BACKGROUND:The field's conventional understanding of how genetic factors impact risk for alcohol use disorder (AUD) typically focuses on direct genetic effects, or how an individual's own genetic predispositions are associated with the likelihood of experiencing clinically significant alcohol problems. More recently, studies of behavioral health outcomes in preclinical and human studies have demonstrated the potential importance of social genetic effects or the influence of a social partner's genotype on substance use and related outcomes. In this study, we sought to characterize social genetic effects for AUD, specifically in the context of marriage. METHODS:The sample included 660 opposite-sex spousal dyads from the Collaborative Study on the Genetics of Alcoholism, restricted to individuals who were genetically similar to European reference panels. Measured and latent indicators of genetic risk included polygenic scores of problematic alcohol use (PGSPAU) and parental history of AUD (PHAUD), respectively. The outcome was Diaganostic and Statistical Manual (DSM)-5 alcohol use disorder criterion count (AUDcrit) during marriage. Multilevel models accounted for the non-independence of partners' data, including correlations between partners' genetic risk and residual covariance in AUDcrit. RESULTS:After accounting for direct genetic effects (i.e., the influence of one's own genetic predispositions) and the correlations between partners' genetic predispositions, we found that having a spouse with higher PGSPAU was associated with higher AUDcrit (B = 0.084, 95% CI [0.035, 0.132]). This social genetic effect was robust after adjusting for both partners' educational attainment. Spousal PHAUD was not associated with AUDcrit. Exploratory analyses indicated that the social genetic effect of spousal PGSPAU was stronger among male target individuals. CONCLUSIONS:Findings highlight the potential importance of social genetic effects for understanding the pathways from genotype to alcohol use disorder and the need for further investigation of latent measures of genetic predispositions in studies of social genetic effects.

Introduction:Research has identified multiple risk factors associated with suicide attempt (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. Methods:We examined lifetime SA in 4,068 individuals with an AUD from the Collaborative Study on the Genetics of Alcoholism (23% lifetime SA; 53% female; mean age: 38). We explored risk for lifetime SA across other clinical conditions ascertained from a clinical interview, polygenic scores for comorbid psychiatric problems, and neurocognitive functioning. Results:Participants with an AUD who attempted suicide had greater rates of trauma exposure, major depressive disorder, post-traumatic stress disorder, other substance use disorders (SUDs), and suicidal ideation. Polygenic scores for SA, depression, and PTSD were associated with increased odds of reporting an SA (ORs = 1.22-1.44). Participants who reported an 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. Conclusions:Overall, individuals with an AUD who report lifetime SA experience greater levels of trauma, have more severe comorbidities, and carry increased polygenic risk for other psychiatric problems. Our results demonstrate the need to further investigate SAs in the presence of SUDs.

Objective Parental separation and relationship discord are linked to alcohol use behaviors, but their influence on the longitudinal course of alcohol misuse and interactions with genetic predisposition remain unclear. This study examined how the longitudinal course of heavy episodic drinking (HED) from adolescence to young adulthood varies with polygenic risk, parental separation, and relationship discord. Method Participants were from the Collaborative Study on the Genetics of Alcoholism (COGA) Prospective Sample, and included individuals from 2 genetically inferred continental groups: European-like (EA; n = 1761) and African-like (AA; n = 894) who were reassessed biennially (mean age = 16.39 at first assessment; mean assessments = 4.65). Alcohol misuse was indexed by past-year HED frequency. Predictors included parental separation, parental relationship discord, and problematic alcohol use polygenic scores (PGSPAU). Data were analyzed using linear mixed-effects growth models. Results HED increased through young adulthood before declining. In European Americans (EA), parental separation was associated with HED intercepts, but not with linear slope or quadratic curvature. Higher PGSPAU was associated with a faster initial growth and slower decline. In African American (AA), parental relationship discord was not associated with HED intercepts but was associated with a faster initial growth and slower decline. PGSPAU were not associated the intercept or the course of HED. No interaction was found between PGSPAU and parental separation or discord to predict the longitudinal course of HED in either EA or AA samples. Conclusion Genetic risk and exposure to parental separation and discord are associated with the course of HED, with some differences across continental groups. Plain language summary This study utilized data from the Collaborative Study on the Genetics of Alcoholism (COGA) to examine how the course of heavy episodic drinking (HED) from adolescence to young adulthood varies with genetic risk, parental separation, and relationship discord. Parental separation and relationship discord were associated with initial levels of heavy episodic drinking and their course into young adulthood. In the European American sample, these family stressors were associated with higher initial levels of heavy episodic drinking, which were sustained over time with genetic factors amplifying this pattern. In the African American sample, parental relationship discord was associated with a rapid increase in heavy episodic drinking that declined slowly. These findings highlight the contributions of genetics and family adversity in shaping risk for harmful patterns of alcohol use across development.

