The Mechanisms Underlying the Intergenerational Transmission of Substance Use and Misuse: An Integrated Research Approach.

Substance use and substance use disorders run in families. While it has long been recognized that the etiology of substance use behaviors and disorders involves a combination of genetic and environmental factors, two key questions remain largely unanswered: (1) the intergenerational transmission through which these genetic predispositions are passed from parents to children, and (2) the molecular mechanisms linking genetic variants to substance use behaviors and disorders. This article aims to provide a comprehensive conceptual framework and methodological approach for investigating the intergenerational transmission of substance use behaviors and disorders, by integrating genetic nurture analysis, gene expression imputation, and weighted gene co-expression network analysis.

Comorbidity and sex differences in functional disorders and internalizing disorders.

Objective: In the current exploratory study we estimate comorbidity rates between FDs [fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and irritable bowel syndrome (IBS)]-and IDs-[major depressive disorder (MDD) and generalized anxiety disorder (GAD)] by using self-reported diagnostic criteria.

Method: We analyzed data from 107,849 participants (mean age = 49.3 (SD = 13.

A Developmentally-Informative Genome-wide Association Study of Alcohol Use Frequency.

Contemporary genome-wide association study (GWAS) methods typically do not account for variability in genetic effects throughout development. We applied genomic structural equation modeling to combine developmentally-informative phenotype data and GWAS to create polygenic scores (PGS) for alcohol use frequency that are specific to developmental stage. Longitudinal cohort studies targeted for gene-identification analyses include the Collaborative Study on the Genetics of Alcoholism (adolescence n = 1,118, early adulthood n = 2,762, adulthood n = 5,255), the National Longitudinal Study of Adolescent to Adult Health (adolescence n = 3,089, early adulthood n = 3,993, adulthood n = 5,149), and the Avon Longitudinal Study of Parents and Children (ALSPAC; adolescence n = 5,382, early adulthood n = 3,613).

Association of parental divorce, discord, and polygenic risk with children's alcohol initiation and lifetime risk for alcohol use disorder.

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.

Genetic nurture effects for alcohol use disorder.

We tested whether aspects of the childhood/adolescent home environment mediate genetic risk for alcohol problems within families across generations. Parental relationship discord and parental divorce were the focal environments examined. The sample included participants of European ancestry (N = 4806, 51% female) and African ancestry (N = 1960, 52% female) from the high-risk Collaborative Study on the Genetics of Alcoholism.

Principal Component Analysis Reduces Collider Bias in Polygenic Score Effect Size Estimation.

In this study, we test principal component analysis (PCA) of measured confounders as a method to reduce collider bias in polygenic association models. We present results from simulations and application of the method in the Collaborative Study of the Genetics of Alcoholism (COGA) sample with a polygenic score for alcohol problems, DSM-5 alcohol use disorder as the target phenotype, and two collider variables: tobacco use and educational attainment. Simulation results suggest that assumptions regarding the correlation structure and availability of measured confounders are complementary, such that meeting one assumption relaxes the other.

Alcohol use disorder, psychiatric comorbidities, marriage and divorce in a high-risk sample.

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; = 4,045) and African ancestry (AA; = 1,550) individuals from the multigenerational Collaborative Study on the Genetics of Alcoholism (COGA) sample (56% female, ∼ 41 years). Outcomes were lifetime marriage and divorce.

Associations between the CADM2 gene, substance use, risky sexual behavior, and self-control: A phenome-wide association study.

Risky behaviors, such as substance use and unprotected sex, are associated with various physical and mental health problems. Recent genome-wide association studies indicated that variation in the cell adhesion molecule 2 (CADM2) gene plays a role in risky behaviors and self-control. In this phenome-wide scan for risky behavior, it was tested if underlying common vulnerability could be (partly) explained by pleiotropic effects of this gene and how large the effects were.

Cannabis use in college: Genetic predispositions, peers, and activity participation.

Background: Among adult college students in the US, cannabis use is common and associated with considerable negative consequences to health, cognition, and academic functioning, underscoring the importance of identifying risk and protective factors. Cannabis use is influenced by genetic factors, but genetic risk is not determinative. Accordingly, it is critical to identify environments that reduce risk among those who are at elevated genetic risk.

E-cigarette use is prospectively associated with initiation of cannabis among college students.

E-cigarettes have dramatically increased in popularity among youth. Coincident with expanded legalization, young adults' use of cannabis (marijuana) has also steadily increased in recent years. Use of tobacco products can increase the chances of later cannabis initiation among youth.

Alcohol Metabolizing Polygenic Risk for Alcohol Consumption in European American College Students.

Objective: Evidence suggests that the nature and magnitude of some genetic effects on alcohol use vary by age. We tested for moderation in the effect of an alcohol metabolizing polygenic score by time across the college years.

Method: Participants (total n = 2,214) were drawn from three cohorts of undergraduate college students, who were assessed annually for up to 4 years starting in their freshman year.

The role of romantic relationship status in pathways of risk for emerging adult alcohol use.

Dating several people in emerging adulthood has been associated with higher alcohol use compared with being single or being in an exclusive relationship. As a follow-up to that report, we examined whether romantic relationship status is part of a pathway of risk between antecedent alcohol use risk factors and subsequent alcohol outcomes. Participants were 4,410 emerging adults assessed at 2 time-points during their first year of college.