Genetic influences on suicide attempt in adolescence: Evaluating mediation by impulsivity and painful and provocative events

Background: Genetic risk factors, impulsivity, and exposure to painful and provocative events (PPEs) have each been linked with risk for suicide attempt (SA). However, the degree to which genetic associations with SA are mediated by dimensions of impulsivity and PPEs remains unexplored, particularly in early adolescence. Methods: Participants were 6,402 individuals (52.0% male, 48.0% female, 72.3% European ancestry, 27.7% African ancestry, mean age at baseline = 9.47 years) from the Adolescent Brain Cognitive Development (ABCD) Study. Genetic liability for SA was measured using polygenic scores and family history density scores. Multiple dimensions of impulsivity were assessed using self-report measures and laboratory tasks, and potential PPEs included injuries, traumatic events, non-suicidal self-injury, and operations. A series of mediation models was specified to evaluate whether genetic associations with SA risk were mediated by impulsivity and PPE exposure. Separate models were tested in adolescents of European and African ancestry. Sex, age, and socioeconomic factors were included as covariates.Results: Genetic liability for SA was largely unrelated to impulsivity, PPE exposure, and SA risk. In addition, there was little support for the hypothesis that more impulsive individuals are more likely to experience PPEs, with the exception that urgency and low conscientiousness were significantly related to non-suicidal self-injury, and sensation-seeking was associated with exposure to traumatic events in adolescents of African ancestry. Several dimensions of impulsivity and two PPEs (non-suicidal self-injury and traumatic events) were related to increased risk for SA.Conclusions: Impulsivity and PPEs each contribute to risk for SA. However, there is little support for the hypothesis that genetic influences on SA are mediated by impulsivity and PPE exposure in early adolescence.