BACKGROUND:Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk. METHODS:Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11-36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones. RESULTS:Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20). CONCLUSIONS:Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Some sources report increases in alcohol use have been observed since the start of the COVID-19 pandemic, particularly among women. Cross-sectional studies suggest that specific COVID-19-related stressful experiences (e.g., social disconnection) may be driving such increases in the general population. Few studies have explored these topics among individuals with a history of Alcohol Use Disorders (AUD), an especially vulnerable population. Drawing on recent data collected by the Collaborative Study on the Genetics of Alcoholism (COGA; COVID-19 study N = 1651, 62% women, age range: 30–91) in conjunction with AUD history data collected on the sample since 1990, we investigated associations of COVID-19 related stressors and coping activities with changes in drunkenness frequency since the start of the pandemic. Analyses were conducted for those without a history of AUD ( N : 645) and three groups of participants with a history of AUD prior to the start of the pandemic: (1) those experiencing AUD symptoms ( N : 606), (2) those in remission who were drinking ( N : 231), and (3) those in remission who were abstinent (had not consumed alcohol for 5+ years; N : 169). Gender-stratified models were also examined. Exploratory analyses examined the moderating effects of ‘problematic alcohol use’ polygenic risk scores (PRS) and neural connectivity (i.e., posterior interhemispheric alpha EEG coherence) on associations between COVID-19 stressors and coping activities with changes in the frequency of drunkenness. Increases in drunkenness frequency since the start of the pandemic were higher among those with a lifetime AUD diagnosis experiencing symptoms prior to the start of the pandemic (14% reported increased drunkenness) when compared to those without a history of AUD (5% reported increased drunkenness). Among individuals in remission from AUD prior to the start of the pandemic, rates of increased drunkenness were 10% for those who were drinking pre-pandemic and 4% for those who had previously been abstinent. Across all groups, women reported nominally greater increases in drunkenness frequency when compared with men, although only women experiencing pre-pandemic AUD symptoms reported significantly greater rates of increased drunkenness since the start of the pandemic compared to men in this group (17% of women vs. 5% of men). Among those without a prior history of AUD, associations between COVID-19 risk and protective factors with increases in drunkenness frequency were not observed. Among all groups with a history of AUD (including those with AUD symptoms and those remitted from AUD), perceived stress was associated with increases in drunkenness. Among the remitted-abstinent group, essential worker status was associated with increases in drunkenness. Gender differences in these associations were observed: among women in the remitted-abstinent group, essential worker status, perceived stress, media consumption , and decreased social interactions were associated with increases in drunkenness. Among men in the remitted-drinking group, perceived stress was associated with increases in drunkenness, and increased relationship quality was associated with decreases in drunkenness. Exploratory analyses indicated that associations between family illness or death with increases in drunkenness and increased relationship quality with decreases in drunkenness were more pronounced among the remitted-drinking participants with higher PRS. Associations between family illness or death, media consumption , and economic hardships with increases in drunkenness and healthy coping with decreases in drunkenness were more pronounced among the remitted-abstinent group with lower interhemispheric alpha EEG connectivity. Our results demonstrated that only individuals with pre-pandemic AUD symptoms reported greater increases in drunkenness frequency since the start of the COVID-19 pandemic compared to those without a lifetime history of AUD. This increase was more pronounced among women than men in this group. However, COVID-19-related stressors and coping activities were associated with changes in the frequency of drunkenness among all groups of participants with a prior history of AUD, including those experiencing AUD symptoms, as well as abstinent and non-abstinent participants in remission. Perceived stress, essential worker status, media consumption , social connections (especially for women), and relationship quality (especially for men) are specific areas of focus for designing intervention and prevention strategies aimed at reducing pandemic-related alcohol misuse among this particularly vulnerable group. Interestingly, these associations were not observed for individuals without a prior history of AUD, supporting prior literature that demonstrates that widespread stressors (e.g., pandemics, terrorist attacks) disproportionately impact the mental health and alcohol use of those with a prior history of problems.

