ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2022
Genetic overlap between mood instability and alcohol-related phenotypes suggests shared biological underpinnings.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Subjective response to alcohol: Interactive effects of early life stress, parental risk for mood and substance use disorders, and drinking context.Pharmacology, biochemistry, and behavior · 2023Trial
- Major depressive disorder-alcohol use disorder comorbidity: diagnosis, mechanisms and treatment.European archives of psychiatry and clinical neuroscience · 2026Review
- Shared Genetic Networks in Schizophrenia and Bipolar Disorder: Hippocampal Volume-Mediated Neurobiological Mechanisms.Schizophrenia bulletin · 2026Article
- The influence of CHRNA5 and D398N missense variation on social and emotional behaviors in rodents and humans.Translational psychiatry · 2025Article
- The effects of polygenic risks for alcohol misuse on negative emotion processing in young adult binge drinkers.Translational psychiatry · 2025Article
- Distinct patterns of genetic overlap among multimorbidities revealed with trivariate MiXeR.Genome medicine · 2025Article
- Co-Occurring Bipolar and Substance Use Disorders: A Review of Impacts, Biopsychosocial Mechanisms, Assessment, and Treatment.Focus (American Psychiatric Publishing) · 2025Review
- Polygenic overlap of substance use behaviors and disorders with externalizing and internalizing problems independent of genetic correlations.Psychological medicine · 2025Article
- Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens in male rats.Nature communications · 2025Article
- Effects of core self-evaluation on tobacco and alcohol use among left-behind children: mediating role of fear of missing out and moderating role of parental migration category and gender.BMC psychology · 2025Article
- Identification of risk variants and cross-disorder pleiotropy through multi-ancestry genome-wide analysis of alcohol use disorder.Nature. Mental health · 2025Article
- Mood instability and risk of gastrointestinal diseases - a univariable and multivariable mendelian randomization study.Annals of general psychiatry · 2024Article
- Genome-wide analyses reveal shared genetic architecture and novel risk loci between opioid use disorder and general cognitive ability.Drug and alcohol dependence · 2024Article
- Dissecting the genetic overlap between three complex phenotypes with trivariate MiXeR.medRxiv : the preprint server for health sciences · 2024Article
- Bidirectional genetic overlap between bipolar disorder and intelligence.BMC medicine · 2022Article
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17 authors.
Funding
Abstract
Alcohol use disorder (AUD) is a pervasive and devastating mental illness with high comorbidity rates with other mental disorders. Understanding the genetic architecture of this comorbidity could be improved by focusing on intermediate traits that show positive genetic correlation with the disorders. Thus, we aimed to characterize the shared vs. unique polygenicity of AUD, alcohol consumption (AC) and mood instability (MOOD) -beyond genetic correlation, and boost discovery for jointly-associated loci. Summary statistics for MOOD (a binary measure of the tendency to report frequent mood swings), AC (number of standard drinks over a typical consumption week) and AUD GWASs (Ns > 200,000) were analyzed to characterize the cross-phenotype associations between MOOD and AC, MOOD and AUD and AC and AUD. To do so, we used a newly established pipeline that combines (i) the bivariate causal mixture model (MiXeR) to quantify polygenic overlap and (ii) the conjunctional false discovery rate (conjFDR) to discover specific jointly associated genomic loci, which were mapped to genes and biological functions. MOOD was highly polygenic (10.4k single nucleotide polymorphisms, SNPs, SD = 2k) compared to AC (4.9k SNPs, SD = 0.6k) and AUD (4.3k SNPs, SD = 2k). The polygenic overlap of MOOD and AC was twice that of MOOD and AUD (98% vs. 49%), with opposite genetic correlation (-0.2 vs. 0.23), as confirmed in independent samples. MOOD&AUD associated SNPs were significantly enriched for brain genes, conversely to MOOD&AC. Among 38 jointly associated loci, fifteen were novel for MOOD, AC and AUD. MOOD, AC and AUD were also strongly associated at the phenotypic level. Overall, using multilevel polygenic quantification, joint loci discovery and functional annotation methods, we evidenced that the polygenic overlap between MOOD and AC/AUD implicated partly shared biological underpinnings, yet, clearly distinct functional patterns between MOOD&AC and MOOD&AUD, suggesting new mechanisms for the comorbidity of AUD with mood disorders.
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