Projects and Grants


VCU Site PI: D. Dick

The Collaborative Study on the Genetics of Alcoholism (COGA) is a tightly integrated and interdisciplinary project that involves participation of investigators from multiple sites spanning a broad range of expertise. The goals of COGA are to identify and characterize genes in which variations confer risk for, or protection from, the development of Alcohol Use Disorders (AUDs) and related phenotypes; to understand the mechanisms by which these variants work at the molecular and cellular level; and to understand how genetic, environmental, and neurocognitive factors interact to influence the developmental trajectories of alcohol use and AUDs through an ongoing prospective study of at-risk individuals. COGA has assembled a unique sample of large, ethnically diverse families densely affected by AUDs and a set of comparison families, with rich phenotypic assessments in multiple domains: clinical, behavioral, neurophysiological, neuropsychological and environmental. The overall specific aims are to: Aim 1. Advance understanding of complex phenotypes related to AUDs; Aim 2. Identify additional genes contributing to risk for AUD, related phenotypes, including endophenotypes; Aim 3. Explore potential mechanisms of action of key genes; Aim 4. Examine effects of genes and environmental influences on clinical and neurophysiological phenotypes related to the vulnerability for risky drinking, AUDs and SUDs across development. In responding to the RFA, the study has three inter-dependent projects and three essential cores. The three projects are each focused on different aspects of these core aims: Genetic and Functional Studies of Alcohol Use Disorders and Related Phenotypes - Using a range of alcohol-related phenotypes, identifies variants across allelic spectrum and studies their mechanisms of action; Prospective Study of Genetic and Environmental Influences on Alcohol Use and Disorders Across Development - Longitudinally studies genetic and environmental influences and their interaction on development of AUDs during adolescence and emerging adulthood; Neurophysiological Phenotypes, Brain Maturation and Development of Alcohol Use and Related Disorders - Identifies genes related to novel neurocognitive phenotypes and their effects on trajectories of neurocognitive development and AUDs. The cores (Administrative Core, Data Management Core, and NIAAA/COGA Sharing Repository Core (NCSR)) provide critical support to each project, ensuring that key cross-study and cross site functions are centralized. Through tight coordination of this interdisciplinary study, we will go from identifyin genes, in which variants affect risk for AUDs and related phenotypes to understanding how they act at multiple levels, from molecular and cellular, to behavioral, neurophysiological, cognitive phenotypic, as a function of development. The delineation of the pathways and genes contributing to alcohol use and AUDs will impact treatment and prevention of AUDs in those at greatest risk.

Other sites (PIs): University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr., T. Foroud); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz); Washington University in St. Louis (L. Bierut, A. Agrawal, J. Rice, K. Bucholz); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield, A. Brooks); University of Texas Medical Center in San Antonio (L. Almasy); Mount Sinai School of Medicine (A. Goate); Howard University (R. Taylor); Virginia Commonwealth University (D. Dick).

Link to NIH RePORT:  U10AA008401 (Porjesz)



PI: D. Dick

This is a competing renewal of "Gene-Environment Interaction in Adolescent Alcohol Use" (R01AA015416), a new investigator research grant that used data from a longitudinal, population-based Finnish twin study to characterize the extent and nature of gene-environment interactions on substance use and externalizing behavior across adolescence. Our analyses demonstrated that etiological factors impacting substance use and externalizing behavior in adolescence vary profoundly as a function of the environment. In this competing renewal, we propose to use data now available on the twins in the young 20s (range 21-27 years) to characterize gene-environment interplay across the transition to young adulthood. The young 20s is a period of critical change as new environments become developmentally relevant (e.g., romantic partnerships, continuation vs. cessation of education, joining the workforce, having children). It also represents a critical time for the development of risky alcohol use behaviors and the onset of problems. This application, prepared by a team of investigators from Virginia Commonwealth University, the University of Helsinki, and Indiana University, has three specific aims. The first aim is to use twin data to characterize gene-environment processes (both gene-environment correlation and interaction) on substance use and externalizing behavior in young adulthood. The second aim is to conduct a series of exploratory analyses aimed at understanding how gene-environment interaction effects identified in twin data can inform our understanding of GxE effects associated with measured genes. We will test whether environments that moderate latent genetic risk in the twin analyses also moderate the association between specific individual genotypic risk and outcome. The third aim is to test the generalizability of identified gene environment interaction effects in a second, independent sample, the Virginia Twin Study of Adolescent Behavioral Development, with phenotypic data collection across a parallel age range from adolescence to young adulthood, and GWAS data. Together, these analyses will advance our understanding of how genetic and environmental influences come together to contribute to substance use patterns during the high-risk young adulthood developmental phase.

