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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.

Genetic factors contribute to the intergenerational transmission of alcohol misuse, but not all individuals at high genetic risk develop problems. The present study examined adolescent relationships with parents, peers, and romantic partners as predictors of realized resistance, defined as high biological risk for disorder combined with a healthy outcome, to alcohol initiation, heavy episodic drinking, and alcohol use disorder (AUD). Data were from the Collaborative Study on the Genetics of Alcoholism (N = 1,858; 49.9% female; mean age at baseline = 13.91 years). Genetic risk, indexed using family history density and polygenic risk scores for alcohol problems and AUD, was used to define alcohol resistance. Adolescent predictors included parent-child relationship quality, parental monitoring, peer drinking, romantic partner drinking, and social competence. There was little support for the hypothesis that social relationship factors would promote alcohol resistance, with the exception that higher father-child relationship quality was associated with higher resistance to alcohol initiation ( $$\hat \beta $$ = −0.19, 95% CI = −0.35, −0.03). Unexpectedly, social competence was associated with lower resistance to heavy episodic drinking ( $$\hat \beta $$ = 0.10, 95% CI = 0.01, 0.20). This pattern of largely null effects underscores how little is known about resistance processes among those at high genetic risk for AUD.

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=4045) and African ancestry (AA, n=1550) individuals from the multigenerational COGA sample (56% female, M(age) ~ 41 years). Outcomes were lifetime marriage and divorce. Predictors included lifetime AUD, an alcohol problems polygenic score, and AUD comorbidities, including 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 [HR] 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, p < 0.01). Among EA participants, AUD, CAN, TOB, and MDD were associated with higher odds of divorce (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, alcohol use disorder was associated with reduced likelihood of marriage in European and African ancestry individuals, and increased risk of divorce in European ancestry individuals. These associations were largely independent of comorbidities. Genetic and environmental background factors contributed to marriage, while only environmental background factors contributed to divorce.

Aim This study presents a measure of Social Recovery Capital (SRC) derived from the Important People and Activities instrument (IPA). Methods The sample comprised young adults who participated in the Collaborative Study on the Genetics of Alcoholism, a high-risk family study of alcohol use disorder (N = 2472). Exploratory and confirmatory factor analysis identified influential items and factor structure, adjusting for family relatedness. The final scale was tested for reliability and validity. Results Factor analysis retained 10 items loading on three factors (Network Abstinence Behaviors, Basic Network Structure and Network Importance) that together explained 42% of the variance in SRC. The total model showed adequate fit (Comparative Fit Index = 0.95; Tucker Lewis Index = 0.93; Root Mean Square Error of Approximation = 0.06; Standardized Root Mean Squared Residual = 0.05) and acceptable reliability (α = 0.60; McDonald’s ω = 0.73) and correlated with validation measures mostly in the weak to moderate range. Due to variable factor scores for reliability and validity, we only recommend using the total score. Conclusion The SRC-IPA is a novel measure of SRC derived from the IPA that captures social network data and has applications in research and clinical work. Secondary data analyses using the SRC-IPA in studies that collected the IPA can further demonstrate the interaction of SRC with a wide variety of clinical indicators and demographic characteristics, making it a valuable addition to other measures of SRC.

Introduction: The utility of genetic risk information relies on the assumption that individuals will use the information to change behavior to reduce risk for developing health problems. Educational interventions designed to target elements of the Health Belief Model have shown to be effective in promoting behaviors for positive outcomes. Methods: A randomized controlled trial (RCT) was conducted in 325 college students to assess whether a brief, online educational intervention altered elements of the Health Belief Model that are known to be associated with motivations and intentions to change behavior. The RCT included a control condition, an intervention condition that received information about alcohol use disorder (AUD), and an intervention condition that received information about polygenic risk scores and AUD. We used t-tests and ANOVA methods to compare differences in beliefs related to the Health Belief Model across study conditions and demographic characteristics. Results: Providing educational information did not impact worry about developing AUD, perceived susceptibility and severity of developing alcohol problems, or perceived benefits and barriers of risk reducing actions. Individuals in the condition that received educational information about polygenic risk scores and AUD reported higher perceived chance of developing AUD than individuals in the control condition (adj. p < .01). Sex, race/ethnicity, family history, and drinking status were associated with several components of the Health Belief Model. Conclusion: Findings from this study demonstrate the need to better design and refine the educational information intended to accompany the return of genetic feedback for AUD to better promote risk-reducing behaviors.

