# Overlap in genetic and learning-based mechanisms for alcohol use disorder and posttraumatic stress disorder

> **NIH NIH K01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $167,828

## Abstract

Project Summary
 Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are common outcomes following
trauma that are frequently comorbid, and this comorbidity is associated with greater symptom severity and
poorer prognosis. Thus, efforts to better understand the etiology of these conditions is important for decreasing
negative outcomes and improving prevention and treatment efforts, as much is still unknown regarding the
etiology and mechanisms involved in their co-occurrence. Recent research has found that in addition to both
phenotypes being moderately heritable, there is a modest degree of overlap in their latent genetic risk.
Moreover, there is reason to suggest that fear-learning mechanisms frequently associated with PTSD may also
be associated with AUD. Areas in need of further research include identification of molecular variation
responsible for AUD/PTSD comorbidity, and extension of fear-learning models to AUD and comorbid
AUD/PTSD populations. Developments in statistical procedures have afforded the ability to leverage genome-
wide association data to answer key questions about these shared molecular underpinnings. The overarching
goals of this K01 proposal are threefold. First, the study aims to use existing large-scale genome-wide data
from the Psychiatric Genomics Consortium (PGC; PTSD and Substance Use Disorders workgroups) to
examine the molecular overlap via bivariate single nucleotide polymorphism (SNP)-based heritability models,
and determine if the polygenic risk score (PRS) from each disorder predicts case status in the other dataset.
Second, a clinical laboratory study will be conducted using fear-conditioning paradigms in a trauma-exposed
sample of diagnosis free controls, AUD, PTSD, and comorbid AUD/PTSD diagnostic groups to determine if
deficits in learning are shared. Finally, an exploratory aim will use the PRS scores from the PGC data to
generate risk scores in the lab sample to examine if there is a genetic association with conditioning deficits.
 To achieve these aims, the candidate and multidisciplinary mentorship team have developed a
comprehensive training plan that delineates a series of training and research goals. These goals will
incorporate training in the epidemiology and genetics of AUD and PTSD, molecular and statistical genetics
techniques, and conduct of clinical laboratory paradigms using genetic and psychophysiological measures.
This training and resultant findings will capitalize on existing expertise and provide additional, focused training
to allow for the development of a multimodal research program that uses large-scale genetic association
findings to develop mechanism-focused laboratory studies that inform upon the development and maintenance
of this complex presentation. The proposed research represents an important contribution towards advancing
our understanding of the complicated and frequently comorbid phenotypes of AUD and PTSD. The institutional
environment is ideal for the c...

## Key facts

- **NIH application ID:** 9920643
- **Project number:** 5K01AA025692-03
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Christina M Sheerin-Smith
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $167,828
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920643

## Citation

> US National Institutes of Health, RePORTER application 9920643, Overlap in genetic and learning-based mechanisms for alcohol use disorder and posttraumatic stress disorder (5K01AA025692-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9920643. Licensed CC0.

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