# Identification and Characterization of Novel Genetic Mechanisms in Alcohol Use Disorder and Excessive Drinking

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $162,523

## Abstract

Project summary/abstract
Alcohol use disorder (AUD) is associated with significant costs to both the individual and society. Genetic and
environmental factors contribute to the risk of AUD and excessive drinking, and a better understanding of the
specific risk genes will allow for novel strategies for prevention and treatment. Recent well-powered human
genome wide association studies (GWAS) of AUD and alcohol consumption have begun to identify multiple
novel candidate genes. As increasing numbers of genes are implicated, it will be imperative to have
researchers trained to work at the interface between human and animal model research. This will allow for the
translation of genetic findings across organisms for follow-up and characterization of novel genetic
mechanisms. This proposal involves training in two converging strategies for translational genetic research in
AUD and excessive drinking. Aim 1 will provide training in prioritizing genetic hits from human GWAS for
follow-up in animal studies using new mutant mouse lines. The goal of Aim 1 is to move from identification of
genes in GWAS to mechanistic characterization using mouse models. Mutant mouse lines developed based on
GWAS hits will be evaluated on a variety of behavioral assays to identify which aspects of drinking behavior
are altered by the genetic manipulation; the ultimate goal of these studies will be to develop an optimized
behavioral framework for assessing gene effects on AUD-relevant behaviors. Behavioral assays will include a
measure of initiation of acute binge-like drinking and drinking microstructure (Drinking in the Dark), escalation
of drinking in post-dependent animals and negative affective changes in withdrawal (chronic intermittent
alcohol vapor exposure model), and sensitivity to the positive and negative motivational effects of alcohol
(alcohol effects on intracranial self-stimulation). Aim 2 will utilize a complementary translational genetic
approach that seeks to discover genes using a genetically diverse mouse population. Specifically, mice from
the LGxSM Advanced Intercross Line will be tested on a phenotypically-rich model of binge-like alcohol
drinking (Drinking in the dark with lickometers) to characterize consumption, blood alcohol levels, and detailed
characterization of drinking bout structure. The goal of this experiment is to identify novel genes associated
with not only overall consumption, but also specific aspects of the drinking pattern. This aim will provide
significant training in advanced statistical methods for bout analysis and in the quantitative genetics skills
needed for mouse GWAS. Together, the studies proposed here will yield critical biological insights into the
genetics of AUD and excessive drinking.

## Key facts

- **NIH application ID:** 10018802
- **Project number:** 5K99AA027835-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Amanda Malina Barkley-Levenson
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $162,523
- **Award type:** 5
- **Project period:** 2019-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018802

## Citation

> US National Institutes of Health, RePORTER application 10018802, Identification and Characterization of Novel Genetic Mechanisms in Alcohol Use Disorder and Excessive Drinking (5K99AA027835-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10018802. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*