IntroductionAs gene identification efforts have advanced in psychiatry, so have aspirations to use genome-wide polygenic information for prevention and intervention. Although polygenic risk scores (PRS) for substance use and psychiatric outcomes are not yet available in clinical settings, individuals can access their PRS through online direct-to-consumer resources. One of these widely used websites reports that alcohol use disorder is the third most requested PRS out of >1,000 conditions. However, data indicate that there are misunderstandings about complex genetic concepts, with a lower understanding of PRS being associated with a more negative impact of receiving polygenic risk information. There is a need to develop and evaluate educational tools to increase understanding of PRS.MethodsWe conducted a randomized controlled trial to evaluate the impact of web-based educational information on understanding of PRS for alcohol use disorder. A total of 325 college students (70.4% female; 43.6% White; mean age = 18.9 years) from an urban, diverse university completed the study.ResultsOverall, participants were highly satisfied with the educational information. Results from a one-way ANOVA indicated that there was a significant increase in overall understanding of PRS for alcohol use disorder (p-value < 0.001), among individuals who received educational information about PRS and alcohol use disorder, as compared to receiving no accompanying information (adj. p-value < 0.001), or educational information about alcohol use disorder only (adj. p-value < 0.001).DiscussionThese findings suggest that the web-based educational tool could be provided alongside polygenic risk information in order to enhance understanding and interpretation of the information.Clinical trial registration[ClinicalTrials.gov], identifier [NCT05143073].

Genome-wide association studies aim to identify genetic variants that are associated with a disease phenotype in order to enhance precision medicine efforts. Despite the excitement surrounding the promise of precision medicine and interest among the public in accessing personalized genetic information, there has been little effort dedicated to understanding how complex genetic risk information could be incorporated into clinical practice to inform prevention, screening, and treatment. In this article, we briefly summarize the literature on the impact of receiving genetic risk information on health-related behavior, discuss the limitations of these studies, and outline the challenges that will need to be overcome, along with suggested next steps for future studies, to understand the true promise of precision medicine. The current literature demonstrates that there is no consistent or strong evidence that receiving complex genetic risk information, such as polygenic risk scores, has an impact on behavior; however, there are a number of limitations that may impact the failure to find significant effects associated with receiving genetic feedback. Behavior change is a complex process and simply providing genetic risk information without incorporating a theoretical perspective on behavior change diminishes the potential impact of receiving genetic risk information on actual behavior change. Future studies and interventions which return genetic feedback should be designed using theoretical frameworks of behavior change models to improve the impact of receiving personalized genetic information.The basis of precision medicine is to use an individual’s personal genetic information, such as a polygenic risk score, along with lifestyle information and personal medical history, to promote better health outcomes. The utility of polygenic risk scores relies on the assumption that receiving complex genetic feedback will motivate changes in behavior that reduces one’s risk for developing a medical condition. To date, there is no consistent or strong evidence that receiving complex genetic risk information, such as polygenic risk scores, influences behavior change. However, the literature on how to effectively deliver polygenic risk scores is small. Prior studies assessing the impact of receiving complex genetic risk information have several limitations that may impact the failure to find that individuals take action or change health behaviors after receiving genetic feedback. One way to address these limitations is to incorporate theories of behavior change, such as the Health Belief Model, into the way in which genetic risk information is returned. Designing intervention programs grounded in theories of behavior change and developing testable hypotheses related to theoretical mechanisms of change are important next steps.

Higher parental educational attainment is associated with higher offspring educational attainment. In this study, we incorporated genotypic and phenotypic information from fathers, mothers, and offspring to disentangle the genetic and socioenvironmental pathways underlying this association. Data were drawn from a sample of individuals of European ancestry from the collaborative study on the genetics of alcoholism (

Transitioning to college during the novel coronavirus disease 2019 (COVID-19) pandemic may increase risk for alcohol use and mental health problems. We examined how COVID-19 related stressors and parent-child relationships are independently and interactively associated with alcohol use and mental health profiles in a sample of first-year college students (N = 425, 34.8% Hispanic/Latinx; 74.9% female) who completed an online survey in October 2020. Latent profile analysis identified four profiles: well-adjusted (53.2%), mental health problems only (21.6%), alcohol use only (17.4%), and comorbid (7.8%). COVID-19 related stressful events increased risk of being in the alcohol use only and comorbid profiles, whereas COVID-19 related worries increased risk of being in the mental health problems only profile. Parent-child relationship quality lowered risk of being in the mental health problems only and the comorbid profiles. In addition, parent-child relationship quality moderated the role of COVID-19 related worries such that COVID-19 related worries were associated with lower odds of being in the comorbid profile when parent-child relationship quality was high but not when parent-child relationship quality was low. Strengthening parent-child relationship quality appears important for promoting college students' well-being.

