Project Details
Description
Project Summary
This project has two complementary goals: (1) to advance discovery of genes involved in
substance use disorders using new multivariate genomic techniques, and (2) to characterize the
risk associated with identified variants in diverse longitudinal samples in order to understand the
spectrum of phenotypes associated with identified variants, across development, and in
conjunction with the environment. Each of these areas represents critical steps in using genetic
data to improve prevention, intervention, and treatment for substance use disorders (SUDs),
and will lay the foundation as we move into an era of personalized medicine. Human gene
identification efforts for substance use disorders lag behind other areas of psychiatry, in part
due to constrained sample sizes of available SUD cases. However, recent meta-analyses of
substance-related phenotypes such as age of initiation, consumption and problems, reveal
significant genetic correlations across substance use outcomes, as well as with numerous other
psychiatric and behavioral traits. These findings map onto twin data demonstrating significant
genetic correlations across substance use disorders and other externalizing traits. This project
will (Aim 1) apply new multivariate genetic methods to capitalize on genetic sharing between
substance use phenotypes and related traits in order to boost power to detect common variants
associated with substance use outcomes, and to characterize the latent pathways by which
genetic variants operate. Bioinformatic characterization of these identified genetic variants will
provide insight into underlying biological risk pathways, and phenotypic characterization of
resultant polygenic risk scores will help us understand how risk unfolds across development and
in conjunction with the environment. We will apply results from the multivariate analyses to two
complementary longitudinal datasets, consisting of a population-based and high-risk sample, in
order to (Aim 2a) map the behavioral phenotypes associated with the genetic risk scores
identified in Aim 1 across adolescence and emerging adulthood; (Aim 2b) test for pathways of
risk specific to sex and racial/ethnic background; and (Aim 2c) test for moderation of genetic risk
by key environmental factors. Jointly, these analyses will advance our understanding of how
genetic variation contributes to risk for substance use disorders.
Status | Active |
---|---|
Effective start/end date | 7/1/20 → 4/30/25 |
Funding
- National Institute on Drug Abuse: $588,712.00
- National Institute on Drug Abuse: $554,862.00
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