Genome-wide polygenic scores may identify suicidality risk in children

A genomic approach may help identify children at high risk for suicidal thoughts and behaviors, according to results of a cohort study published in JAMA Network Open.

“Genetic predisposition to suicidal behaviors has been reported to interact with environmental factors such as early life stress, potentially via epigenetic mechanisms,” Yoonjung Yoonie Joo, PhD, of the department of psychology at Seoul National University in the Republic of Korea, and colleagues wrote.

“Investigating whether and to what extent early life stress and genetic factors act synergistically on suicidal thoughts and behaviors among youths will offer needed insight into the biological factors associated with suicide and may provide actionable targets for intervention,” they added. “However, to our knowledge, no studies have investigated the interaction between genetic and environmental factors or the utility of genetic factors for predicting suicidal thoughts and behaviors among youths.”

Joo and colleagues sought to examine potential associations between genome-wide polygenic scores for psychiatric and common traits and risk for suicide among preadolescent children, as well as the role of early life stress and polygenic factors in youth suicidal thoughts and behaviors. They analyzed genotype-phenotype data from 11,869 children aged 9 to 10 years who participated in the Adolescent Brain and Cognitive Development study, with data collection between Sept. 1, 2016, and Oct. 21, 2018. They used machine learning approaches to estimate genome-wide polygenic scores of 24 complex traits and examine their phenome-wide associations and utility for risk assessment of suicidal thoughts and behaviors. Further, they used the Child Behavior Checklist to measure early life stress and the Family Environment Scale to examine family environment, as well as the Kiddie Schedule for Affective Disorders and Schizophrenia to derive suicidal ideation and suicide attempts.

Complete data for phenotypic outcomes, genotypes and covariates were available from 7,140 participants in the multiethnic cohort (mean age, 9.9 years; 50.3% girls), of whom 925 had suicidal ideation and 63 suicide attempts. A total of 729 had African ancestry, 276 had mixed American ancestry, 150 had East Asian ancestry, 5,718 had European ancestry and 267 had other ancestries. Results showed significant associations between three genome-wide polygenic scores and suicidal thoughts and behaviors among all participants. These were ADHD (OR = 1.12; 95% CI, 1.05-1.21), schizophrenia (OR = 1.5; 95% CI, 1.17-1.93) and general happiness (OR = 0.89; 95% CI, 0.83-0.96). When researchers analyzed only children with European ancestry, they noted associations between three additional genome-wide polygenic scores with false discovery rate significance and suicidal thoughts and behaviors. These were autism spectrum disorder (OR = 1.18; 95% CI, 1.06-1.31), major depressive disorder (OR = 1.12; 95% CI, 1.04-1.21) and PTSD (OR = 1.12; 95% CI, 1.04-1.21).

Results also showed a significant relationship between genome-wide polygenic scores and environment, with genetic risk factors for ASD and the level of early life stress linked to increased risk for overall suicidal ideation and overall suicidal thoughts and behaviors (OR = 1.2; 95% CI, 1.07-1.35). A machine learning model that incorporated multi-trait genome-wide polygenic scores and additional self-reported questionnaire data resulted in an estimate with moderate accuracy for overall suicidal thoughts and behaviors and suicidal ideation among children with European ancestry only. The integrated model outperformed the baseline model for estimating the risk for overall suicidal thoughts and behaviors and suicidal ideation among all children in the multiethnic cohort.

“These results highlight the importance and potential utility of the genome-wide polygenic score approach to early screening for high risk of suicidal behaviors among pediatric populations,” Joo and colleagues wrote. “The study’s findings may also motivate further development of genome-wide polygenic score–based screening methods and intervention strategies for youths at risk for suicide. With the integrative model developed in this study, suicide prevention programs could further tailor strategies to subgroups with distinct risk profiles, such as children with high polygenic scores for particular traits or children with high genetic vulnerability to early life stress, which may improve suicide intervention and prevention strategies for youths.”