Childhood maltreatment, polygenic risk score, and risk of self-injurious thoughts and behaviors in early adolescents: a cohort study

Although childhood maltreatment (CM) and genetic risk have both been associated with self-injurious thoughts and behaviors (SITBs), their combined effects on non-suicidal self-injury (NSSI), suicidal ideation (SI), and suicide attempts (SA) remain unclear. A total of 1402 Chinese adolescents aged 11 to 15 years at baseline of the Chinese Adolescent Healthy Growth Cohort were examined. CM, NSSI, SI and SA were assessed by valid questionnaire at baseline survey and two rounds of annual follow-up survey. Polygenic risk score (PRS) for SITBs was calculated by weighted accumulation effects of 48 alleles identified in the East Asia population. Poisson generalized linear models were employed to estimate the independent and joint association of CM and PRS with NSSI, SI and SA. CM was significantly associated with NSSI (adjusted relative risk [aRR], 1.61; 95% confidence interval [95%CI], 1.15–2.25), SI (aRR, 1.38; 95%CI, 1.05–1.81) and SA (aRR, 2.02; 95%CI, 1.16–3.51), while per standard deviation [SD] increase in PRS was only associated with NSSI (aRR, 1.21; 95%CI, 1.06–1.39). The combined associations of CM and PRS with NSSI, SI, and SA were comparable to the sum of the risks associated with each factor individually. CM was independently associated with increased risks of NSSI, SI, and SA, whereas PRS was associated only with NSSI. No significant multiplicative or additive interactions were observed between CM and PRS. Given the limited candidate variants comprising the PRS, these findings warrant cautious interpretation and validation using genome-wide data.