Peter B. Barr

(Invited review) genetic research on alcohol use outcomes in African American populations: A review of the literature, associated challenges, and implications

BACKGROUND AND OBJECTIVES There have been remarkable advances in understanding genetic influences on complex traits; however, individuals of African descent have been underrepresented in genetic research. METHODS We review the limitations of existing genetic research on alcohol phenotypes in African Americans (AA) including both twin and gene identification studies, possible reasons for underrepresentation of AAs in genetic research, the implications of the lack of racially diverse samples, and special considerations regarding conducting genetic research in AA populations. RESULTS There is a marked absence of large-scale AA twin studies so little is known about the genetic epidemiology of alcohol use and problems among AAs. Individuals of African descent have also been underrepresented in gene identification efforts; however, there have been recent efforts to enhance representation. It remains unknown the extent to which genetic variants associated with alcohol use outcomes in individuals of European and African descent will be shared. Efforts to increase representation must be accompanied by careful attention to the ethical, legal, and social implications of genetic research. This is particularly true for AAs due to the history of abuse by the biomedical community and the persistent racial discrimination targeting this population. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE Lack of representation in genetic studies limits our understanding of the etiological factors that contribute to substance use and psychiatric outcomes in populations of African descent and has the potential to further perpetuate health disparities. Involving individuals of diverse ancestry in discussions about genetic research will be critical to ensure that all populations benefit equally from genetic advances. (Am J Addict 2017;26:486-493).

Gender orientation and alcohol-related weight control behavior among male and female college students

ABSTRACT Objective: We examine weight control behavior used to (a) compensate for caloric content of heavy alcohol use; and (b) enhance the psychoactive effects of alcohol among college students. We evaluate the role of gender orientation and sex. Participants: Participants completed an online survey (N = 651; 59.9% women; 40.1% men). Method: Weight control behavior was assessed via the Compensatory-Eating-and-Behaviors-in Response-to-Alcohol-Consumption-Scale. Control variables included sex, race/ethnicity, age, and depressive symptoms. Gender orientation was measured by the Bem Sex Role Inventory. The prevalence and probability of alcohol-related weight control behavior using ordinal logistic regression are reported. Results: Men and women do not significantly differ in compensatory-weight-control-behavior. However, regression models suggest that recent binge drinking, other substance use, and masculine orientation are positively associated with alcohol-related weight control behavior. Conclusions: Sex was not a robust predictor of weight control behavior. Masculine orientation should be considered a possible risk factor for these behaviors and considered when designing prevention and intervention strategies.

Post-GWAS in Psychiatric Genetics: A Developmental Perspective on the “Other” Next Steps

As psychiatric genetics enters an era where gene identification is finally yielding robust, replicable genetic associations and polygenic risk scores, it is important to consider next steps and delineate how that knowledge will be applied to ultimately ameliorate suffering associated with substance use and psychiatric disorders. Much of the post‐genome‐wide association study discussion has focused on the potential of genetic information to elucidate the underlying biology and use this information for the development of more effective pharmaceutical treatments. In this review we focus on additional areas of research that should follow gene identification. By taking genetic findings into longitudinal, developmental studies, we can map the pathways by which genetic risk manifests across development, elucidating the early behavioral manifestations of risk, and studying how various environments and interventions moderate that risk across developmental stages. The delineation of risk across development will advance our understanding of mechanism, sex differences and risk and resilience processes in different racial/ethnic groups. Here, we review how the extant twin study literature can be used to guide these efforts. Together, these new lines of research will enable us to develop more informed, tailored prevention and intervention efforts.