Recent genome-wide association studies (GWAS) have identified genetic markers of post-traumatic stress disorder (PTSD) in civilian and military populations. However, studies have yet to examine the genetics of PTSD while factoring in risk for alcohol dependence, which commonly co-occur. We examined genome-wide associations for DSM-IV PTSD among 4,978 trauma-exposed participants (31% with alcohol dependence, 50% female, 30% African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA). We also examined associations of polygenic risk scores (PRS) derived from the Psychiatric Genomics Consortium (PGC)-PTSD Freeze 2 ( N = 3533) and Million Veterans Program GWAS of PTSD ( N = 5200) with PTSD and substance dependence in COGA, and moderating effects of sex and alcohol dependence. 7.3% of COGA participants met criteria for PTSD, with higher rates in females (10.1%) and those with alcohol dependence (12.3%). No independent loci met genome-wide significance in the PTSD meta-analysis of European (EA) and African ancestry (AA) participants. The PGC-PTSD PRS was associated with increased risk for PTSD ( B = 0.126, p < 0.001), alcohol dependence ( B = 0.231, p < 0.001), and cocaine dependence ( B = 0.086, p < 0.01) in EA individuals. A significant interaction was observed, such that EA individuals with alcohol dependence and higher polygenic risk for PTSD were more likely to have PTSD ( B = 0.090, p < 0.01) than those without alcohol dependence. These results further support the importance of examining substance dependence, specifically alcohol dependence, and PTSD together when investigating genetic influence on these disorders.

BACKGROUND:Parental divorce and discord are associated with poorer alcohol-related outcomes for offspring. However, not all children exposed to these stressors develop alcohol problems. Our objective was to test gene-by-environment interaction effects whereby children's genetic risk for alcohol problems modifies the effects of parental divorce and discord to predict alcohol outcomes. METHODS:The sample included European (EA; N = 5608, 47% male, Mage  ~ 36 years) and African (AA; N = 1714, 46% female, Mage  ~ 33 years) ancestry participants from the Collaborative Study on the Genetics of Alcoholism. Outcomes included age at initiation of regular drinking and lifetime DSM-5 alcohol use disorder (AUD). Predictors included parental divorce, parental relationship discord, and offspring alcohol problems polygenic risk scores (PRSALC ). Mixed effects Cox proportional hazard models were used to examine alcohol initiation and generalized linear mixed effects models were used to examine lifetime AUD. Tests of PRS moderation of the effects of parental divorce/relationship discord on alcohol outcomes were examined on multiplicative and additive scales. RESULTS:Among EA participants, parental divorce, parental discord, and higher PRSALC were associated with earlier alcohol initiation and greater lifetime AUD risk. Among AA participants, parental divorce was associated with earlier alcohol initiation and discord was associated with earlier initiation and AUD. PRSALC was not associated with either. Parental divorce/discord and PRSALC interacted on an additive scale in the EA sample, but no interactions were found in AA participants. CONCLUSIONS:Children's genetic risk for alcohol problems modifies the impact of parental divorce/discord, consistent with an additive model of diathesis-stress interaction, with some differences across ancestry.

This review describes the genetic approaches and results from the family-based Collaborative Study on the Genetics of Alcoholism (COGA). COGA was designed during the linkage era to identify genes affecting the risk for alcohol use disorder (AUD) and related problems, and was among the first AUD-focused studies to subsequently adopt a genome-wide association (GWAS) approach. COGA's family-based structure, multimodal assessment with gold-standard clinical and neurophysiological data, and the availability of prospective longitudinal phenotyping continues to provide insights into the etiology of AUD and related disorders. These include investigations of genetic risk and trajectories of substance use and use disorders, phenome-wide association studies of loci of interest, and investigations of pleiotropy, social genomics, genetic nurture, and within-family comparisons. COGA is one of the few AUD genetics projects that includes a substantial number of participants of African ancestry. The sharing of data and biospecimens has been a cornerstone of the COGA project, and COGA is a key contributor to large-scale GWAS consortia. COGA's wealth of publicly available genetic and extensive phenotyping data continues to provide a unique and adaptable resource for our understanding of the genetic etiology of AUD and related traits.

