# Systems Genetics of Cocaine Preference in Drosophila

> **NIH NIH F31** · CLEMSON UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Cocaine Use Disorder (CUD) represents a significant public health and socioeconomic concern. Cocaine is
involved in 40% of drug-related emergency room visits, and rates of cocaine overdose in the United States are
climbing steadily. Yet, the genetic underpinnings that predispose to CUD remain poorly understood. Twin studies
on the genetics of CUD provide heritability estimates between 42-79%. However, significant heritability estimates
do not indicate which genes are involved, and how they might be functionally relevant. Genome-wide association
studies (GWAS) of CUD are limited by inability to control environmental factors; the haplotype structure of the
human genome limiting mapping precision; and small sample sizes due to difficulty recruiting participants
because of criminalization of cocaine use. Model organisms such as the fruit fly Drosophila melanogaster offer
a cost-effective alternative where sample size, environment, and genetic background can be controlled. Cocaine
binds to the dopamine transporter of Drosophila as it does in humans, eliciting cocaine-induced locomotor
phenotypes. GWAS in Drosophila are facilitated by the Drosophila melanogaster Genetic Reference Panel
(DGRP), an expanding collection of wild-derived, inbred, fully sequenced lines that provide a living library of
natural variation. It is my goal to use the DGRP and a systems genetics approach to uncover the genetic
underpinnings of cocaine-related phenotypes. In Specific Aim 1, I will investigate the impact of genetic
background on cocaine preference by screening 600 DGRP lines for cocaine preference using the microplate
feeder assay. I will then perform a GWAS, utilizing whole genome sequence data to identify genetic variants
associated with cocaine preference. I will perform gene ontology and KEGG orthology pathway enrichment
analyses, as well as construct genetic interaction networks to implicate genes and pathways involved in cocaine
preference. In Specific Aim 2, I will quantify the behavioral and transcriptomic effects of cocaine exposure in
DGRP lines with extreme cocaine preference. For 25 DGRP lines that exhibit cocaine preference and 25 lines
near the population average, I will assess effects of cocaine on sensorimotor integration upon repeated
exposures. In Specific Aim 3, I will functionally validate candidate genes and variants associated with cocaine
preference using RNA interference and out-of-sample testing of DGRP lines, respectively. Completion of these
aims will result in a systems genetics model of cocaine preference in Drosophila with translational potential for
human cocaine use disorder. This project will train me in advanced systems genetics techniques and analyses
and prepare me for a professional career in the study of the genetics of substance use disorders.

## Key facts

- **NIH application ID:** 10891421
- **Project number:** 5F31DA057062-02
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Jeffrey S Hatfield
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-09-08 → 2025-09-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891421

## Citation

> US National Institutes of Health, RePORTER application 10891421, Systems Genetics of Cocaine Preference in Drosophila (5F31DA057062-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10891421. Licensed CC0.

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