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

> **NIH NIH R01** · SUNY DOWNSTATE MEDICAL CENTER · 2024 · $407,498

## Abstract

PROJECT SUMMARY
Known genetic risk factors for Alzheimer’s disease and its related dementias (ADRD), including Apolipoprotein
(APOEε4) and related variants, have been associated with poorer cognitive outcomes and other adverse health
conditions later in life among individuals without Alzheimer’s. Recent studies have also demonstrated early
developmental changes in brain structures and function in healthy young APOEε4 carriers. Studying genetic risk
factors for ADRD beginning in childhood and adolescence may provide the earliest indicators for individuals who
might benefit from interventions or preventive measures for cognitive impairments and other complex health
conditions that manifest across the lifespan. Heavy alcohol use has been shown to negatively impact brain
development and cognitive functioning throughout the lifespan, with new data suggesting that alcohol abuse is
associated with a 4-fold increase in risk for Alzheimer’s and exacerbates the transition from mild cognitive
impairment to dementia. Post-traumatic stress disorder (PTSD), which is highly comorbid with alcohol use
disorder (AUD), is also associated with approximately 2-fold increase in risk for dementia, with research
suggesting the impact of PTSD on risk for dementia varies based on APOEε4 status. Despite the known adverse
effects of chronic alcohol misuse on brain function, and an association between heavy drinking, traumatic stress,
PTSD, and increased risk of dementia, there are few studies that have specifically examined the relationship
between ADRD in this context. In response to NOT-AG-23-032, which requests administrative supplements for
existing NIH grants to develop a new focus on ADRD, the primary aim of this study is to investigate the
association of genomic risk for ADRD (including and excluding APOEε4, given its large effect size) with
longitudinal measures of brain functioning (i.e., neural connectivity), and the moderating influence of alcohol use
behavior and traumatic stress/PTSD. Data will be drawn from the Collaborative Study on the Genetics of
Alcoholism (COGA)’s longitudinal prospective study of adolescents and young adulthood from diverse families
enriched with AUD and traumatic stress (53% female, 28% Black; 8% Hispanic), with detailed assessments of
drinking histories and patterns, diagnostic measures of DSM-5 AUD and PTSD, repeated assessments of brain
functioning and GWAS data. Polygenic risk scores (PRS) will be computed based on summary statistics from a
meta-analysis of 111,326 Alzheimer’s cases and 677,663 unaffected individuals (Bellenguez et al., 2022). Neural
connectivity will be measured with inter- and intra-hemispheric EEG coherence (eyes closed resting state in the
theta (3-7 Hz), alpha (7-12 Hz) and beta (12-28 Hz) frequency bands). Study findings will enhance understanding
of how Alzheimer’s risk factors (genetics, heavy alcohol use, traumatic stress, PTSD, neural development)
typically studied later in life, manifest earlier in the li...

## Key facts

- **NIH application ID:** 10940130
- **Project number:** 3R01AA030010-02S1
- **Recipient organization:** SUNY DOWNSTATE MEDICAL CENTER
- **Principal Investigator:** ANANDA B AMSTADTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $407,498
- **Award type:** 3
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10940130

## Citation

> US National Institutes of Health, RePORTER application 10940130, Genetic relationships between PTSD and Alcohol Use Disorder: Integrating GWAS and Deeply Phenotyped Longitudinal data. (3R01AA030010-02S1). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/10940130. Licensed CC0.

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