Clinical, genomic, and neurophysiological correlates of lifetime suicide attempts among individuals with alcohol dependence.
paper
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Public
Preprint
- Authors
- Barr, Peter; Neale, Zoe; Chatzinakos, Chris; Schulman, Jessica; Mullins, Niamh; Zhang, Jian; Chorlian, David; Kamarajan, Chella; Kinreich, Sivan; Pandey, Ashwini; Pandey, Gayathri; de Viteri, Stacey Saenz; Acion, Laura; Bauer, Lance; Bucholz, Kathleen; Chan, Grace; Dick, Danielle; Edenberg, Howard; Foroud, Tatiana; Goate, Alison; Hesselbrock, Victor; Johnson, Emma; Kramer, John; Lai, Dongbing; Plawecki, Martin; Salvatore, Jessica; Wetherill, Leah; Agrawal, Arpana; Porjesz, Bernice; Meyers, Jacquelyn
- Year
- 2024
- Journal
- Research square
- PMID
- 38405959
- DOI
- 10.21203/rs.3.rs-3894892/v1
- PMCID
- PMC10889049
- Published as
- Clinical, Genomic, and Neurophysiological Correlates of Lifetime Suicide Attempts among Individuals with an Alcohol Use Disorder. →
Research has identified clinical, genomic, and neurophysiological markers associated with suicide attempts (SA) among individuals with psychiatric illness. However, there is limited research among those with an alcohol use disorder (AUD), despite their disproportionately higher rates of SA. We examined lifetime SA in 4,068 individuals with DSM-IV alcohol dependence from the Collaborative Study on the Genetics of Alcoholism (23% lifetime suicide attempt; 53% female; 17% Admixed African American ancestries; mean age: 38). We 1) conducted a genome-wide association study (GWAS) of SA and performed downstream analyses to determine whether we could identify specific biological pathways of risk, and 2) explored risk in aggregate across other clinical conditions, polygenic scores (PGS) for comorbid psychiatric problems, and neurocognitive functioning between those with AD who have and have not reported a lifetime suicide attempt. The GWAS and downstream analyses did not produce any significant associations. Participants with an AUD who had attempted suicide had greater rates of trauma exposure, major depressive disorder, post-traumatic stress disorder, and other substance use disorders compared to those who had not attempted suicide. Polygenic scores for suicide attempt, depression, and PTSD were associated with reporting a suicide attempt (ORs = 1.22-1.44). Participants who reported a SA also had decreased right hemispheric frontal-parietal theta and decreased interhemispheric temporal-parietal alpha electroencephalogram resting-state coherences relative to those who did not, but differences were small. Overall, individuals with alcohol dependence who report SA appear to experience a variety of severe comorbidities and elevated polygenic risk for SA. Our results demonstrate the need to further investigate suicide attempts in the presence of substance use disorders.
Polygenic Scores for AUD, DEP and SUI across those who have and have not reported a suicide attemptPanel A presents odds ratios (OR) for AUD, DEP, and SUI PGSs from logistic regression models in persons with AD who had and had not attempted suicide. Panel B presents OR from multinomial logistic models (no AD, no suicide attempt as reference group). All models include cohort, sex, PC1-PC3, array, and site as covariates. SEs adjusted for familial clustering using cluster-robust standard errors. AFR = African Ancestries, EUR = European Ancestries, AUD = alcohol use disorder polygenic score, DEP = depression polygenic score, = SUI suicide attempt polygenic score, SA− = no lifetime suicide attempt, AD− = does not meet criteria for alcohol dependence, SA+ = lifetime suicide attempt, AD+ = meets criteria for alcohol dependence.
