# Genetic relationships between PTSD and Alcohol Use Disorder: Integrating GWAS and Deeply Phenotyped Longitudinal data.

> **NIH NIH R01** · SUNY DOWNSTATE MEDICAL CENTER · 2022 · $555,217

## Abstract

Project Summary/Abstract
 Childhood trauma exposure, particularly in the form of interpersonal violence, increases risk for alcohol
use disorder (AUD), posttraumatic stress disorder (PTSD) and their co-occurrence throughout the lifespan. AUD
and PTSD frequently co-occur, and comorbidity is associated with a host of negative clinical outcomes, including
greater symptom severity, poorer treatment prognosis, suicidal ideation, and poor physical health. Mechanisms
of comorbidity remain largely unknown, but shared risk in the form of overlapping genetic etiology may play a
role. AUD and PTSD are moderately heritable, overlap in latent genetic risk, and are genetically correlated in
large GWAS studies (rG=0.35), particularly among women. In addition to genetic risk, trauma exposure may be
a shared risk factor for adult AUD and PTSD, the impact of which may be exacerbated by genetic risk. However,
the mechanisms by which trauma increases risk need to be identified. Preliminary evidence suggests that
childhood trauma impacts brain development (i.e., atypical EEG activity observed during adolescence and young
adulthood), which in turn increases risk for AUD and PTSD. Effects were more robust among females and those
with a family history of AUD. Despite these promising findings, little is known about the influence of trauma on
adolescent and young adult brain development and risk for AUD and PTSD, and no other studies have examined
these factors together in a longitudinal paradigm, leaving the complex interactions among childhood trauma,
polygenic, and neurodevelopmental risk for AUD and PTSD poorly understood. The present study will fill these
gaps in the literature in a highly translational set of aims. Building of the research team’s prior work, this study
will assess the impact of childhood trauma on longitudinal trajectories of brain functioning (i.e., EEG functional
connectivity) and risk for adult AUD and PTSD using data from the Collaborative Study on the Genetics of
Alcoholism’s prospective study. Next, using summary statistics from the largest genome wide association studies
(GWAS) on AUD, AUD-related phenotypes (e.g., alcohol use behaviors) and PTSD, we will elucidate the genetic
factor structure of these phenotypes. A novel multivariate genetic method, genomic Structural Equation Modeling
(gSEM), will be used to determine the factor structure, and the resulting best-fit model will be used to produce
polygenic risk scores (PRS) that index shared genetic risk between the phenotypes (e.g., AUD-PTSD), as well
as unique risk for each condition. Finally, these PRS indexing risk unique and common for AUD-PTSD will be
integrated into the longitudinal analyses of childhood trauma, EEG functional connectivity, and risk for adult AUD
and PTSD. Important sex differences will also be examined. Results from this study will shed light on these
important public health conditions and will yield important implications for prevention and intervention efforts.

## Key facts

- **NIH application ID:** 10418931
- **Project number:** 1R01AA030010-01
- **Recipient organization:** SUNY DOWNSTATE MEDICAL CENTER
- **Principal Investigator:** ANANDA B AMSTADTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $555,217
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418931

## Citation

> US National Institutes of Health, RePORTER application 10418931, Genetic relationships between PTSD and Alcohol Use Disorder: Integrating GWAS and Deeply Phenotyped Longitudinal data. (1R01AA030010-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10418931. Licensed CC0.

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