Phil H Lee1, Alysa E Doyle2, Xuyang Li3, Micah Silberstein3, Jae-Yoon Jung4, Randy L Gollub5, Andrew A Nierenberg6, Richard T Liu7, Ronald C Kessler8, Roy H Perlis9, Maurizio Fava10. 1. Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts. Electronic address: PLEE0@mgh.harvard.edu. 2. Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 3. Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts. 4. Department of Pediatrics, Stanford University, Stanford, California. 5. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 6. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital, Boston, Massachusetts. 7. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Depression Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts. 8. Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts. 9. Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts. 10. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Abstract
BACKGROUND: Suicide is among the leading causes of death in children and adolescents. There are well-known risk factors of suicide, including childhood abuse, family conflicts, social adversity, and psychopathology. While suicide risk is also known to be heritable, few studies have investigated genetic risk in younger individuals. METHODS: Using polygenic risk score analysis, we examined whether genetic susceptibility to major psychiatric disorders is associated with suicidal behaviors among 11,878 children enrolled in the ABCD (Adolescent Brain Cognitive Development) Study. Suicidal ideation and suicide attempt data were assessed using the youth report of the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5. After performing robust quality control of genotype data, unrelated individuals of European descent were included in analyses (n = 4344). RESULTS: Among 8 psychiatric disorders we examined, depression polygenic risk scores were associated with lifetime suicide attempts both in the baseline (odds ratio = 1.55, 95% CI = 1.10-2.18, p = 1.27 × 10-2) and in the follow-up year (odds ratio = 1.38, 95% CI = 1.08-1.77, p = 1.05 × 10-2), after adjusting for children's age, sex, socioeconomic backgrounds, family history of suicide, and psychopathology. In contrast, attention-deficit/hyperactivity disorder polygenic risk scores were associated with lifetime suicidal ideation (odds ratio = 1.15, 95% CI = 1.05-1.26, p = 3.71 × 10-3), suggesting a distinct contribution of the genetic risk underlying attention-deficit/hyperactivity disorder and depression on suicidal behaviors of children. CONCLUSIONS: The largest genetic sample of suicide risk data in U.S. children suggests a significant genetic basis of suicide risk related to attention-deficit/hyperactivity disorder and depression. Further research is warranted to examine whether incorporation of genomic risk may facilitate more targeted screening and intervention efforts.
BACKGROUND: Suicide is among the leading causes of death in children and adolescents. There are well-known risk factors of suicide, including childhood abuse, family conflicts, social adversity, and psychopathology. While suicide risk is also known to be heritable, few studies have investigated genetic risk in younger individuals. METHODS: Using polygenic risk score analysis, we examined whether genetic susceptibility to major psychiatric disorders is associated with suicidal behaviors among 11,878 children enrolled in the ABCD (Adolescent Brain Cognitive Development) Study. Suicidal ideation and suicide attempt data were assessed using the youth report of the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5. After performing robust quality control of genotype data, unrelated individuals of European descent were included in analyses (n = 4344). RESULTS: Among 8 psychiatric disorders we examined, depression polygenic risk scores were associated with lifetime suicide attempts both in the baseline (odds ratio = 1.55, 95% CI = 1.10-2.18, p = 1.27 × 10-2) and in the follow-up year (odds ratio = 1.38, 95% CI = 1.08-1.77, p = 1.05 × 10-2), after adjusting for children's age, sex, socioeconomic backgrounds, family history of suicide, and psychopathology. In contrast, attention-deficit/hyperactivity disorder polygenic risk scores were associated with lifetime suicidal ideation (odds ratio = 1.15, 95% CI = 1.05-1.26, p = 3.71 × 10-3), suggesting a distinct contribution of the genetic risk underlying attention-deficit/hyperactivity disorder and depression on suicidal behaviors of children. CONCLUSIONS: The largest genetic sample of suicide risk data in U.S. children suggests a significant genetic basis of suicide risk related to attention-deficit/hyperactivity disorder and depression. Further research is warranted to examine whether incorporation of genomic risk may facilitate more targeted screening and intervention efforts.
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