Genome-wide Polygenic Scores for Multiple Psychiatric and Common Traits Identify Preadolescent Youth with Risk for Suicide

Importance. Suicide is the second leading cause of death in children worldwide but no available means exist to identify the risk in youth. Objective. To predict the risk of suicide in children and to investigate whether and to what extents genetic factors and a major environmental risk factor, early life stress(ELS), influence youth suicide. Design, Setting and Participants. We analyzed the genotype-phenotype data of 11,869 preadolescent children ages 9- to 10-year-old from the Adolescent Brain and Cognitive Development (ABCD) study. We estimated genome-wide polygenic scores (GPSs) of 25 complex traits to investigate their phenome-wide associations and predictive utility with suicidality (suicidal ideation and attempt) with machine learning approaches. Predictors. GPSs of 25 traits including psychiatric disorders, personality, cognitive capacity, and psychological traits. Parent Child Behavior Checklist to measure ELS in youth and Youth Family Environment Scale to assess family environment. Main outcomes and Measures. Records of suicidal ideation and attempt of the participants were derived from the computerized version of Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Results. We identified three GPSs associated with youth suicidality in multiethnic (n = 7,206) and European-ancestry (n = 5,749) participants: ADHD (P = 3.48x10− 4; odds ratio = 1.13 in multiethnic participants, P = 5.60x10− 5, OR = 1.25 in European-ancestry participants), general happiness (P = 1.43x10− 3; OR = 0.89 in multiethnic, P = 8.61x10− 4, OR = 0.89 in European) and autism spectrum disorder(ASD) (P = 1.81x10− 3; OR = 1.15 in multiethnic, P = 1.26x10− 3, OR = 1.18 in European). We also found a significant GPS-by-environment interaction between the effects of genetic risk factors for ASD and the level of ELS in increasing the risk for suicidal ideation (P = 1.36x10− 2, OR = 1.12 in multiethnic, P = 1.39x10− 3, OR = 1.19 in European). A machine learning model trained on the same data showed moderately accurate prediction of children with overall suicidal ideation with a test ROC-AUC of 0.727 (0.746 in European), and with suicidal attempts with a test ROC-AUC of 0.641 (0.975 in European) in held-out samples. Conclusions and Relevance. This study provides the first quantitative account of polygenic and environmental factors of suicidality in a large, representative population of preadolescent youth. It thus shows the potential utility of the GPSs in identifying a child with high risk for suicidality for early screening, intervention, and prevention.

Genome-wide Polygenic Scores for Multiple Psychiatric and Common Traits Identify Preadolescent Youth with Risk for Suicide

Suicide is a leading cause of death in youth worldwide, but identifying which youth are at high risk for suicide remains challenging. We constructed genome-wide polygenic scores (GPSs) from 24 psychiatric disorders and common traits from 8,212 US preadolescent children ages 9 to 10 and investigated their associations and predictive utility with suicidality (suicidal ideation and attempt). We identified three GPSs significantly associated with youth suicidality: ADHD (P=2.83x10-4; odds ratio=1.12), general happiness with a belief that life is meaningful (P=1.30x10-3; odds ratio=0.89) and autism spectrum disorder (ASD) (P=1.81x10-3; odds ratio=1.14). We also found a significant gene-by-environment interaction such that the GPS of ASD in the context of early life stress substantially increased suicidal ideation (P=1.39x10-2, odds ratio=1.11). Machine learning models showed, in predicting suicidal ideation, a receiver operators characteristics-area under the curve (ROC-AUC) of 0.72, and, in suicidal attempts, a ROC-AUC of 0.765. By providing the first quantitative account of the polygenic and environmental factors of suicidality in a large, representative population of preadolescent youth, this study shows the potential utility of the GPSs in investigating youth suicidality for early screening, intervention, and prevention.

The Impact of Children's Temperament on How Parents Resolve Safety Disagreements During Preadolescence

Objectives Parents play an important role in keeping their children safe. However, this becomes more difficult during preadolescence as children seek greater autonomy away from the direct supervision of adults. The current study focused on preadolescent youth (10–13 years) and examined parent–child disagreements about safety, with a focus on determining if child temperament attributes moderate the relation between how parents learn of these and resolve these disagreements. Methods A short-term longitudinal design was used. Parents and children retrospectively recalled safety disagreements together and then independently completed questionnaires about these. Parents then tracked disagreements over 1 month. Results The behavioral attributes of inhibitory control and risk-taking propensity both moderated the relationships between parental source of knowledge of safety disagreements and subsequent methods of resolution. Conclusion Safety-promotion messaging for parents of preadolescents may need to be tailored based on child attributes to maximize effectiveness.

Assessing callous-unemotional traits: development of a brief, reliable measure in a large and diverse sample of preadolescent youth

BackgroundCallous-unemotional (CU) traits are critical to developmental, diagnostic, and clinical models of antisocial behaviors (AB). However, assessments of CU traits within large-scale longitudinal and neurobiologically focused investigations remain remarkably sparse. We sought to develop a brief measure of CU traits using items from widely administered instruments that could be linked to neuroimaging, genetic, and environmental data within already existing datasets and future studies.MethodsData came from a large and diverse sample (n = 4525) of youth (ages~9–11) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study. Moderated nonlinear factor analysis was used to assess measurement invariance across sex, race, and age. We explored whether CU traits were distinct from other indicators of AB, investigated unique links with theoretically-relevant outcomes, and replicated findings in an independent sample.ResultsThe brief CU traits measure demonstrated strong psychometric properties and evidence of measurement invariance across sex, race, and age. On average, boys endorsed higher levels of CU traits than girls and CU traits were related to, yet distinguishable from other indicators of AB. The CU traits construct also exhibited expected associations with theoretically important outcomes. Study findings were also replicated across an independent sample of youth.ConclusionsIn a large, multi-site study, a brief measure of CU traits can be measured distinctly from other dimensions of AB. This measure provides the scientific community with a method to assess CU traits in the ABCD sample, as well as in other studies that may benefit from a brief assessment of CU.