Health consequences of same and opposite-sex unions: partnership, parenthood, and cardiovascular risk among young adults

We use the National Longitudinal Survey of Adolescent to Adult Health to examine union and parenthood differences across same and opposite-sex couples in systolic and diastolic blood pressure (SBP and DBP), C-reactive protein (CRP), and abdominal adiposity (waist circumference) among partnered (dating, cohabiting, married) young adults ages 25–33. Relative to women dating men, women cohabiting with women reported lower DBP and were less likely to have high CRP. Mothers reported lower SBP and DBP than non-mothers, but were more likely to have high waist circumference if they lived with a biological or step-child. Among men, nonresidential fathers reported higher DBP than nonfathers, and married men were more likely to have high waist circumference than men dating an opposite-sex partner. Same-sex cohabitation was neither a risk factor nor a health resource for men. Although the sample sizes for same-sex couples are quite small compared with those for opposite-sex couples, this study provides initial insight that occupying a sexual minority status while partnered is associated with some health benefits and few or no health risks relative to those who are dating an opposite sex partner.

Childhood socioeconomic status and longitudinal patterns of alcohol problems: Variation across etiological pathways in genetic risk

Childhood socioeconomic status (SES) is an important aspect of early life environment associated with later life health/health behaviors, including alcohol misuse. However, alcohol misuse is modestly heritable and involves differing etiological pathways. Externalizing disorders show significant genetic overlap with substance use, suggesting an impulsivity pathway to alcohol misuse. Alcohol misuse also overlaps with internalizing disorders, suggesting alcohol is used to cope. These differing pathways could lead to different patterns over time and/or differential susceptibility to environmental conditions, such as childhood SES. We examine whether: 1) genetic risk for externalizing and internalizing disorders influence trajectories of alcohol problems across adolescence to adulthood, 2) childhood SES alters genetic risk these disorders on trajectories of alcohol problems, and 3) these patterns are consistent across sex. We find modest evidence of gene-environment interaction. Higher childhood SES increases the risk of alcohol problems in late adolescence/early adulthood, while lower childhood SES increases the risk of alcohol problems in later adulthood, but only among males at greater genetic risk of externalizing disorders. Females from lower SES families with higher genetic risk of internalizing or externalizing disorders have greater risk of developing alcohol problems.

Alcohol Misuse Across the Life Span: Insights From Developmental Studies in Behavior Genetics

Alcohol misuse, one of today’s greatest public health challenges, is a developmentally dynamic, complex behavior at the intersection of genetic and environmental influences. This review examines such influences from a behavior genetics perspective and discusses implications for public policy. Alcohol misuse is moderately heritable with genetic influences accounting for around 50% of its variance, but to date, few specific genes have been identified. However, numerous environmental and social factors moderate genetic risk, including parents, peers, romantic partners, family dynamics, employment, laws, and cultural influences. These moderating factors change in salience across development, and accordingly, no one-size-fits-all approach is suitable for reducing alcohol misuse at a large scale. We provide examples of some effective prevention and intervention programs and discuss a framework for using the behavior genetics evidence to inform future public policy efforts.

Incorporating Functional Genomic Information To Characterize Polygenic Signal And Identify Variants Enriched For GENE-BY-Environment Interaction For Young Adult Alcohol Problems

Background Polygenic scoring has emerged as one way to characterize aggregate genetic risk; however, the conventional methods for calculating polygenic scores contain a mixture of “true” genetic signal and random noise. We hypothesized that functional genomic information could be used to enhance polygenic signal to predict young adult alcohol use, and to identify genetic variants (single nucleotide polymorphisms; SNPs) likely to be enriched for gene-by-environment interaction. In polygenic analyses in the FinnTwin12 sample, variants located under a DNase I peak or in linkage disequilibrium with a SNP under a DNase I peak (i.e., in an open chromatin region and likely to have a regulatory function) had per-SNP effects that were > 3.5 times higher than non-DNase SNPs. Furthermore, DNase SNPs were enriched for gene-by-environment interaction compared to SNPs filtered by p-value only (p = .047) in tests where romantic relationship status was the environmental moderator. This project examines the use of functional annotation information to improve polygenic risk prediction and the implications for studies of measured gene-environment interaction.