Substance use disorders (SUDs) incur serious social and personal costs. Risk for SUDs is complex, 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 = 2,475) 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 = 1.37 – 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.

Background This study examined whether polygenic risk scores (PRS) for lifetime cannabis and alcohol use were associated with misusing opioids, and whether sex differences existed in these relations in an urban, African-American sample. Methods Data were drawn from three cohorts of participants (N = 1,103; 45% male) who were recruited in first grade as part of a series of elementary school-based, universal preventive intervention trials conducted in a Mid-Atlantic region of the U.S. In young adulthood, participants provided a DNA sample and reported on whether they had used heroin or misused prescription opioids in their lifetime. Three substance use PRS were computed based on prior GWAS: lifetime cannabis use from Pasman et al. (2018), heavy drinking indexed via maximum number of drinks from Gelernter et al. (2019), and alcohol consumption from Kranzler et al. (2019). Results Higher PRS for lifetime cannabis use, greater heavy drinking, and greater alcohol consumption were associated with heightened risk for misusing opioids among the whole sample. Significant sex by PRS interactions were also observed such that higher PRS for heavy drinking and alcohol consumption were associated with a greater likelihood of opioid misuse among males, but not females. Conclusion Our findings further elucidate the genetic contributions to misusing opioids by showing that the genetics of cannabis and alcohol consumption are associated with lifetime opioid misuse among young adults, though replication of our findings is needed.

Experiences of racial discrimination have been shown to increase risk for alcohol problems. Some individuals may be particularly vulnerable to the negative effects of racial discrimination. However, little research has examined interaction effects between racial discrimination and individual characteristics, such as genetic predispositions and personality, in relation to alcohol outcomes. This study examined whether genetic risk and dimensions of impulsivity moderate the association between racial discrimination and alcohol problems among African American young adults (n = 383, M

This study investigated youth’s modeling of and de-identification from parents in romantic relationships, using two phases of data from adolescent siblings, mothers, and fathers in 246 Mexican-origin families. Each parent reported his/her marital satisfaction and conflict, and youth reported on parent-adolescent warmth and conflict at Time 1. Youth’s reports of modeling of and de-identification from their mothers and fathers and three romantic relationship outcomes were assessed at Time 2. Findings revealed that higher parental marital satisfaction, lower marital conflict, and higher warmth and lower conflict in parent-adolescent relationships were associated with more modeling and less de-identification from parents. Moreover, higher de-identification was linked to a greater likelihood of youth being involved in a romantic relationship and cohabitation, whereas more modeling was linked to a lower likelihood of cohabitation and older age of first sex. Discussion underscores the importance of assessing parental modeling and de-identification and understanding correlates of these processes.

Parental alcohol use disorders (AUDs) and parental separation are associated with increased risk for early use of alcohol in offspring, but whether they increase risks for early use of other substances and for early sexual debut is under-studied. We focused on associations of parental AUDs and parental separation with substance initiation and sexual debut to (1) test the strength of the associations of parental AUDs and parental separation with time to initiation (age in years) of alcohol, tobacco and cannabis use and sexual debut and (2) compare the strength of association of parental AUD and parental separation with initiation.Prospective adolescent and young adult cohort of a high-risk family study, the Collaborative Study on the Genetics of Alcoholism (COGA).Six sites in the United States.A total of 3257 offspring (aged 14-33 years) first assessed in 2004 and sought for interview approximately every 2 years thereafter; 1945 (59.7%) offspring had a parent with an AUD.Diagnostic interview data on offspring substance use and sexual debut were based on first report of these experiences. Parental life-time AUD was based on their own self-report when parents were interviewed (1991-2005) for most parents, or on offspring and other family member reports for parents who were not interviewed. Parental separation was based on offspring reports of not living with both biological parents most of the time between ages 12 and 17 years.Parental AUDs were associated with increased hazards for all outcomes, with cumulative hazards ranging from 1.19 to 2.71. Parental separation was also an independent and consistent predictor of early substance use and sexual debut, with hazards ranging from 1.19 to 2.34. The strength of association of parental separation with substance initiation was equal to that of having two AUD-affected parents, and its association with sexual debut was stronger than the association of parental AUD in one or both parents.Parental alcohol use disorders (AUDs) and parental separation are independent and consistent predictors of increased risk for early alcohol, tobacco and cannabis use and sexual debut in offspring from families with a high risk of parental AUDs.