# Using a Genetic Approach to Understand Factors Influencing Resistance to Substance Use

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $548,431

## Abstract

PROJECT SUMMARY
The goal of this project is to index individual resistance to psychoactive substance use (SU) during
adolescence and use the indices to identify factors influencing resistance into early middle adulthood (30-40
years old), with a special focus on potentially modifiable factors. One possible cause for the limited success in
reducing SU is a focus on factors that elevate risk for rather than resistance to SU. Although the risk and
resistance aspects of liability to a disorder are symmetric, the respective factors are not. Factors enhancing
resistance may more readily translate into prevention and treatment strategies. In addition, “environmental”
variables, which are more likely to be modifiable than the genetic ones, may be confounded by the genetic
influences. Failure to account for this confounding could hinder the detection of resistance factors. We address
these limitations by measuring liability to SU/SUD in childhood/adolescence using previously collected and
harmonizable data from the Virginia Twin Study of Adolescent and Behavioral Development (VTSABD; 1,214
twin pairs) and Minnesota Twin and Family Study (1,382 twin pairs), and assessing potential resistance
factors. Long-term SU phenotype will be verified in a new wave of VTSABD data collection, where participants
will be 30-50 years old. Aim 1. Develop continuous indices of resistance to SU and estimate genetic and
environmental contributions to their variation. Two indices of SU resistance will be derived using a validated
measure of childhood SU liability (Transmissible Liability Index) and SUD diagnosis in the same individuals as
adults (verified in new Wave 7 SU data) to select psychological items measured in earlier waves. Two
resistance indices will be generated via item response theory analysis: High Outset Resistance (based on
items differentiating between low and average childhood SU liability) and High Realized Resistance (based on
items distinguishing high and average childhood SU liability). Aim 2. Identify novel factors that have the
highest probability of enhancing resistance to substance use. These factors will be sourced as most impactful
on decisions related to substance use, using a Concept Mapping approach and existing data. Aim 3. Evaluate
developmental trajectories of the resistance indices and SU outcomes while determining how these trajectories
vary across levels of resistance factors. This will detail the influence of childhood/adolescent resistance on SU
across the life course. This project will produce detail on potentially modifiable factors that can be targeted to
reduce the likelihood of SU and addiction.

## Key facts

- **NIH application ID:** 10873163
- **Project number:** 5R01DA054313-03
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** HERMINE H MAES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $548,431
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873163

## Citation

> US National Institutes of Health, RePORTER application 10873163, Using a Genetic Approach to Understand Factors Influencing Resistance to Substance Use (5R01DA054313-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10873163. Licensed CC0.

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