# Leveraging genetic and electronic health record data to identify novel targets and drugs for treating alcohol use disorder

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2022 · $553,341

## Abstract

PROJECT SUMMARY/ABSTRACT
While four medications for treating alcohol use disorder (AUD) are approved by the Food and Drug Administration
(FDA), many patients do not benefit from them. Moreover, while genome-wide association studies (GWASs) of
alcohol consumption and problematic alcohol use (PAU; i.e., a phenotype that combines AUD diagnoses and a
measure of harmful drinking) have yielded many significant single nucleotide polymorphisms (SNPs) that affect
risk, these have yielded few drug targets for treating AUD. Hence, there is an unmet need to identify drug targets
for the development of novel and/or repurposed drugs to treat AUD. Recent research indicates that targeting
disease mechanisms with genetic support can increase the success rate in drug development and that modules
(i.e., biological networks surrounding disease-associated genes) are enriched for targets of approved drugs.
Thus, genes affecting alcohol consumption and risk of PAU and their associated modules could yield new targets
and drugs for therapeutic repurposing. Furthermore, the availability of large electronic health records (EHR)
datasets makes it possible to explore whether exposure to FDA-approved drugs can lead to improvements in
medical conditions other than the ones for which they are approved, such as AUD, and potentially be repurposed.
This proposal will build upon prior work by the study team and leverage advances in genomics and access to
the Veterans Affairs (VA) EHR through the VA Informatics and Computing Infrastructure (VINCI) to: 1) elucidate
modules linked to alcohol consumption and PAU (Aims 1 and 3); and 2) identify promising drugs for repurposing
to treat AUD (Aim 2). The general hypotheses for Aims 1-2 are: 1) the genes implicated in the identified modules
will be targeted by numerous approved drugs; and 2) of the drugs with sufficient patient data in the VA EHR,
there will be evidence that they reduce alcohol consumption in propensity score analyses. The hypothesis for
Aim 3 is that the analysis will identify top ranked modules that are enriched for biological processes with
relevance to alcohol consumption and PAU. In sum, this proposal combines psychiatric genetic and
pharmacoepidemiologic methods to identify novel targets and evaluate promising drugs to be repurposed for
treating AUD. An atheoretical, genetic data-driven approach to selecting promising FDA-approved drugs and
then testing them in the EHR using propensity score methods has not previously been done in psychiatry,
including for AUD. This project is made possible by recent advances in GWAS of alcohol consumption and PAU,
drug target linking, and the cultivation of EHRs for genetic and other analyses. This approach to drug prioritization
could uncover unique drugs to be tested in follow-up clinical trials and novel targets to be evaluated in preclinical
studies.

## Key facts

- **NIH application ID:** 10418259
- **Project number:** 1R01AA030041-01
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Joshua Charles Gray
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $553,341
- **Award type:** 1
- **Project period:** 2022-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418259

## Citation

> US National Institutes of Health, RePORTER application 10418259, Leveraging genetic and electronic health record data to identify novel targets and drugs for treating alcohol use disorder (1R01AA030041-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10418259. Licensed CC0.

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