Joint contribution of polygenic scores for depression and attention-deficit/hyperactivity disorder to youth suicidal ideation and attempt

Children presenting comorbid attention-deficit/hyperactivity disorder (ADHD) and depression symptoms have higher risks of later suicidal ideation and attempt. However, it is unclear to what extent this risk stems from individual differences in the genetic predisposition for ADHD and/or depression. We investigated the unique and combined contribution of genetic predisposition to ADHD and depression to suicidal ideation and attempt by early adulthood. Data were from two longitudinal population-based birth cohorts, the Quebec Longitudinal Study of Child Development and the Quebec Newborn Twin Study (total N = 1207). Genetic predisposition for ADHD and depression were measured using polygenic scores. Suicidal ideation and attempt by age 20 years were self-reported via questionnaires. Across the two cohorts, suicidal ideation and attempt were reported by 99 (8.2%) and 75 (6.1%) individuals, respectively. A higher polygenic score for depression was associated with significantly higher risk of suicidal ideation and attempt, while no significant associations were found for ADHD polygenic score. However, we found an interaction between polygenic scores for depression and ADHD in the association with suicide attempt (P = 0.012), but not suicidal ideation (P = 0.897). The association between polygenic score for depression and suicide attempt was significantly stronger for individuals with a higher polygenic score for ADHD. Individuals scoring >= 1-SD above the mean for both polygenic scores were at increased risk for suicide attempt compared to individuals with lower scores (OR 4.03, CI 1.64-9.90), as well as compared to individuals scoring >= 1-SD above the mean in only depression (OR 2.92, CI 1.01-8.50) or only ADHD (OR 4.88, CI 1.56-15.26) polygenic scores. Our findings suggest that genetic predisposition for ADHD and depression contributes to increase the risk of suicide attempt in a multiplicative, rather that additive, way. Our results contribute to our understanding of the etiology of suicide risk and may inform screening and risk stratification.