In collaboration with Richard Rose (Indiana University) and Jaakko Kaprio (University of Helsinki).

Link to NIH RePORT:  2R01AA015416 (Dick)



MPI: D. Dick/K. Kendler

Pathways to Alcohol Use Disorders in ALSPAC: A Genetic-Developmental Study Alcohol Use Disorders (AUDs) emerge from diverse genetic and environmental risk factors acting through a range of complex developmental pathways. Very few studies exist that have a combination of sample size, representativeness, and sufficiently frequent and detailed assessments over the requisite age range to provide a realistic opportunity to disentangle these intricate etiologic pathways. The Avon Longitudinal Study of Parents and Children (ALSPAC) is such a study. Beginning with over 13,000 pregnant mothers ascertained around Avon England, the ALSPAC project has conducted detailed follow-ups of this sample for the last 16 years. The sample is now entering the critical transitional period from adolescence to young adulthood. This application, prepared by a team of investigators from Virginia Commonwealth University and University of Bristol, has three specific aims in the ALSPAC cohort. The first aim is to add detailed assessments of alcohol use and symptoms of AUDs to questionnaires already scheduled to occur at ages 18 and 20. This will allow us to capture a key developmental phase for alcohol use and the emergence of early symptoms of AUDs. The second aim is to conduct an extensive series of analyses seeking to understand the etiologic pathways to alcohol use (AU) and alcohol use problems (AUPs). The specific goals of these analyses will be (1) to characterize patterns of AU and AUPs across adolescence; (2) to identify childhood risk factors that predict AU and AUPs in adolescence and to understand the developmental processes by which these risks unfold; (3) to study the further development of these risk factors across adolescence and their interaction with emerging AU and its consequences; (4) to test the moderating role of gender on patterns, predictors, and developmental processes related to AU and AUPs; and (5) to extend models of risk for AU and AUPs into young adulthood using the age 18 and 20 data collected under Aim 1. The analyses will examine how risk unfolds across development across three major domains: Externalizing, Internalizing, and Environment (and how these eventually relate to AU and the development of AUPs). Each of these domains is broad, and one of the goals of the project will be to parse these constructs and delineate the most relevant risk dimensions. The third aim of the project is to incorporate information about a limited set of previously validated risk genes into developmental models of risk for AU, AUPs, and AUDs developed in Aim 2. This will be accomplished using molecular genetic data available on at least 3,000 subjects from the ALSPAC cohort at no cost to NIH. These analyses will allow us to study the dynamic interplay of biological, psychological, and social processes that contribute to pathways of risk (and resiliency) for AU and AUPs. With its large sample size, representativeness, detailed and frequent phenotypic assessments and availability of genotypic data, the ALSPAC cohort provides a unique opportunity to clarify, in a developmental context, the complex web of susceptibility and protective factors for AUDs.

In collaboration with Glyn Lewis (University College London) and Matthew Hickman (University of Bristol).

