Dataset Information

Polygenic Contributions to Suicidal Thoughts and Behaviors in a Sample Ascertained for Alcohol Use Disorders.

ABSTRACT:

Introduction

Suicidal thoughts and behaviors have partially distinct genetic etiologies.

Methods

We used PRS-CS to create polygenic risk scores (PRSs) from GWAS of non-suicidal self-injury, broad-sense self-harm ideation, nonfatal suicide attempt, death by suicide, and depression. Using mixed-effect models, we estimated whether these PRSs were associated with a range of suicidal thoughts and behaviors in the Collaborative Study on the Genetics of Alcoholism (N = 7,526).

Results

All PRSs were significantly associated with suicidal ideation and suicide attempt (betas = 0.08-0.44, false discovery rate [FDR] <0.023). All PRSs except non-suicidal self-injury PRS were associated with active suicidal ideation (betas = 0.14-0.22, FDR <0.003). Several associations remained significant in models where all significant PRSs were included as simultaneous predictors, and when all PRSs predicted suicide attempt, the PRS together explained 6.2% of the variance in suicide attempt. Significant associations were also observed between some PRSs and persistent suicidal ideation, non-suicidal self-injury, compounded suicide attempt, and desire to die.

Conclusion

Our findings suggest that PRS for depression does not explain the entirety of the variance in suicidal thoughts and behaviors, with PRS specifically for suicidal thoughts and behaviors making additional and sometimes unique contributions.

SUBMITTER: Colbert SMC

PROVIDER: S-EPMC10697665 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

Polygenic Contributions to Suicidal Thoughts and Behaviors in a Sample Ascertained for Alcohol Use Disorders.

Colbert Sarah M C SMC Mullins Niamh N Chan Grace G Meyers Jacquelyn L JL Schulman Jessica J Kuperman Samuel S Lai Dongbing D Nurnberger John J Plawecki Martin H MH Kamarajan Chella C Anokhin Andrey P AP Bucholz Kathleen K KK Hesselbrock Victor V Edenberg Howard J HJ Kramer John J Dick Danielle M DM Porjesz Bernice B Agrawal Arpana A Johnson Emma C EC

Complex psychiatry 20230118 1-4

<h4>Introduction</h4>Suicidal thoughts and behaviors have partially distinct genetic etiologies.<h4>Methods</h4>We used PRS-CS to create polygenic risk scores (PRSs) from GWAS of non-suicidal self-injury, broad-sense self-harm ideation, nonfatal suicide attempt, death by suicide, and depression. Using mixed-effect models, we estimated whether these PRSs were associated with a range of suicidal thoughts and behaviors in the Collaborative Study on the Genetics of Alcoholism (<i>N</i> = 7,526).<h4> ...[more]

PMID: 38058956

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Project description:American Indians (AI) demonstrate the highest rates of both suicidal behaviors (SB) and alcohol use disorders (AUD) among all ethnic groups in the US. Rates of suicide and AUD vary substantially between tribal groups and across different geographical regions, underscoring a need to delineate more specific risk and resilience factors. Using data from over 740 AI living within eight contiguous reservations, we assessed genetic risk factors for SB by investigating: (1) possible genetic overlap with AUD, and (2) impacts of rare and low frequency genomic variants. Suicidal behaviors included lifetime history of suicidal thoughts and acts, including verified suicide deaths, scored using a ranking variable for the SB phenotype (range 0-4). We identified five loci significantly associated with SB and AUD, two of which are intergenic and three intronic on genes AACSP1 , ANK1 , and FBXO11 . Nonsynonymous rare mutations in four genes including SERPINF1 (PEDF), ZNF30 , CD34 , and SLC5A9 , and non-intronic rare mutations in genes OPRD1 , HSD17B3 and one lincRNA were significantly associated with SB. One identified pathway related to hypoxia-inducible factor (HIF) regulation, whose 83 nonsynonymous rare variants on 10 genes were significantly linked to SB as well. Four additional genes, and two pathways related to vasopressin-regulated water metabolism and cellular hexose transport, also were strongly associated with SB. This study represents the first investigation of genetic factors for SB in an American Indian population that has high risk for suicide. Our study suggests that bivariate association analysis between comorbid disorders can increase statistical power; and rare variant analysis in a high-risk population enabled by whole-genome sequencing has the potential to identify novel genetic factors. Although such findings may be population specific, rare functional mutations relating to PEDF and HIF regulation align with past reports and suggest a biological mechanism for suicide risk and a potential therapeutic target for intervention.

Project description:ObjectiveSuicide deaths and suicidal thoughts and behaviors are considered a public health emergency, yet their underpinnings in the brain remain elusive. The authors examined the classification accuracy of individual, environmental, and clinical characteristics, as well as multimodal brain imaging correlates, of suicidal thoughts and behaviors in a U.S. population-based sample of school-age children.MethodsChildren ages 9-10 years (N=7,994) from a population-based sample from the Adolescent Brain Cognitive Development study were assessed for lifetime suicidal thoughts and behaviors. After quality control procedures, structural MRI (N=6,238), resting-state functional MRI (N=4,134), and task-based functional MRI (range, N=4,075-4,608) were examined. Differences with Welch's t test and equivalence tests, with observed effect sizes (Cohen's d) and their 90% confidence intervals <|0.15|, were examined. Classification accuracy was examined with area under precision-recall curves (AUPRCs).ResultsAmong the 7,994 unrelated children (females, N=3,757, 47.0%), those with lifetime suicidal thoughts and behaviors based on child (N=684, 8.6%), caregiver (N=654, 8.2%), and concordant (N=198, 2.5%) reports had higher levels of social adversity and psychopathology, among themselves and their caregivers, compared with never-suicidal children (N=6,854, 85.7%). Only one imaging test survived statistical correction: caregiver-reported suicidal thoughts and behaviors were associated with a thinner left bank of the superior temporal sulcus. On the basis of the prespecified bounds of |0.15|, approximately 48% of the group mean differences for child-reported suicidal thoughts and behaviors comparisons and approximately 22% for caregiver-reported suicidal thoughts and behaviors comparisons were considered equivalent. All observed effect sizes were relatively small (d≤|0.30|), and both non-imaging and imaging correlates had low classification accuracy (AUPRC ≤0.10).ConclusionsCommonly applied neuroimaging measures did not reveal a discrete brain signature related to suicidal thoughts and behaviors in youths. Improved approaches to the neurobiology of suicide are critically needed.

Dataset Information

Polygenic Contributions to Suicidal Thoughts and Behaviors in a Sample Ascertained for Alcohol Use Disorders.

Introduction

Methods

Results

Conclusion

Publications

Polygenic Contributions to Suicidal Thoughts and Behaviors in a Sample Ascertained for Alcohol Use Disorders.

Similar Datasets

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