Targeted pyrosequencing was employed to detect the levels of specific DMSs among the total study population, which were selected based on bioinformatics analyses and literature review. We discovered 456 DMSs between NSSI cases and controls, 219 were hypermethylated and 237 were hypomethylated. After controlling for potential confounders, CM or its subtypes, and the methylation of cg04622888 and cg05037505 were all significantly associated with NSSI (all P < 0.05). The total association of CM and its subtypes with NSSI were all significantly (all P < 0.05), with the standardized coefficient (β) ranged from 0.12 for physical neglect to 0.24 for emotional neglect and CM. Significant indirect association of physical neglect with NSSI through methylation of cg04622888 was observed and the mediating proportion was 0.14 (95%CI 0.06-0.23). Significant indirect associations of emotional abuse, emotional neglect, and physical neglect with NSSI through methylation of cg05037505 were also observed, and the mediating proportions were 0.09 (95%CI 0.04-0.14), 0.08 (95%CI, 0.03-0.14) and 0.19 (95%CI 0.07-0.32), respectively. Data of this study suggested that methylation of cg04622888 and cg05037505 were independently associated with NSSI among early adolescents, and they partially mediated the associations of emotional abuse, emotional neglect, and physical abuse with NSSI.