Genetic Association of Attention-Deficit/Hyperactivity Disorder and Major Depression With Suicidal Ideation and Attempts in Children: The Adolescent Brain Cognitive Development Study

Lee, Phil H.; Doyle, Alysa E.; Li, Xuyang; Silberstein, Micah; Jung, Jae-Yoon; Gollub, Randy L.; Nierenberg, Andrew A.; Liu, Richard T.; Kessler, Ronald C.; Perlis, Roy H.; Fava, Maurizio

doi:10.1016/j.biopsych.2021.11.026

Cited by 20 publications

(17 citation statements)

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“…This disparity is especially concerning in the field of youth suicide, where Black US youth are particularly vulnerable ( 2 , 24 ). Our findings extend recent ABCD Study results, showing associations of a depression polygenic risk score with suicide attempt in an analysis limited to European ancestry individuals ( 25 ) and a schizophrenia polygenic risk score with suicide attempt reported in the baseline ABCD Study assessment in admixed population with substantially fewer suicide attempt participants (64 vs. 182 in the current analysis) ( 26 ).…”

Section: Discussionsupporting

confidence: 89%

Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents

et al. 2022

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BackgroundAdolescent suicide is a major health problem in the US marked by a recent increase in risk of suicidal behavior among Black/African American youth. While genetic factors partly account for familial transmission of suicidal behavior, it is not clear whether polygenic risk scores of suicide attempt can contribute to suicide risk classification.ObjectivesTo evaluate the contribution of a polygenic risk score for suicide attempt (PRS-SA) in explaining variance in suicide attempt by early adolescence.MethodsWe studied N = 5,214 non-related youth of African and European genetic ancestry from the Adolescent Brain Cognitive Development (ABCD) Study (ages 8.9–13.8 years) who were evaluated between 2016 and 2021. Regression models tested associations between PRS-SA and parental history of suicide attempt/death with youth-reported suicide attempt. Covariates included age and sex.ResultsOver three waves of assessments, 182 youth (3.5%) reported a past suicide attempt, with Black youth reporting significantly more suicide attempts than their White counterparts (6.1 vs. 2.8%, p < 0.001). PRS-SA was associated with suicide attempt [odds ratio (OR) = 1.3, 95% confidence interval (CI) 1.1–1.5, p = 0.001]. Parental history of suicide attempt/death was also associated with youth suicide attempt (OR = 3.1, 95% CI, 2.0–4.7, p < 0.001). PRS-SA remained significantly associated with suicide attempt even when accounting for parental history (OR = 1.29, 95% CI = 1.1–1.5, p = 0.002). In European ancestry youth (n = 4,128), inclusion of PRS-SA in models containing parental history explained more variance in suicide attempt compared to models that included only parental history (ΔR2 = 0.7%, p = 0.009).ConclusionsFindings suggest that PRS-SA may be useful for youth suicide risk classification in addition to established risk factors.

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Section: Discussionsupporting

confidence: 89%

Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents

et al. 2022

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“…This disparity is especially concerning in the field of youth suicide, where Black US youth are particularly vulnerable (2,17). Our findings extend recent ABCD Study results showing associations of depression polygenic risk score with suicide attempt in an analysis limited to European ancestry (18) and schizophrenia polygenic risk score with suicide attempt reported in the baseline ABCD Study assessment in admixed population with substantially fewer suicide attempt participants (64 versus 182 in the current analysis) (19).…”

Section: Discussionsupporting

confidence: 88%

Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents

Barzilay

Visoki

Schultz

et al. 2022

Preprint

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Background: Adolescent suicide is a major health problem in the US marked by a recent increase in Black/African American youth suicide trends. While genetic factors partly account for familial transmission of suicidal behavior, it is not clear whether polygenic risk scores of suicide attempt have clinical utility in youth suicide risk classification. Objectives: To evaluate the contribution of a polygenic risk score for suicide attempt (PRS-SA) in explaining variance in suicide attempt by early adolescence. Methods: We studied N=5,214 non-related Black and White youth from the Adolescent Brain Cognitive Development (ABCD) Study (ages 8.9-13.8 years) who were evaluated between 2016 and 2021. Regression models tested associations between PRS-SA and parental history of suicide attempt/death with youth-reported suicide attempt. Covariates included age, sex, and race. Results: Over three waves of assessments, 182 youth (3.5%) reported a past suicide attempt, with Black youth reporting significantly more suicide attempts than their White counterparts (6.1% vs 2.8%, P<.001). PRS-SA was associated with suicide attempt (odds ratio [OR]=1.3, 95% confidence interval [CI] 1.1-1.5, P=.001). Inclusion of PRS-SA explained 2.7% of the variance in suicide attempts, significantly more than the base model including only age, sex and race, which explained 1.9% of the variance (P=.001). Parental history of suicide attempt/death was also associated with youth suicide attempt (OR=2.9, 95%CI 1.9-4.4, P<.001). Addition of PRS-SA to the model that included parental history significantly increased the variance explained from 3.3% to 4% (P=.002). Conclusions: Findings suggest that PRS-SA may be useful for suicide risk classification in diverse youth.

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“…An emerging body of work is deploying polygenic scores derived from adult GWAS samples in youth datasets (Daskalakis et al, 2021; Joo et al, 2022; Lee et al, 2021), as currently there are no large GWAS of SITB based in youth samples. These studies have identified significant associations between adult GWAS‐derived PRS for various traits and child SITB.…”

Section: Resultsmentioning

confidence: 99%

“…There is therefore potential in the literature for studies aiming to validate PRS of adult SITB in youth populations to determine if they explain a similar amount of variability in the youth SITB phenotypic outcomes. An interesting body of work is emerging testing adult‐based polygenic scores in child samples (Daskalakis et al, 2021; Joo et al, 2022; Lee et al, 2021); these studies have generally shown that adult‐based polygenic scores for complex traits such as psychiatric disorders do predict SITB outcomes in childhood, albeit weakly. However, none of these studies so far have tested polygenic scores for SITB and explained variance in children.…”

Section: Discussionmentioning

confidence: 99%

Genetics and epigenetics of self‐injurious thoughts and behaviors: Systematic review of the suicide literature and methodological considerations

Mirza

Docherty

Bakian

et al. 2022

American J of Med Genetics Pt B

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Suicide is a multifaceted and poorly understood clinical outcome, and there is an urgent need to advance research on its phenomenology and etiology. Epidemiological studies have demonstrated that suicidal behavior is heritable, suggesting that genetic and epigenetic information may serve as biomarkers for suicide risk. Here we systematically review the literature on genetic and epigenetic alterations observed in phenotypes across the full range of self-injurious thoughts and behaviors (SITB). We included 577 studies focused on genome-wide and epigenome-wide associations, candidate genes (SNP and methylation), noncoding RNAs, and histones. Convergence of specific genes is limited across units of analysis, although pathway-based analyses do indicate nervous system development and function and immunity/inflammation as potential underlying mechanisms of SITB. We provide suggestions for future work on the genetic and epigenetic correlates of SITB with a specific focus on measurement issues.

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Genetic Association of Attention-Deficit/Hyperactivity Disorder and Major Depression With Suicidal Ideation and Attempts in Children: The Adolescent Brain Cognitive Development Study

Cited by 20 publications

References 45 publications

Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents

Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents

Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents

Genetics and epigenetics of self‐injurious thoughts and behaviors: Systematic review of the suicide literature and methodological considerations

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