Grace Chan

Background: The widespread prevalence of alcohol use disorder (AUD) and availability of treatments contrasts with limited treatment utilization. Here, in the Collaborative Studies on the Genetics of Alcoholism (COGA), we examined the extent to which genetic factors (i.e., family‐based heritability ( h ² _GCTA ), polygenic scores [PGS]) are associated with individual differences in AUD treatment utilization that could be leveraged to target intervention efforts. Methods: Non‐proband COGA participants with a lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM‐5) AUD diagnosis, whose genomic ancestry resembled that of European (EUR‐like: N = 3148; 370 nuclear families; 222 extended family pedigrees) and African (AFR‐like: N = 962; 92 nuclear families; 79 extended family pedigrees) reference panels were selected for analyses. AUD treatment h ² _GCTA and associations with PGS (i.e., alcohol involvement, cigarette use, psychopathology, externalizing behavior, and cognition‐related) were estimated, along with between‐ and within‐family effects of the PGSs. Results: AUD treatment was heritable ( h ² _GCTA = 0.36; SE = 0.06) and positively associated with PGS for problematic alcohol use, drinks/week, externalizing behavior, depression, anxiety and schizophrenia/bipolar (ORs > 1.12) while being negatively associated with education attainment (OR = 0.90) in the EUR‐like sample after accounting for AUD severity ( p _FDR ≤ 0.04). When all significant PGSs were simultaneously included, only alcohol PGSs remained significant. There were no significant PGS associations in within‐family analyses. Despite a nominally significant positive association with cigarettes per day, no PGSs were associated with AUD treatment following FDR adjustment in the AFR‐like sample. Conclusions: Genetic factors underlying alcohol use influence AUD treatment utilization, but this phenotype is largely not significantly associated with current estimates of polygenic scores for other complex traits; this suggests a potential unique genetic etiology requiring further investigation with a genome‐wide association study. The lack of significant within‐family PGS associations may have likely arisen from power reductions due to restricting the sample to full siblings. Together, these findings highlight potential facets influencing the underutilization of AUD treatment.

Background. Alcohol use disorder (AUD) and cannabis use disorder (CUD) are often comorbid. Concurrent or simultaneous use of alcohol and cannabis is associated with poorer mental health outcomes in cross-sectional studies. Here, we examined whether lifetime history of comorbid AUD and CUD is associated with emotional well-being, above and beyond current substance use and lifetime major depression. Methods. Participants were 1,393 adults from the Collaborative Study on the Genetics of Alcohol Lifespan assessment (Mage= 52.0, 59.7% female). Emotional well-being was assessed across six domains from the NIH Toolbox Emotion Battery: loneliness, perceived stress, negative affect, social satisfaction, psychological well-being, and self-efficacy. Associations between lifetime diagnostic group (comorbid AUD + CUD, AUD without CUD, CUD without AUD, or neither disorder) and emotional well-being outcomes were assessed using multivariate linear regression. Covariates included age, sex, and past-year nicotine, cannabis, and alcohol use. Sensitivity analyses adjusted for lifetime major depressive disorder.Results. Individuals with comorbid lifetime AUD + CUD reported higher loneliness, perceived stress, and negative affect, and lower social satisfaction, psychological well-being, and self-efficacy compared to other groups. Individuals with lifetime AUD without CUD or CUD without AUD generally resembled those with neither disorder across several emotional well-being domains, though those in the AUD without CUD group reported greater negative affect and lower social satisfaction and psychological well-being than the group with neither disorder. Conclusions. A lifetime history of comorbid AUD and CUD is associated with diminished emotional well-being, underscoring the need for additional psychosocial supports to address these challenges in this population.