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| Name | Type |
|---|---|
| 1000G African panel local | cohort |
| 1000 Genomes Phase 3 local | drug |
| 1000G European ancestries reference panel local | cohort |
| 1000G European panel local | cohort |
| 23andMe | cohort |
| ADH1B | gene |
| ADH1C | gene |
| ADH4 | gene |
| Admixed African American ancestry (AFR) local | cohort |
| AD+ SA+ group local | cohort |
| AD+ SA- group local | cohort |
| AD- SA+ group local | cohort |
| AD- SA- group local | cohort |
| Affymetrix Smokescreen array local | drug |
| AFR | cohort |
| African American | cohort |
| African ancestry participants local | cohort |
| AFR sample local | cohort |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| alcohol-related problems | phenotype |
| Alcohol Use Disorder | phenotype |
| Alcohol Use Disorders Identification Test | phenotype |
| Alpha coherence | phenotype |
| Alzheimer's disease | phenotype |
| American Indian adolescents local | cohort |
| ARNTL2 local | gene |
| AUD | phenotype |
| AUD-adjacent phenotypes local | phenotype |
| AUD PGS local | drug |
| AUD polygenic score local | phenotype |
| AUD treatment seekers local | cohort |
| Beta coherence local | phenotype |
| binge drinking | phenotype |
| bipolar disorder | phenotype |
| BIP PGS local | drug |
| birth cohort | cohort |
| brain | anatomy |
| chr4_23273116_D local | variant |
| cocaine use disorder | phenotype |
| COGA sample | cohort |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| Decreased alpha coherence local | phenotype |
| Decreased theta coherence local | phenotype |
| DEP PGS local | drug |
| DEP polygenic score local | phenotype |
| depressed patients | cohort |
| depression | phenotype |
| Depression PGS local | drug |
| DRD2 | gene |
| drug dependence | phenotype |
| Drug-related suicide attempt local | phenotype |
| Early Drinking Age local | phenotype |
| EEG coherence | phenotype |
| Ensembl v92 local | drug |
| EUR | cohort |
| European ancestry | cohort |
| European ancestry (EUR) local | cohort |
| European population | cohort |
| executive functioning | phenotype |
| FAH local | gene |
| family history of alcoholism | phenotype |
| FinnGen | cohort |
| frontal cortex | anatomy |
| Frontal-parietal cortex local | anatomy |
| FTO | gene |
| FUMA | drug |
| functional connectivity | phenotype |
| GCKR | gene |
| general population | cohort |
| genes | gene |
| GTEx v8 | cohort |
| GWAS | cohort |
| Higher beta coherence local | phenotype |
| Illumina 2.5M array | drug |
| Illumina Human1M array | drug |
| Illumina OmniExpress | drug |
| Interhemispheric temporal-parietal alpha coherence local | anatomy |
| JCAD | gene |
| Klb | gene |
| LDHB | gene |
| lower neurophysiological functioning local | phenotype |
| MAGMA | drug |
| major depressive disorder | phenotype |
| Mexican American adolescents local | cohort |
| Million Veteran Program | cohort |
| mood disorders | phenotype |
| Neurophysiological Profiles local | phenotype |
| neuropsychological deficits | phenotype |
| nicotine | drug |
| nicotine dependence | phenotype |
| opioid dependence | phenotype |
| other psychiatric disorders | phenotype |
| other substances | phenotype |
| parietal cortex | anatomy |
| PGs | drug |
| physical abuse | phenotype |
| polygenic risk score | cohort |
| polygenic score for depression local | phenotype |
| polygenic score for PTSD local | phenotype |
| polygenic score for suicide attempt local | phenotype |
| Post-Traumatic Stress Disorder | phenotype |
| problematic alcohol use | phenotype |
| psychiatric disorders | phenotype |
| Psychiatric Genomics Consortium | cohort |
| PTSD PGS local | drug |
| Right hemispheric frontal-parietal theta coherence local | anatomy |
| rs11876255 local | variant |
| rs138689899 local | variant |
| rs1677091 local | variant |
| rs45593736 local | variant |
| rs683813 local | variant |
| rs72740082 local | variant |
| rs7906104 local | variant |
| SA | phenotype |
| schizophrenia | phenotype |
| SCZ PGS local | drug |
| sexual trauma | phenotype |
| SIX3 | gene |
| SLC39A13 | gene |
| SLC39A8 | gene |
| smoking initiation | phenotype |
| SMOK PGS local | drug |
| SMOK polygenic score local | phenotype |
| SNP | cohort |
| substance use | phenotype |
| suicide | phenotype |
| Suicide attempt PGS local | drug |
| SUI PGS local | drug |
| SUI polygenic score local | phenotype |
| temporal cortex | anatomy |
| Temporal-parietal cortex local | anatomy |
| temporal region | anatomy |
| Theta coherence | phenotype |
| trait | phenotype |
| trauma exposure | phenotype |
| UK Biobank | cohort |
| United States | cohort |
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