Link to NIH RePORT:  1R01AA018333 (Dick/Kendler)



VCU Site PI: D. Dick

The proposed revised application would continue research on a sample of 999 multiethnic adults who were longitudinally assessed from ages 11-12 to 23-24. Assessment included a CIDI diagnostic interview at age 18-19 and coded videotaped observations of adolescent family and peer interactions. The sample was individually randomized to the Family Check-Up model in adolescence, which yielded long-term effects on drug use, antisocial behavior, depression, and academic success. The proposed follow-up assessment at age 26- 27 would include the CIDI diagnostic interview on addictive behavior and psychopathology, time allocation to high- versus low-investment activities, peer network, self-regulation, and the collection of DNA in saliva samples. Three approaches to genotyping are proposed, including candidate gene, gene family, and novel gene exploration by a team of investigators currently studying the molecular genetics of addictive behavior. These data will be used to address the following hypotheses: (a) the disrupted self-regulation hypothesis, that adult problem behavior generally and addictive behavior specifically are part of an overall pattern of adaptation that is characterized by a low-investment strategy in respect to family relationships and other adult milestones, with low demands on self-regulation; (b) the genetic moderation hypothesis, indicating that the effects of poor parental monitoring and deviant peer exposure on progressions in AOD use and other problem behaviors are most pronounced for youth who are genetically vulnerable; and (c) the risk malleability hypothesis, which proposes that early environmental risk can be modified and that these effects are especially pronounced for genetically prone youth. Testing of all 3 sets of hypotheses requires examination of longitudinal data from early adolescence through age 26-27 that uses a variety of advanced analytic strategies, including trajectory analyses, latent profile analysis, latent growth modeling, and complier average causal effect modeling for examining the effects of the Family Check-Up on risk exposure.   

Additionally, we have formed a collaborative team to continue the study of this sample at age 26–27, during which we will collect saliva samples, analyze DNA, and assess the following constructs: adult adaptation to work, education, and family; psychological adjustment; drug use/abuse; antisocial and criminal behavior; and high-risk sexual behavior. The goal of the present study is to understand how variation in DNA interacts with social factors to contribute to substance use, risk behaviors, and emotional health across the lifespan. The inclusion of DNA in the ongoing longitudinal study will allow us to understand, for example, which genes influence how frequently people drink, or influence why some people are more likely than others to get depressed when they experience a stressful life event.  These data will be used to (a) test developmental progression models of specific alcohol and other drug (AOD) dependence and addictive behavior syndromes, (b) examine biosocial models for the development of AOD use specifically and addictive behavior generally that incorporate molecular genetic indices of susceptibility with peer and family pathogenesis, and (c) examine the long-term effects of the adolescent intervention in moderating genetic susceptibility for addictive behavior.  Longitudinal modeling will capitalize on heterogeneity of growth patterns by using variations of growth mixture modeling.  Furthermore, three approaches to genotyping will be explored; including candidate gene, gene family, and novel gene exploration.  

In collaboration with Thomas Dishion (PI, Arizona State University).

Link to NIH RePORT: 2R01DA007031 (Dishion)



Co-Director: D. Dick

Spit for Science: The VCU Student Survey (VSS) is an effort to understand how genetic and environmental factors come together to contribute to the development of problems associated with the use of alcohol and other substances and emotional health. We aim  to understand how genetic variation, in conjunction with environment factors, contributes to differences in the use of alcohol and other substances, and emotional health.  Starting in 2011 until 2015, for each new freshman cohort, we obtained a completed questionnaire early in the fall of their freshman year and a saliva collection for DNA. Then we obtained a second questionnaire in the spring of their freshman year. Then, for every subsequent year of their college career, we attempted to obtain a follow-up questionnaire in the fall. This included those who remained active students and those who dropped out or eventually graduated.  The questionnaire asks about the student’s personality and behavior, as well as information on family, friends, and experiences growing up.

In collaboration with Kenneth Kendler, support for this project has been provided by 5R37AA011408 (“A Longitudinal Study of Genes, Environment and Alcohol Misuse in College Students”) and through institutional funding.  The 6 specific aims of the NIH grant are: 1) to ascertain new Freshman VCU cohorts in 2012 and 2013 with computer based questionnaires & DNA collections and, along with the 2011 cohort already studied, follow them with yearly surveys up through Fall, 2016. 2) To complete our GWAS analysis of AUDs in the Irish sample and participate in meta-analysis of AUD GWAS sponsored by NIAAA; 3) To conduct extensive epidemiological and longitudinal analyses in the VSS with the goal of clarifying the action and interaction of key risk and protective factors for early problem drinking and to compare and contrast these results with those obtained using parallel measures in the ALSPAC cohort; 4) To genotype the VSS samples using the Affymetrix Biobank v2 array; 5) To screen at the level of SNPs, genes and gene networks, the association between molecular variation in the VSS and risk for early drinking problems and symptoms of AUDs and to compare these results with those obtained with parallel measures in the ALSPAC cohort; 6) To develop models integrating molecular variants and environmental risk factors in predicting early drinking problems and symptoms of AUDs in the VSS.