Background: Marital transitions and stability are key social determinants of alcohol use, yet their impact across different life stages remains underexplored. This study utilizes a lifespan‐oriented approach to examine longitudinal associations between marital status and alcohol consumption and problems and to investigate underlying sex differences. Methods: Longitudinal data from two components (early mid‐life and later‐life) of the Collaborative Study on the Genetics of Alcoholism (COGA) were included, with participants averaging 33 (early mid‐life) and 62 (later‐life) years of age at their last interview. Participants were categorized into distinct groups based on their marital history across assessment waves: persistently married (reference), never married, divorced/separated, widowed, and three transition groups (into marriage, out of marriage, and mixed transitions). Alcohol use measures included past 12‐month alcohol symptom counts, past 6‐month typical drinks per week, and past 6‐month maximum drinks consumed in 24 h. Generalized linear mixed models estimated cohort‐specific risks. Results: Across both cohorts, alcohol consumption declined with age, while AUD symptom counts significantly increased ( p < 0.001). In the later‐life sample, never married individuals exhibited the highest likelihood of AUD symptoms (IRR = 3.82, p < 0.001). A significant sex interaction indicated widowhood was associated with a threefold increase in AUD symptoms (IRR = 3.46, p = 0.003), whereas widowhood was relatively protective among women (reference group). In the early mid‐life sample, transitioning out of marriage emerged as a primary correlate of symptom escalation (IRR = 2.13, p < 0.001). Conclusion: Marital stability buffers against AUD problems across the lifespan. However, the risks associated with marital instability are highly specific: marital exit poses a critical threat in early mid‐life, while widowhood represents a profound vulnerability for older men. Interventions should be tailored with attention to life stage and sex‐specific risks to mitigate alcohol‐related harm during marital transitions.

Background: Research suggests that multiple genetically influenced pathways of risk impact alcohol use disorder (AUD), including externalizing (disinhibition, behavioral undercontrol), internalizing (negative affect, depression), and alcohol‐specific (physiological response to alcohol) factors. This study examined the joint effects of genetic influences representing these risk domains on AUD and their influence on comorbid phenotypes among individuals with AUD. Methods: Participants of European‐like ancestry from the Collaborative Study on the Genetics of Alcoholism ( N = 6883) provided data on lifetime AUD, conduct disorder (CD), antisocial personality disorder (ASPD), major depressive disorder (MDD), alcohol expectancies, sensation seeking, and neuroticism. Polygenic scores (PGS) representing externalizing (EXT), major depressive disorder (MDD), and alcohol‐specific (ALC‐sp) risk were calculated. First, participants were grouped based on combinations of high versus low (top vs. bottom 30%) EXT, MDD, and ALC‐sp PGS ( n = 2006), and AUD outcomes were compared across groups. Second, among individuals with AUD, psychopathology, alcohol expectancies, sensation seeking, and neuroticism were compared across those with high versus low EXT ( n = 1664), MDD ( n = 1620), and ALC‐sp ( n = 1669) PGS. Results: Participants with three high PGS and those with high EXT + high ALC‐sp PGS had the most severe AUD outcomes. High EXT + high MDD PGS and high MDD + high ALC‐sp PGS groups generally did not differ from groups with only one high PGS. Comparisons between groups with only one high PGS were not significant. Among individuals with AUD, high EXT PGS was associated with CD/ASPD, arousal/aggression alcohol expectancies, and relaxation/tension reduction alcohol expectancies; high MDD PGS was associated with MDD and neuroticism. Conclusions: Quantity and type of genetic risk are important for AUD outcomes. EXT plays an outsized role in AUD, particularly in the presence of other high PGS, and may potentiate alcohol expectancies that reinforce harmful patterns of use. Findings elucidate the role of multiple pathways of genetic risk for AUD and how they impact comorbid phenotypes.

Objectives: The retrospective self‐report of the effects of alcohol (SRE) questionnaire generates three scores reflecting drinking quantities required for effects: SRE‐5 (first five times of drinking), SRE‐3 (recent 3 months of drinking), and SRE‐H (heaviest drinking). Data to date indicate that SRE‐5 scores, potentially reflecting genetic effects, have high reliabilities across 9 months. Data presented here evaluated the consistencies of all three SRE scores obtained five times over a decade. Method: Participants were 331 young adults (45% male) from the Collaborative Study on the Genetics of Alcoholism (COGA) Prospective Study of youth who completed the SRE and were evaluated at least five times using the Semi‐Structured Assessment for the Genetics of Alcoholism interview. Analyses documented changes in SRE scores, changes in drinking quantities, and the relationship between these measures over time using repeated measures ANOVA and regression analyses. Results: SRE‐5 scores did not change significantly across evaluations despite significant changes in drinking quantities. SRE‐3 and SRE‐H demonstrated significant changes over time that related to changes in drinking quantities during each period. Participants with low levels of response (low LRs) to alcohol, based on a median split of SRE‐5 at Time 1, were likely to remain low LR throughout the decade. Conclusions: This is the first report on the longer‐term consistency of all three SRE scores during a decade of life in which a person's heaviest drinking and AUD development are likely to occur. Results indicate that retrospective SRE‐5 scores, potentially reflecting genetic predispositions to AUD, do not change over a decade despite changes in drinking patterns.

