# Understanding the role of modifiable lifestyle and psychosocial factors in moderating genetic risk for alcohol use problems in veterans

> **NIH VA IK1** · VA CONNECTICUT HEALTHCARE SYSTEM · 2022 · —

## Abstract

The current Career Development Award-Level 1 (CDA-1) proposal will expand Dr. Peter Na’s
research scope to incorporate psychiatric genetics skills through comprehensive training in
psychiatric genomics, statistical genetics, functional genomics and advanced psychiatric
epidemiology. His mentors are leading experts in the field of psychiatric genetics and psychosocial
epidemiology - Drs. Joel Gelernter, Robert Pietrzak, and Renato Polimanti, with collaboration from Dr.
Hang Zhou, a computational biologist. Dr. Na will also pursue additional training through advanced
workshops, seminars and courses offered by Yale University and other institutions. The proposed
research project will investigate environmental (e.g., trauma load), psychosocial (e.g., purpose in life),
and lifestyle (e.g., physical exercise) (EPL) factors that moderate polygenic susceptibility for alcohol
use disorder (AUD) in Veterans using state-of-the art polygenic risk scores (PRS) computed from the
world’s largest contemporary genome-wide association studies (GWAS) of this disorder. Further, the
proposed study will advance the field’s understanding of the biopsychosocial etiology of AUD and
alcohol consumption using cutting-edge genetic research methodologies such as gene enrichment
and drug-repositioning analyses. While there have been advances in the understanding of genetics of
AUD and psychosocial risk and protective factors for this disorder, the interaction between biological
and EPL factors in predicting AUD remain poorly understood. To address this gap, the proposed
study aims to identify EPL factors that moderate polygenic liability for AUD in Veterans using multiple
large data sets, including the Million Veteran Program (MVP), the National Health and Resilience in
Veterans Study (NHRVS) and the Yale-Penn Study. This line of research directly addresses the top
priority research areas of the Veterans Health Administration (VHA) and this RFA (i.e., substance use
disorders, precision medicine, diseases with a high healthcare burden in Veterans). The moderating
EPL variables identified in the proposed study will elucidate targets for clinical interventions to prevent
and treat AUD in Veterans and ultimately help guide VA clinical practices. PRS will be derived using
the GWAS of AUD from the MVP cohort (N=267,391), of alcohol dependence from the Psychiatric
Genomics Consortium (N=46,568), of the quantity-frequency trait derived from the Alcohol Use
Disorders Identification Test from the UK Biobank (N=121,604), and of alcohol consumption
(drinks/week) from GSCAN (GWAS & Sequencing Consortium of Alcohol and Nicotine use;
N=537,352). Potential moderating EPL factors will be selected based on previous literature. The
associations between PRS, selected EPL factors, and their interaction in predicting AUD and alcohol
consumption will be examined using binomial and multinomial logistic regression analyses. PRS
enrichment analysis will be conducted to examine the biological processes...

## Key facts

- **NIH application ID:** 10485377
- **Project number:** 1IK1CX002532-01
- **Recipient organization:** VA CONNECTICUT HEALTHCARE SYSTEM
- **Principal Investigator:** Peter Na
- **Activity code:** IK1 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485377

## Citation

> US National Institutes of Health, RePORTER application 10485377, Understanding the role of modifiable lifestyle and psychosocial factors in moderating genetic risk for alcohol use problems in veterans (1IK1CX002532-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10485377. Licensed CC0.

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