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.

The purpose of this study was to examine possible pathways by which genetic risk associated with externalizing is transmitted in families. We used molecular data to disentangle the genetic and environmental pathways contributing to adolescent externalizing behavior in a sample of 1,111 adolescents (50% female; 719 European and 392 African ancestry) and their parents from the Collaborative Study on the Genetics of Alcoholism. We found evidence for genetic nurture such that parental externalizing polygenic scores were associated with adolescent externalizing behavior, over and above the effect of adolescents' own externalizing polygenic scores. Mediation analysis indicated that parental externalizing psychopathology partly explained the effect of parental genotype on children's externalizing behavior. We also found evidence for evocative gene-environment correlation, whereby adolescent externalizing polygenic scores were associated with lower parent-child communication, less parent-child closeness, and lower parental knowledge, controlling for parental genotype. These effects were observed among participants of European ancestry but not African ancestry, likely due to the limited predictive power of polygenic scores across ancestral background. These results demonstrate that in addition to genetic transmission, genes influence offspring behavior through the influence of parental genotypes on their children's environmental experiences, and the role of children's genotypes in shaping parent-child relationships.

Importance: Substance use disorders (SUDs) incur serious social and personal costs. Screening techniques that identify persons at risk before problems develop can improve prevention efforts. Objective: To examine whether models that include polygenic scores (PGS) and a clinical/ environmental/risk index (CERI) are able to identify individuals as having a lifetime SUD. Design: We tested the predictive power of PGS and CERI for lifetime diagnosis of DSM-IV substance dependence using four longitudinal cohorts. Setting: The study included four samples: 1) the National Longitudinal Study of Adolescent to Adult Health (Add Health); 2) the Avon Longitudinal Study of Parents and Children (ALSPAC); 3) the Collaborative Study on the Genetics of Alcoholism (COGA); and 4) the Finnish Twin Cohort Study (FinnTwin12) for a combined sample of N = 15,134. Participants: Participants in Add Health (NEUR = 4,855; NAFR = 1,605) and COGA (NEUR = 1,878; NAFR = 870) included individuals of both European and African ancestries. Participants in ALSPAC (NEUR = 4,733) and FinnTwin12 (NEUR = 1,193) were limited to individuals of European ancestries. Exposures: A clinical/environmental risk index (CERI) composed of ten items and PGS for phenotypes with strong genetic overlap with SUDs (drinks per week, problematic alcohol use, externalizing problems, major depressive disorder, and schizophrenia). Main Outcomes: Meeting lifetime criteria for DSM-IV: 1) alcohol dependence, 2) drug dependence, and 3) any substance dependence (alcohol, other drug, or nicotine). Results: In the models containing the five PGS and CERI, the CERI was associated with all three outcomes (ORs = 1.35 - 1.64). PGS for problematic alcohol use was associated with alcohol dependence (OR = 1.14), PGS for externalizing was associated with drug dependence (OR = 1.14) and both were associated with any substance dependence (ORs = 1.11 - 1.19). Including the five PGS, CERI, and covariates explained 6% - 13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.82 - 9.13 for each SUD relative to the bottom 90%. Conclusions and Relevance: Measures of clinical, environmental, and genetic, risk demonstrate modest ability to distinguish between affected and unaffected individuals for alcohol, drug, and any substance use disorders in young adulthood. These tools will continue to advance as we identify additional risk factors that can be incorporated into clinical practice and deliver on the goal of precision medicine.