Background: Romantic relationships are important contexts for substance use and emotional well-being. We tested the hypotheses that (i) genetic predispositions for alcohol consumption would be positively associated with partner substance use, (ii) partner substance use would moderate genetic influences on one’s own alcohol outcomes, and (iii) partner discordance in substance use would be associated with lower emotional well-being and relationship quality. Methods: Analyses included 2,357 participants (M _age = 51.4, 58.2% female) from the Collaborative Studies on the Genetics of Alcoholism. Focal measures included participants’ reports of their own and their current partner’s past-year substance use (frequencies of alcohol use, heavy drinking, drunkenness, cannabis use, and nicotine use), emotional well-being, and relationship quality. Participants’ genetic predispositions were indexed with genome-wide polygenic scores for alcohol consumption (PGS _Alc ). Participant–partner substance use discordance was calculated as the difference between the participant’s and their partner’s use for each substance use measure, separately. Results: Participant PGS _Alc was not significantly associated with partners’ perceived substance use. Frequent perceived partner alcohol use and heavy drinking significantly amplified the association between PGS _Alc and alcohol use or drunkenness. Frequent perceived partner drunkenness and cannabis use significantly attenuated the association between PGS _Alc and heavy drinking or frequency of alcohol use. Participant–partner discordance for several substance use measures was significantly associated with lower emotional well-being and relationship quality, controlling for participant and partner substance use main effects. Conclusions: The results highlight the importance of partner substance use in etiological models of alcohol use, emotional health outcomes, and relationship quality.

Background Social-Emotional Health (SEH)—the quality of social relationships and emotional well-being—is crucial for maintaining health and cognitive functioning. Given elevated cognitive impairment risk in aging and Alcohol Use Disorder (AUD) populations, we investigated associations between specific SEH factors and cognitive and physical functioning in individuals from families enriched for AUD. Methods Data from the Collaborative Study on the Genetics of Alcoholism (COGA, analytic N = 1,476, 61% lifetime AUD) were analyzed, grouping participants into younger (22–49 years) and later-life (50 + years) adults. Six SEH factors, fluid cognition (e.g., logical reasoning), and crystallized cognition (e.g., vocabulary) were measured via the NIH Toolbox Cognition and Emotion batteries. Physical functioning (SF-36), a self-reported measure of general health, was included as a non-cognitive comparison, with age and gender tested as moderators. Results SEH associations with fluid cognition and physical functioning were robust and conditional on age and gender. In later-life adults, all three positive SEH factors (Emotional Support, Instrumental Support, Friendship) were associated with higher fluid cognition, while all three negative factors (Loneliness, Negative Affect, Perceived Stress) were associated with lower fluid cognition. These associations were predominantly observed in later-life women and were independent of lifetime AUD history. While physical functioning showed widespread SEH associations across groups, SEH was not associated with fluid cognition in younger adults. Conclusion SEH shows robust, age- and gender-specific associations with fluid cognition and physical health. The SEH-fluid cognition link appears to be a late-life phenomenon particularly salient for women and independent of an individual’s lifetime AUD history.

Objective: Marriage is associated with improved health and alcohol outcomes, yet prior research has often combined diverse non-marital relationships, obscuring whether benefits are unique to marriage or a result of strong interpersonal relationships. This study examines whether marriage, compared to cohabitation, exclusive dating, or being single, is associated with alcohol use disorder (AUD) remission and whether this varies by sex and partner drinking. Method: Participants were adults from the Collaborative Study on the Genetics of Alcoholism Lifespan Study (n = 1494; 54.4% female) who met criteria for lifetime DSM-5 AUD. Multivariate logistic regression models examined the association between marital status and remission. Subsequent models tested interactions among marital status, partner drinking, and sex. Predicted remission prevalence was estimated using marginal standardization and compared across groups on an additive scale using prevalence differences (PD). Results: Married individuals had greater predicted prevalence of remission, particularly compared to those who were exclusively dating (PD = 9.2, P = .020). Married females whose partners were average alcohol consumers (PD = 12.20, q = .049) or abstinent (PD = 17.98, q = .017), and married males whose partners had above average alcohol consumption (PD = 25.30, q = .049) had greater predicted prevalence of remission compared to their counterparts who were in non-marital committed relationships. Conclusion: The findings suggest differences in marital status and relationship factors may indicate increased risk and challenges in sustaining remission and highlight potential caveats of marital status as a protective factor. This emphasizes the need to consider these factors in designing treatment strategies.