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.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Biol Psychiatry. 2022 Aug 1;92(3):236-245. doi: 10.1016/j.biopsych.2021.11.026. Epub 2021 Dec 22.
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.
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).
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) and in the follow-up year (odds ratio = 1.38, 95% CI = 1.08-1.77, p = 1.05 × 10), 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), suggesting a distinct contribution of the genetic risk underlying attention-deficit/hyperactivity disorder and depression on suicidal behaviors of children.
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.
自杀是儿童和青少年死亡的主要原因之一。众所周知,自杀的风险因素包括儿童期虐待、家庭冲突、社会逆境和精神病理学。虽然自杀风险也具有遗传性,但很少有研究调查年轻人的遗传风险。
使用多基因风险评分分析,我们研究了在参加 ABCD(青少年大脑认知发展)研究的 11878 名儿童中,主要精神疾病的遗传易感性是否与自杀行为有关。使用 Kiddie 情绪障碍和精神分裂症诊断与统计手册-5 青少年报告对自杀意念和自杀尝试数据进行评估。在对基因型数据进行稳健的质量控制后,我们将无亲缘关系的欧洲血统个体纳入分析(n=4344)。
在所研究的 8 种精神疾病中,抑郁多基因风险评分与终生自杀尝试均相关,在基线时(比值比=1.55,95%置信区间=1.10-2.18,p=1.27×10)和随访时(比值比=1.38,95%置信区间=1.08-1.77,p=1.05×10),调整了儿童的年龄、性别、社会经济背景、自杀家族史和精神病理学。相比之下,注意力缺陷/多动障碍多基因风险评分与终生自杀意念相关(比值比=1.15,95%置信区间=1.05-1.26,p=3.71×10),这表明注意力缺陷/多动障碍和抑郁的遗传风险对儿童自杀行为有独特的贡献。
美国儿童最大的自杀风险遗传样本表明,与注意力缺陷/多动障碍和抑郁相关的自杀风险具有显著的遗传基础。需要进一步研究,以检验是否纳入基因组风险可能有助于更有针对性的筛查和干预措施。