OBJECTIVE To examine associations between alcohol use disorder (AUD), its psychiatric comorbidities, and their interactions, with marital outcomes in a diverse high-risk, genetically informative sample. METHOD Participants included European ancestry (EA; n = 4,045) and African ancestry (AA; n = 1,550) individuals from the multigenerational Collaborative Study on the Genetics of Alcoholism (COGA) sample (56% female, Mage ∼ 41 years). Outcomes were lifetime marriage and divorce. Predictors included lifetime AUD, an alcohol problems polygenic score (PRS), and AUD comorbidities, including conduct or antisocial personality disorder (ASP), cannabis dependence/abuse (CAN), frequent tobacco use (TOB), and major depressive disorder (MDD). Mixed effect Cox models and generalized linear mixed effects models were fit. RESULTS Among EA participants, those with AUD and CAN were less likely to marry (hazard ratios [HRs] 0.70-0.83, ps < 0.01). Among AA participants, those with AUD and TOB were less likely to marry (HRs 0.66-0.82, ps < 0.05) and those with MDD were more likely to marry (HR = 1.34, ps < 0.01). Among EA participants, AUD, CAN, TOB, and MDD were associated with higher odds of divorce (odds ratios [ORs] 1.59-2.21, ps < 0.01). Among AA participants, no predictors were significantly associated with divorce. Significant random effects indicated genetic and environmental influences on marriage, but only environmental factors on divorce. CONCLUSIONS In a high-risk sample, AUD was associated with reduced likelihood of marriage in EA and AA individuals and increased risk of divorce in EA individuals. These associations were largely independent of comorbidities. Genetic and environmental background factors contributed to marriage, while only environmental background factors contributed to divorce. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Suicidal thoughts and behaviors (STBs) and nonsuicidal self-injury (NSSI) behaviors are moderately heritable and may reflect an underlying predisposition to depression, impulsivity, and cognitive vulnerabilities to varying degrees. Objectives: We aimed to estimate the degrees of association between genetic liability to depression, impulsivity, and cognitive performance and STBs and NSSI in a high-risk sample. Methods: We used data on 7,482 individuals of European ancestry and 3,359 individuals of African ancestry from the Collaborative Study on the Genetics of Alcoholism to examine the links between polygenic scores (PGSs) for depression, impulsivity/risk-taking, and cognitive performance with 3 self-reported indices of STBs (suicidal ideation, persistent suicidal ideation defined as ideation occurring on at least 7 consecutive days, and suicide attempt) and with NSSI. Results: The PGS for depression was significantly associated with all 4 primary self-harm measures, explaining 0.6–2.5% of the variance. The PGS for risk-taking behaviors was also associated with all 4 self-harm behaviors in baseline models, but was no longer associated after controlling for a lifetime measure of DSM-IV alcohol dependence and abuse symptom counts. Polygenic predisposition for cognitive performance was negatively associated with suicide attempts (q = 3.8e−4) but was not significantly associated with suicidal ideation nor NSSI. We did not find any significant associations in the African ancestry subset, likely due to smaller sample sizes. Conclusions: Our results encourage the study of STB as transdiagnostic outcomes that show genetic overlap with a range of risk factors.

Genetic predispositions and environmental influences both play an important role in adolescent externalizing behavior; however, they are not always independent. To elucidate gene–environment interplay, we examined the interrelationships between externalizing polygenic risk scores, parental knowledge, and peer substance use in impacting adolescent externalizing behavior across two time-points in a high-risk longitudinal sample of 1,200 adolescents (764 European and 436 African ancestry; Mage = 12.99) from the Collaborative Study on the Genetics of Alcoholism. Results from multivariate path analysis indicated that externalizing polygenic scores were directly associated with adolescent externalizing behavior but also indirectly via peer substance use, in the European ancestry sample. No significant polygenic association nor indirect effects of genetic risk were observed in the African ancestry group, likely due to more limited power. Our findings underscore the importance of gene–environment interplay and suggest peer substance use may be a mechanism through which genetic risk influences adolescent externalizing behavior.

Background: Aggression often occurs alongside alcohol and drug misuse. However, it is not clear whether the latent and manifest relations among alcohol-related, drug-related, and non-substancerelated aggression are separate manifestations of a single construct or instead are three distinct constructs. Methods: To examine these associations, we conducted a preregistered analysis of 13,490 participants in the Collaborative Study on the Genetics of Alcoholism (COGA). In a structured interview, participants reported their lifetime perpetration of these three aggression phenotypes. Results: The data were better fit by a model that treated these aggression phenotypes as three distinct latent factors, as compared to models in which the items all loaded onto one (‘general’) or two (‘substance-related’ and ‘non-substance-related’) aggression factors. This three factor model fit better for men than women. Subsequent exploratory analyses then showed that among these three factors, alcohol-related aggression explained the variance of overall aggression better than the other two factors. Conclusions: Our findings suggest that these three forms of aggression are distinct phenotypes (especially among men). Yet, people’s alcohol-related aggression can accurately characterize their overall aggressive tendencies across these domains. Future research will benefit from articulating the unique and shared pathways and risk factors underlying each of these facets of aggression.

