# Understanding the role of modifiable environmental and psychosocial factors in moderating genetic risk for substance use disorders in Veterans

> **NIH VA IK2** · VA CONNECTICUT HEALTHCARE SYSTEM · 2024 · —

## Abstract

The current Career Development Award-Level 2 (CDA-2) proposal will further advance Dr. Peter Na’s
research scope in psychiatric genetics through comprehensive training in psychiatric genomics,
statistical genetics, epigenetics, functional genomics and advanced psychiatric epidemiology. His
mentors are leading experts in the field of psychiatric genetics and psychosocial epidemiology - Drs.
Joel Gelernter and Robert Pietrzak. 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., adverse childhood experiences), and
psychosocial (e.g., purpose in life, social support) (EP) factors that moderate polygenic susceptibility
for substance use disorders (SUDs) in Veterans using state-of-the art polygenic risk scores (PRS)
computed from large contemporary genome-wide association studies (GWAS) of SUDs. Further, the
proposed study will advance the field’s understanding of the biopsychosocial etiology of SUDs using
cutting-edge genetic research methodologies such as epigenetic, gene enrichment and drug-
repositioning analyses. While there have been advances in the understanding of genetics of SUDs
and EP risk and protective factors for this disorder, the interaction between biological and EP factors
in predicting SUDs remain poorly understood. To address this gap, the proposed study aims to
identify EP factors that moderate polygenic liability for SUDs in Veterans using multiple large data
sets, including the Million Veteran Program (MVP), National Health and Resilience in Veterans Study
(NHRVS) and 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., SUDs, precision medicine,
diseases with a high healthcare burden in Veterans). The moderating EP variables identified in the
proposed study will elucidate targets for clinical interventions to prevent and treat SUDs in Veterans
and ultimately help guide VA clinical practices. PRS will be derived using the GWAS of SUDs from
the MVP cohort. Potential moderating EP factors will be selected based on previous literature. The
associations between PRS, selected EP factors, and their interaction in predicting SUDs will be
examined using machine learning analyses. PRS enrichment analysis will be conducted to examine
the biological processes affected by the interaction. Further, drug repositioning analysis will be
performed to examine the biological mechanisms and identify candidate medications for SUDs that
may be further tested in animal and pilot studies. In addition, epigenetic analyses using longitudinal
data will help identify longitudinal genome-wide DNA methylation differences associated with alcohol
use phenotypes in Veterans. Upon successful completion of the proposed training and research
project, Dr. Na will acquire sufficient expertise and preliminary dat...

## Key facts

- **NIH application ID:** 10924103
- **Project number:** 1IK2CX002817-01
- **Recipient organization:** VA CONNECTICUT HEALTHCARE SYSTEM
- **Principal Investigator:** Peter Na
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924103

## Citation

> US National Institutes of Health, RePORTER application 10924103, Understanding the role of modifiable environmental and psychosocial factors in moderating genetic risk for substance use disorders in Veterans (1IK2CX002817-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10924103. Licensed CC0.

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