# The Heritable Transcriptome and Alcoholism

> **NIH NIH R24** · UNIVERSITY OF COLORADO DENVER · 2020 · $663,125

## Abstract

The goal of this application is to establish an animal model and accompanying database suitable for a systems
genetic analysis of complex traits, specifically traits that represent genetic predisposing factors for alcohol use
disorder (AUD). Systems genetic approaches require a global analysis of factors such as gene expression,
protein and metabolite levels in multiple tissues of an organism, as well as an understanding of gene-gene and
gene-environment interactions, and the interdependency of these factors in contributing to complex
traits/disorders. As a result, a key requirement for an animal model is a genetically stable population that can
be studied repeatedly, over many generations, to provide cumulative data that can eventually allow for a
complete systems genetic analysis. During the past grant periods, we have progressed well with the
development of a Hybrid Rat Diversity Panel (HRDP) that meets these criteria. We have chosen to focus on
the rat, rather than the mouse, for studies of complex traits related to AUD, because of the greater size of the
rat brain, the ease of training in operant tasks, and the rat’s higher cognitive ability. We have generated DNA
sequence data, RNA sequence data and whole genome exon array data on four tissues (brain, liver [whole
organ and cell-specific data], heart and brown adipose tissue) from rat strains of the HXB/BXH recombinant
inbred (RI) panel and from classic inbred rat strains. We have mapped QTLs for behavioral/physiological traits
(alcohol consumption, alcohol deprivation effect, alcohol metabolism including acetate levels after alcohol
administration), as well as used transcriptome data to map expression QTLs, to generate transcript
coexpression modules and map module eigengene (first principal component) QTLs. These data have been
used to identify candidate genes and transcriptional networks that contribute to the measured biochemistry and
behaviors. All of our raw, processed and analyzed data have been made available to the research community
on our PhenoGen website (http://phenogen.ucdenver.edu). This website, that we developed, also includes
several visualization tools to explore these data in a systems genetics framework and allows the user to
observe genetic relationships between a complex phenotype of interest and networks of gene products that
influence the phenotype. We are now proposing to complete the main core of transcriptional data for the 96-
strain HRDP, adding data from another rat RI panel (FXLE/LEXF) and more inbred rat strains. We will obtain
full transcriptome information of brain and liver of male and female rats from all strains, quantify the expression
of transcript isoforms, including 3’UTR isoforms, and analyze the 3’UTR regions for alternative use of
polyadenylation sites and miRNA binding sites. We will use our established and newly developed pipelines to
disseminate integrated, systems level data (PhenoGen and Rat Genome Database). We will also expand our
demonstr...

## Key facts

- **NIH application ID:** 9990635
- **Project number:** 5R24AA013162-19
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Paula Hoffman
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $663,125
- **Award type:** 5
- **Project period:** 2017-08-05 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990635

## Citation

> US National Institutes of Health, RePORTER application 9990635, The Heritable Transcriptome and Alcoholism (5R24AA013162-19). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9990635. Licensed CC0.

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