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

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $569,519

## Abstract

Summary
 Alcohol use disorder (AUD) causes 1 in 20 deaths worldwide and imposes huge economic costs on
society. Twin studies have shown that the risk for developing AUD is heritable. Genome wide association
studies (GWAS) have indicated that, like most psychiatry diseases, AUD is highly polygenic. Although GWAS
in both humans and rodents are powerful techniques, with different strengths and weaknesses, techniques to
integrate the two are poorly developed. GWAS identify individual SNPs that influence a trait; because those
SNPs are species specific, polygenic risk scores (PRS) and similar approaches cannot be used to transfer
information across species. To address this limitation, we are proposing a framework for transferring polygenic
signals across species. We introduce the concept of polygenic transcriptomic risk scores (PTRS). Whereas
PRS sum the effects of many SNPs, a PTRS sums the effects of genetically predicted transcript abundance
across many genes. Because these effects are at the gene, rather than SNP level, they can be applied to
orthologous genes in other species. The extent to which a PTRS for AUD that was developed in humans might
predict rodent behaviors believed to be relevant to AUD is currently unknown. In this grant we will assess
whether PTRS can be used to translate polygenic signals related to AUD between humans and rodents. We
focus on AUD because of the existence of high quality human GWAS data about AUD and related traits like
alcohol consumption. In Aim 1, we will phenotype 1,250 HS rats for multiple alcohol self-administration traits.
In Aim 2, we will perform GWAS and transcriptome wide association analysis (TWAS) for alcohol-related traits
in the rats from Aim 1. In Aim 3, we will build PTRS for AUD and related traits and optimize them for portability
across species. These aims address a critical limitation, namely the inability to transfer polygenic knowledge
between species, which is inhibiting progress towards a deeper understanding of how polygenic liability for
AUD alters molecular and cellular processes, brain circuits and behaviors. If successful, our results will open
new avenues for research aimed at prediction, prevention, and treatment of AUD.

## Key facts

- **NIH application ID:** 10340683
- **Project number:** 1R01AA029688-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Hae Kyung Im
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $569,519
- **Award type:** 1
- **Project period:** 2022-09-16 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10340683

## Citation

> US National Institutes of Health, RePORTER application 10340683, A Framework for Translating Polygenic Findings Related to Alcohol Use Disorder Across Species (1R01AA029688-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10340683. Licensed CC0.

---

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