Review of NIDA's Portfolio of Research on the Genetic Epidemiology of Drug Abuse

United States

NIDA Organizers: Naimah Weinberg, M.D., DESPR

Meeting Purpose and Intent:

To review recent findings in the genetic epidemiology of drug abuse; strengths, weaknesses, and gaps in the current research portfolio; and opportunities for cost-effective and translational approaches in the future.

Brief Discussion of Meeting Outcome:

Invited experts on genetic epidemiology of drug abuse reviewed recent findings, evaluated the strengths and weaknesses of NIDA's current research portfolio, and offered recommendations on important gaps and approaches for filling them. They also discussed translational implications and a future meeting to bridge the various disciplines. Advances, gaps, and opportunities converged on five major areas:

Methodology and statistics: NIDA-funded genetic epidemiologic studies have generated a great deal of strong, developmentally informed data; now NIDA needs to encourage more methodologic studies and attract and train sophisticated, dedicated biostatisticians and methodologists to develop and apply state of the art approaches to existing data. Issues to consider include the conditionality of drug use disorders on drug exposure and methods for combining data across studies to increase power. More work on nosology, causal modeling, quantitative approaches, and testing alternative models are merited. Addressing issues impeding data collection, such as developing web-based data collection methods, improving the quality and validity of retrospective data, and resolving issues related to use of secondary informants, are germane to this topic as well.

Development and trajectories: Important advances have been made in understanding the development of drug use disorders through genetic epidemiologic research, including familial transmission, contributions of environmental and genetic factors to different stages of drug use and progression, characterization of a disinhibited phenotype, and the potential significance of horizontal transmission of drug use among sibs and peers. Numerous gaps remain, including transitions among stages of use and dependence, different trajectories of drug abuse (from one drug to another, persistence, desistance, resilience, and relapse), gender differences, and the relative roles of environmental, genetic, and physiological factors (such as early puberty). Clarifying the role of early use as a marker or causal risk factor has important implications for prevention.

Social/environmental: In contrast to other behavioral disorders, research suggests that shared environment plays an important role in the onset of drug use. Further studies need to explicate the role of gene environment interactions, and gene-environment correlations need to be better understood for targeting preventive interventions appropriately, and for better understanding how individuals influence and select their environments. Moreover, gene-environment correlations need to be clarified in order to accurately identify gene-environment interactions. Other areas meriting further study include the roles of in utero exposure, trauma, ethnic variation and broader social factors.

Phenotypes/endophenotypes: One of the strengths of the current portfolio is the inclusion of studies of endophenotypes and of alternative phenotypes to the DSM system, such as personality traits and comorbidity. However, more research is needed on delineating brain mechanisms underlying these behaviors; affective neuroscience; endophenotypes that extend beyond electrophysiology; startle modulation endophenotypes; behavioral inhibition and affective phenotypes; the addiction to sedating drugs; sleep endophenotypes.

Translational applications: Genetic epidemiologic approaches can greatly inform etiology, nosology, prevention, treatment, gene-finding and other molecular research. Gene-finding can be improved with advances in phenotyping, nosology, and gene-environment interaction. Studies of evocative vs. passive gene-environment correlations have strong implications for prevention, and genetic epidemiology studies can help identify which environmental factors to target for intervention, and when such interventions are likely to be most effective. Genetic epidemiologic studies of relapse and desistance have implications for treatment. Genetic epidemiologic studies are better positioned among etiology studies to distinguish causal from correlational associations.

Expected Follow-up:

Findings and recommendations will be incorporated into a revised Program Announcement on the Genetic Epidemiology of Substance Use Disorders, and into other announcements and program planning.

Brief Description of Resulting Publications: none currently