# RNA biomarkers for alcohol use disorder

> **NIH NIH K99** · UNIVERSITY OF TEXAS AT AUSTIN · 2024 · $126,309

## Abstract

Next generation sequencing and other -omics technologies have spurred the development of precision
medicine, but this field is still in its infancy for alcohol use disorder (AUD). Transcriptomic studies have
established that alcohol use causes widespread changes in brain gene expression. Brain gene expression
profiles can identify alcohol-dependent human subjects and mice and can be used to repurpose
pharmaceuticals that reduce excessive alcohol consumption in rodents. However, it is not possible to obtain
brain samples from living patients, which limits the translational potential of this approach. Routine blood
testing has long been a part of medical care. Blood genomic profiles could potentially be used to non-invasively
determine whether a patient is at risk for AUD, provide data-driven diagnosis of AUD, stratify the
heterogeneous AUD patient population for clinical trials, select optimal therapy, and monitor treatment
response and disease progression. As a first step toward these goals, Dr. Ferguson analyzed gene expression
patterns in paired blood and brain samples from mice subjected to chronic intermittent ethanol (CIE) exposure,
a mouse model of alcohol dependence. Blood gene expression signatures of CIE predicted a pharmaceutical
that reduced alcohol drinking in mice, and predictive models built from blood profiles distinguished between
CIE and air-exposed mice with high accuracy. These results lead to the hypothesis that blood can serve as a
proxy for brain tissue in molecular-based diagnostic or therapeutic tools and advance personalized medicine
approaches for AUD. However, it is not known whether there is a biological signature of AUD in blood from a
human population. Furthermore, there is a need for biomarkers to predict and monitor treatment success and it
is unknown whether blood gene expression profiles might be useful in this regard. The CIE blood signature
used in the previous study assayed the transcriptome only at a single time point. Therefore, the dynamics or
ongoing transition of important gene regulatory functions were not investigated. These gaps in knowledge will
be addressed in proposed Aims by analyzing blood profiles (1) across multiple time points throughout alcohol
withdrawal in humans (Aim 1), (2) across multiple time points through the development of CIE-induced alcohol
dependence in mice (Aim 2), and (3) before and after treatment in humans and mice (Aim 3). The overarching
hypothesis is that genomic profiles from blood will improve the clinical management of AUD including
diagnosis, prognosis, and predicting treatment response. These Aims and the accompanying training plan
were designed to build on Dr. Ferguson’s previous research experiences and facilitate new scientific training in
clinical alcohol research and biostatistical analyses of longitudinal data, time-to-event outcome data, and
treatment effect estimation. The proposed Pathway to Independence Award will generate new knowledge
about a relatively uns...

## Key facts

- **NIH application ID:** 10930135
- **Project number:** 5K99AA030821-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Laura Brockway Ferguson
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $126,309
- **Award type:** 5
- **Project period:** 2023-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930135

## Citation

> US National Institutes of Health, RePORTER application 10930135, RNA biomarkers for alcohol use disorder (5K99AA030821-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10930135. Licensed CC0.

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