This study presents findings regarding the prevalence of trauma exposure and Posttraumatic Stress Disorder (PTSD) based on discrete types of trauma (physical, sexual, witnessed violence, and non-assaultive trauma) among 3404 youth in a family study of Alcohol Use Disorder (AUD). Data from the Collaborative Study on the Genetics of Alcoholism (COGA) were used to examine associations of parent AUD with offspring's childhood trauma exposure, and with lifetime diagnosis of DSM-IV PTSD among White and Black participants aged 12-35.Of 3404 youth, 59.7% had parents affected by AUD and 78% experienced <= 1 traumatic event before age 18. AUD in one or both parents was associated with physical, sexual, and witnessed violence among Whites. Among African Americans, maternal AUD was associated with sexual assault. The lifetime PTSD rate among youth exposed to childhood trauma was 8.6%, and mother-only AUD was significantly associated with lifetime PTSD among participants in both groups. PTSD among youth in this study were somewhat higher (7.9% to 8.83%) than those found in general population studies of the same demographic (5% to 6.8%). Maternal AUD appears to be a salient risk factor for sexual assault before age 18 among Black and development of lifetime PTSD among White youth.

Aggression often occurs alongside alcohol and drug misuse. However, it is not clear whether the latent and manifest relations among alcohol-related, drug-related, and non–substance-related aggression are separate manifestations of a single construct or instead are 3 distinct constructs. To examine these associations, we conducted a preregistered analysis of 13,490 participants in the Collaborative Study on the Genetics of Alcoholism. In a structured interview, participants reported their lifetime perpetration of these 3 aggression phenotypes. The data were better fit by a model that treated these aggression phenotypes as 3 distinct latent factors, as compared to models in which the items all loaded onto 1 (“general”) or 2 (“substance-related” and “non–substance-related”) aggression factors. This 3-factor model fit better for men than women. Subsequent exploratory analyses then showed that among these 3 factors, alcohol-related aggression explained the variance of overall aggression better than the other 2 factors. Our findings suggest that these 3 forms of aggression are distinct phenotypes (especially among men). Yet, people’s alcohol-related aggression can accurately characterize their overall aggressive tendencies across these domains. Future research will benefit from articulating the unique and shared pathways and risk factors underlying each of these facets of aggression.

BACKGROUND AND AIMS:Few studies have explored how polygenic propensity to cannabis use unfolds across development, and no studies have yet examined this question in the context of environmental contributions such as peer cannabis use. Outlining the factors that contribute to progression from cannabis initiation to problem use over time may ultimately provide insights into mechanisms for targeted interventions. We sought to examine the relationships between polygenic liability for cannabis use, cannabis use trajectories from ages 12-30 years and perceived peer cannabis use at ages 12-17 years. DESIGN:Mixed-effect logistic and linear regressions were used to examine associations between polygenic risk scores, cannabis use trajectory membership and perceived peer cannabis use. SETTING:United States. PARTICIPANTS:From the Collaborative Study on the Genetics of Alcoholism (COGA) study, a cohort of 1167 individuals aged 12-26 years at their baseline (i.e. first) interview. MEASUREMENTS:Key measurements included life-time cannabis use (yes/no), frequency of past 12-month cannabis use, maximum life-time frequency of cannabis use, cannabis use disorder (using DSM-5 criteria) and perceived peer cannabis use. Polygenic risk scores (PRS) were created using summary statistics from a large (n = 162 082) genome-wide association study (GWAS) of cannabis use. FINDINGS:Three trajectories reflecting no/low (n = 844), moderate (n = 137) and high (n = 186) use were identified. PRS were significantly associated with trajectory membership [P = 0.002-0.006, maximum conditional R2  = 1.4%, odds ratios (ORs) = 1.40-1.49]. Individuals who reported that most/all of their best friends used cannabis had significantly higher PRS than those who reported that none of their friends were users [OR = 1.35, 95% confidence interval (CI) = 1.04, 1.75, P = 0.023]. Perceived peer use itself explained up to 11.3% of the variance in trajectory class membership (OR = 1.50-4.65). When peer cannabis use and the cannabis use PRS were entered into the model simultaneously, both the PRS and peer use continued to be significantly associated with class membership (P < 0.01). CONCLUSIONS:Genetic propensity to cannabis use derived from heterogeneous samples appears to correlate with longitudinal increases in cannabis use frequency in young adults.