Link to NIH RePORT:  5R37AA011408 (Kendler)



PI: D. Dick

We propose to design, implement, and assess a university-wide program that integrates research with coursework and programming to create a whole-person educational experience that emphasizes wellbeing as a core component of student success. We will do this through two key avenues: (1) implementation of a campus-wide campaign focused on behavioral and emotional health and wellness via digital and traditional methods, and (2) development of a core course focused on behavioral health and wellness, that draws from the faculty research expertise that exists in this area across VCU, to integrate into the core curriculum. We will collect data from the incoming freshman class during the fall and spring semesters of both years of the proposed project, and compare with extant data collected prior to implementation of the project, in order to assess the effectiveness of the campaign [implemented year 1] and the coursework [implemented year 2] on impacting the wellbeing and academic success of our students.  This project will build upon a unique university-wide longitudinal research project at VCU focused on understanding substance use and emotional health among college students (Spit for Science;, which has enrolled ~70% of the incoming freshman class for the past four years (N=9890), inviting students to complete on-line surveys in the fall of their freshman year and then every spring thereafter.  Through this highly visible, university-wide effort, we have created a community of faculty from multiple departments across the university who conduct research in the area of behavioral and emotional health and wellness, and developed connections between faculty researchers and faculty/staff/administrators involved in health and wellness programming and policy at the university.  This proposal represents the next step in engaging the broader university community (both students and additional faculty/staff around the university) in an effort to have behavioral and emotional health and wellness at the center of the university mission.  We will use the extant research and expertise from our collaborative network to create the content for our wellbeing campaign and coursework.  Further, we will use our deep research expertise to study the effectiveness of the implemented programming on improving outcomes related to health, wellbeing and academic success in our students.

In collaboration with Aradhana Sood, Charles Klink, Barry Falk, Curtis Erwin, Linda Hancock, Gardner Campbell.

Link to BTtoP Awarded Grant



PI: M. Cooke

Risky alcohol use is a major health concern amongst college students, with 40.1% reporting binge drinking (5 or more drinks in one occasion) and 14.4% reporting heavy drinking (binge drinking on 5 or more occasions) in the past month.  Risky alcohol use is thought to be the result of a complex interplay between genes, biological processes, and other phenotypic characteristics. This is further complicated by the phenotypic heterogeneity in the development of alcohol use. Developmental studies have suggested two pathways to risky alcohol use, characterized by externalizing and internalizing characteristics, respectively.  However, the underlying biological processes that differentiate these pathways are not fully understood potentially contributing to the difficulty developing efficacious treatments.  Without this knowledge personalized pharmacological interventions and therapeutic treatments will not be possible.  Neuroimaging studies have assessed reward sensitivity, emotion reactivity, and behavioral inhibition using fMRI and separately demonstrate associations in externalizing and internalizing subtypes.  In addition, previous genetic studies have found associations between specific polymorphisms and these externalizing and internalizing subtypes.  Finally, brain activation patterns have been shown to be a heritable trait themselves.  Therefore, we hypothesize that externalizing and internalizing binge drinkers are characterized by biological differences (at the brain and genome levels) and differences in brain activation mediate the effect of genetic variation on the phenotypic subtype.  We will address this hypothesis through the following Specific Aims: 1) determine the genetic relationship between externalizing and internalizing alcohol subtypes, 2) test whether externalizing and internalizing binge drinkers show differences in brain activation in response to tasks measuring emotion reactivity, reward sensitivity, and/or impulse control and 3) assess the mediation of brain activation on the genetic relationship to each subtype.  In order to achieve these Aims, we will use a large (N~8,000) genotyped young adult sample (NIAAA - R37AA011408, PI Kenneth Kendler) to conduct a series of genotypic analyses assessing differences in common variants, genetic pathways, gene networks, and rare variants between the externalizing and internalizing subtypes.  In a subset of these binge drinking young adults (N=40), brain activation will be measured on tasks assessing behavioral inhibition, reward sensitivity, and emotion reactivity.  Finally, we will test whether variation in brain activation on these tasks mediates the relationship between genetic risk and binge drinking subtype.  The findings of this project will provide solid groundwork to better understand the underlying biology between the classic externalizing and internalizing alcohol use subtypes.  This knowledge of the underlying biology has the potential to elucidate new subtype specific targets for prevention and intervention, a major initiative of the NIAAA.

