# Single cell transcriptomic study of alcohol use

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $612,749

## Abstract

/// PROJECT SUMMARY \\\
Alcohol use disorder (AUD) is a medical condition characterized by an impaired ability to stop or control alcohol
use despite adverse social, occupational, or health consequences. AUD is common with a 12-month and
lifetime prevalence in the US of 13.9% and 29.1%, respectively. Gene expression studies provide promising
opportunities to better understand AUD etiology. As cells differ in their function, gene expression will typically
also differ across cell-types. When studying bulk tissue, failure to account for cell diversity has a detrimental
impact on the ability to detect disease associations. For example, case-control differences will be “diluted” if
they affect only one cell-type, may cancel out if the differences are of opposite signs across cell-types, and
may be undetectable if the differences involve low abundance cells. Furthermore, identifying the specific cell-
types from which the association signals originate is key to formulating refined hypotheses of AUD etiology,
designing proper follow-up experiments and, eventually, developing novel clinical interventions.
 Our overall goal is to perform a rigorous study in post-mortem brain samples to detect differentially
expressed genes in AUD at a fine-grained cellular level, and identify the genetic elements that regulate these
differences. To achieve this goal, we propose a strategy that has become available with the recent evolution of
single nucleus RNA sequencing (snRNA-seq) technology that can characterize the expression levels of
thousands of individual nuclei with a single reaction. Our pilot data shows that our lab is able to produce
snRNA-seq data of the highest quality and illustrates the promise of snRNA-seq to detect biologically relevant
findings. Using careful selection procedures, we obtained a unique collection of relatively severe cases that
were diagnostically homogenous while having minimal comorbidities, and that were matched to the controls on
key variables. We will focus on three brain regions that are heavily implicated in AUD and capture different
aspects of the disease. Study design features were guided by a series of power analyses that are grounded in
empirical observations from our pilot study. To ensure robust results, findings will be replicated using snRNA-
seq data from independent individuals and validated with a different technology. Finally, we propose a series of
follow-up analyses aimed at identifying potential regulators of replicating findings, (functionally) characterizing
existing robust AUD GWAS associations, and detecting blood biomarkers of AUD disease processes in brain.
 Successful completion of this project will yield (i) unprecedented insights into AUD disease mechanisms,
(ii) possible blood biomarkers of genes differentially expressed in brain, and (iii) lay the foundation for
functional follow-up studies and, eventually, novel highly specific clinical interventions for improving AUD
treatment.

## Key facts

- **NIH application ID:** 10916177
- **Project number:** 5R01AA030116-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Karolina Anna Aberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $612,749
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916177

## Citation

> US National Institutes of Health, RePORTER application 10916177, Single cell transcriptomic study of alcohol use (5R01AA030116-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10916177. Licensed CC0.

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