Medical Student University of Toronto, Temerty Faculty of Medicine, United States
Background: Youth suicide is one of the leading causes of death among children in Canada and worldwide. Suicide accounted for up to 25% of all deaths among 15–24-year-old youth, making it a major global health concern. Although suicide ideation can be a major determinant of suicide risk, ideation does not always correlate with suicide attempts.
Suicide attempt consists of multifactorial risk factors where both genetic and environmental factors can increase the risk of the behaviour. A recent large-scale genetic study reported that genetic underpinnings, more specifically a region on chromosome 7 with DNA variations, significantly predicted suicide attempts in adults. Although the influence of genetics on behaviour can change between children and adults, studies that examine genetics underlying youth suicide are limited.
Objective: This study aims to examine the genetics underlying youth suicide attempts compared to ideation in a large sample of European youth through a genome-wide association study.
Design/Methods: 3594 children were recruited as part of the Adolescent Brain Cognitive Development (ABCD) study. The sample was genotyped for GWAS with the Smokescreen® Genotyping Array. All participants were of European ancestry as determined by principal component analysis. Standard individual and SNP variant quality control procedures were performed using PLINK and R statistical software.
Suicidal ideation for each child was evaluated using self-reported Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5 (KSADS-5) at baseline (age=9.92,SD=0.62). Youths who self-reported suicidal attempts in the present or past were categorized as cases. Youth who self-reported suicidal ideation in the present or past were categorized as controls.
Genome-wide association study for youth suicidal ideation was performed using PLINK and the graphs were created using R. Sex and 10 ancestry-informative principal components were used as covariates.
Results: Youth with suicidal attempts significantly had different genetic variants in a genome-wide level compared to youth with suicidal ideation. Two SNP variants exceeded the genome-wide significant threshold (p < 5 ×10e−8). The top-hit marker was on chromosome 19, rs112459553, an intron variant of the ZNF586 (Zinc Finger Protein 586) gene (p = 4.67e-09). The following top hits were also on chromosome 19, including rs76439307 from ZSCAN4 (Zinc Finger and SCAN Domain Containing 4) gene and rs113409189 from ZNF530 (Zinc Finger Protein 530) gene. The top-hit genes were mainly expressed in nervous system development and transcription (gene expression) pathways.
Conclusion(s): The results propose that genes in nervous system development and in transcription pathways may be involved in youth suicidal attempts. These results emphasize the importance of considering genetics underlying youth suicidal behaviour when assessing at-risk youth for suicide. They may serve as a base for precision medicine, developing novel early personalized prevention and treatment techniques for suicide attempts based on genetic risk factors. While the large size of the ABCD sample provides increased power, focus on the European sub-sample reduces the generalizability of the results to other ethnicities. Future studies with diverse ethnicities are required.