Link to NIH RePORT: 1F31AA024380 (Cooke)



PI: A. Adkins

Increasing student success is central to the VCU mission and Quest for Distinction strategic plan.  At its simplest level, student success involves academic performance and graduation; at a more holistic level, student success also involves student well-being, which is directly related to positive life outcomes, as emphasized in the recent Gallup report on higher education Great Jobs, Great Lives.  Initiatives to support student success at VCU, in its many forms, are found across the campus, in the shape of advising and programs in the Division of Strategic Enrollment Management, and co-curricular programming (recreational sports, student organizations, career services, etc.) through the Division of Student Affairs.  In addition, we have tremendous faculty research expertise in behavioral and emotional health, as underscored by the newly formed College Behavioral and Emotional Health Institute (COBE;, formal university approval currently under review), which brings together faculty researchers from both campuses to study behavioral and emotional health in college students in order to inform programming related to health and wellness.

Through the Spit for Science project (, a university-wide research opportunity for incoming freshman from 2011-2014, we have enrolled nearly 10,000 students (~70% of freshman the past 4 years), and are following them longitudinally with surveys each spring in order to study student outcomes across the college years. In these surveys we collect information on diverse outcomes, including substance use, depression, anxiety, smoking, eating, family/friends, stressors, sleep, and general health and well-being, with the content collaboratively generated by a team of faculty across the university with diverse expertise related to behavioral and emotional health.  Importantly, we have obtained permission to link this vast amount of self-report data to university level data.  This allows us a unique opportunity to study the connections between student behavioral and emotional health, university engagement in activities and programs, and academic outcomes, such as grades and graduation.  To our knowledge, a project of this magnitude and scope has never been conducted before. 

We can then ask questions such as:  How are student behavioral and mental health outcomes (stress, anxiety, depression, substance use, etc.) associated with academic performance and retention?  Does university engagement (co-curricular activities and support services) modify these associations? How does use of Recreational Sports facilities and programs contribute to students’ outcomes? When looking at the merged data in totality, what are the strongest predictors of retention?  Do these differ for different classes of students (e.g. first generation students, women, minorities, etc)?



PI: J. Savage

The principal aim of this proposed pre-doctoral National Research Service Award (NRSA) application is to support the applicant’s career goal of becoming an independent investigator leading a program of research to understand the genetic and environmental etiology of alcohol misuse and its intersection with internalizing (mood, anxiety disorders) and externalizing (antisocial behavior, illicit drug use) psychopathology. This aim will be achieved through the applicant’s three-fold training goals: 1) obtaining phenotypic expertise in alcohol misuse (and related outcomes); 2) developing methodological skills to elucidate the complex nature of alcohol misuse and the internalizing and externalizing pathways leading to it; and 3) cultivating career and professional development skills. The proposed training plan centers on developing the applicant’s scientific abilities through individualized mentorship, coursework, advanced statistical training, dissemination activities, and, principally, a statistical and molecular genetic study of alcohol misuse. Alcohol misuse, including binge drinking and pathological use, is widespread among college students, and it is associated with many negative public health

