# A Framework for Translating Polygenic Findings Related to Alcohol Use Disorder Across Species

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $382,829

## Abstract

Summary/Abstract for the Supplement
 We are requesting a supplement to our NIAAA R01 (R01AA029688) entitled “A Framework for
Translating Polygenic Findings Related to Alcohol Use Disorder Across Species”. This supplement request is
in response to NOT-AG-23-032. The start date of the parent grant is September 16, 2022, and the end date is
August 31, 2027. Consistent with NOT-AG-23-032, our proposal will “examine the fundamental mechanism
underlying alcohol effects on the vulnerability to the cognitive impairments associated with dementias”.
 There is a well established link between alcohol consumption and Alzheimer’s disease (AD). In
particular, heavy drinking increases the risk for developing AD. One possible explanation is that alcohol
exposure drives this correlation, but another possibility is that the genetic risk for alcohol consumption and/or
alcohol use disorder (AUD) contributes to the risk for developing AD due to the genetic risk for high alcohol
consumption or AUD, even in the absence of exposure to alcohol. These issues are difficult or impossible to
disentangle in humans because their exposure to both alcohol and other known and unknown environmental
exposures relevant to AD is governed by both direct and indirect genetic effects as well as complicated genetic
population structure which is itself correlated with environmental exposures that may influence both AD and
AUD. Therefore, an experimental system is needed. However, currently available AD animal models tend to
focus on a few highly penetrant alleles, which are not the primary drivers of human AD, and thus do not model
the highly polygenic AD risk that is responsible for the majority of the disease burden.
 We are proposing to address this important knowledge gap by using a sophisticated statistical genetic
approach. We will use the polygenic transcriptomic risk score (PTRS) method, which is the focus of the parent
grant, to predict the “Rat Alzheimer’s Disease Associated Risk” (RADAR) score for all 1,250 HS rats being
phenotyped in the parent grant. We will examine correlations between RADAR scores and the measures of
alcohol dependence, withdrawal and sensitivity being collected in the parent grant. This will allow us to assess
the genetic relationship between AD and behavioral measures relevant to AUD in an experimental system that
does not suffer from the many confounds that limit the interpretations of human genetic data on the relationship
between AD and AUD.

## Key facts

- **NIH application ID:** 10940436
- **Project number:** 3R01AA029688-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Hae Kyung Im
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $382,829
- **Award type:** 3
- **Project period:** 2022-09-16 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10940436

## Citation

> US National Institutes of Health, RePORTER application 10940436, A Framework for Translating Polygenic Findings Related to Alcohol Use Disorder Across Species (3R01AA029688-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10940436. Licensed CC0.

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