# Characterizing the sex-specific genetic architecture of alcohol use disorders with comorbid major depressive disorder

> **NIH NIH K01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $164,349

## Abstract

PROJECT SUMMARY/ABSTRACT
 Lifetime Alcohol Use Disorder (AUD) has an estimated US lifetime prevalence of 29.1%.
Major Depressive Disorder (MDD) is often comorbid with AUD, with an estimated lifetime AUD
prevalence of 40.8% among those with lifetime MDD. This comorbidity was unequally
distributed by sex globally, with prevalence nearly twice as high in men as in women. AUD and
MDD are moderately heritable, with and a substantial proportion of the underlying genetic
liability between AUD and MDD is shared, (rg = 0.56). The temporal order of the disorders is
complex and likely differs by sex. This project proposes to leverage data from 10 existing
collections from longitudinal, diverse ancestry cohorts to analyze the interacting sex, genetic,
and co-morbid MDD effects on the trajectory of AUD. These analyses represent modeling
approaches not previously applied in these datasets and successful completion of the proposed
research will elucidate biological mechanisms of alcohol etiology by investigating sex-specific
and time-varying genetic influences on item-level measures of AUD. Importantly, this proposal
also includes development of novel machine learning (ML) approaches for predicting missing
and/or unmeasured AUD outcomes from existing, biobank-scale data to improve power for
genetic analyses.
 This K award will provide the structured training and mentorship in molecular genetics
for complex traits and ancestrally diverse samples as well as psychiatric nosology and
epidemiology necessary for the candidate to develop the expertise needed to support her goal
of becoming an independent and innovative researcher in alcohol epidemiology. Combined with
her background in biostatistics and analytical methods, the proposed training and research
activities will develop her capacity posit the kinds of research hypothesis, comprehensive plans,
and wholistic, innovative approaches which are most relevant to advancing science and
medicine in alcohol research. In sum, with dedicated mentoring, the planned training and
research will equip the candidate to establish a strong line of competitive research supporting a
long-term goal of an independent research plan that integrates novel statistical and
computational approaches to elucidate the genetic and environmental factors and interactions
contributing to AUD.

## Key facts

- **NIH application ID:** 10949853
- **Project number:** 1K01AA031748-01
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Amanda Elswick Gentry
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $164,349
- **Award type:** 1
- **Project period:** 2024-09-01 → 2025-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10949853

## Citation

> US National Institutes of Health, RePORTER application 10949853, Characterizing the sex-specific genetic architecture of alcohol use disorders with comorbid major depressive disorder (1K01AA031748-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10949853. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*