outcomes. Despite substantial efforts, researchers have not been able to unequivocally elucidate the genetic and environmental factors underlying alcohol misuse. One explanation for this difficulty is that the phenotypic and underlying genetic architecture of alcohol misuse is heterogeneous – that is, alcohol misuse is not driven by a single set of genetic or environmental causes, but there may be many distinct sets of risk factors contributing to alcohol misuse that differ greatly between individuals. Motives for drinking (e.g. drinking to relieve negative emotions versus drinking to enhance positive emotions) have strong empirical associations with alcohol use behaviors and present a clear mechanism by which divergent genetic and environmental

pathways may influence alcohol misuse. Negative and positive reinforcement drinking motives are related, respectively, to neuroticism and impulsivity, and mirror the schema of a prominent typology that categorizes “internalizing” versus “externalizing” alcoholics. The primary aim of this proposal is to utilize drinking motives to reduce phenotypic complexity and thereby investigate genetic and environmental factors contributing to diverging pathways to alcohol misuse, which we hypothesize correspond to internalizing and externalizing subtypes. To do this, we take advantage of data from a large (N = 9,890), longitudinal, prospective study of college students involving collection of both DNA samples and self-reported phenotypic data. This study design

allows for investigation of biological, psychological, and social aspects of alcohol misuse across an important developmental period. There is a critical need to understand the diverse pathways that can lead individuals to risky or pathological alcohol use in order to alleviate the associated costly and harmful consequences.

Link TBA



PI: J. Salvatore

The scientific objective of this proposal is to examine how alcohol dependence genetic predispositions influence pathways to emerging adulthood (ages 18-29) relationship quality and partner selection, and how characteristics of one’s relationship and partner further shape trajectories of alcohol misuse. The central hypothesis is that gene-environment correlation (rGE) and gene-environment interaction (G x E) processes contribute to these pathways and trajectories. The candidate’s approach leverages novel training in bioinformatics to characterize aggregate genetic risk for alcohol dependence by creating biologically refined polygenic scores. The candidate will then use biologically refined polygenic scores to test gene-environment interplay hypotheses in two NIAAA-funded genetically informative prospective longitudinal studies of emerging adults: Spit for Science (PIs: Dick and Kendler) and the Project Alliance 1 (PAL-1) Relationship Study (PI: Dishion). Spit for Science is a sample of four cohorts of college freshmen (n~10,000) who are followed annually (ages ~18-23). The PAL-1 Relationship

Study is a sample of ~400 romantic dyads (ages ~28-29). One partner in each dyad has been studied since adolescence, and a videotaped couple’s assessment and dyadic longitudinal phenotypic data are collected as part of the relationship study. These studies complement one another in that Spit for Science allows the candidate to examine how the hypothesized gene-environment interplay effects unfold across a six-year period covering the beginning of emerging adulthood, and PAL-1 will provide insights into how the hypothesized effects play out in a specific dyadic relationship in the latter part of emerging adulthood. The three aims of this

work are to: (1) Examine whether alcohol dependence genetic predispositions are associated with the quality of one’s relationship or the alcohol misuse of one’s romantic partner (i.e., rGE), and whether these associations are mediated by antisocial behavior and affiliations with deviant peers in adolescence; (2) Examine whether the quality of one’s relationship or the alcohol misuse of one’s romantic partner moderate alcohol dependence genetic predispositions to predict alcohol misuse (i.e., G x E); (3) Examine whether the patterns observed in Aims 1 and 2 differ by sex. This research is significant because it fills a critical need for studies of gene-environment interplay for alcohol misuse and romantic relationship factors in emerging

adulthood, which is the period of highest risk for the development of alcohol use disorder. Furthermore, the candidate’s proposal to integrate alcohol dependence genome-wide association study results and functional annotation information to develop biologically refined polygenic scores is an innovative departure from the candidate gene approach typically adopted in studies of gene-environment interplay in alcohol research. In summary, the proposed award will provide the candidate with new research and training experiences needed to launch an independent, innovative research program on genetics, romantic relationships, and alcohol

misuse that is relevant to NIAAA’s mission to identify how genetic and salient environmental risk and protective factors for alcohol misuse interface across development.

Link TBA



PI: F. Aliev