# Sex differences in Opioid Dependence: Role of the X-Chromosome

> **NIH NIH R03** · YALE UNIVERSITY · 2020 · $65,450

## Abstract

PROJECT SUMMARY/ABSTRACT
The U.S. is experiencing a crisis on opioid use with escalating numbers of opioid overdose deaths in recent
years. Sex differences exist in multiple phases of opioid dependence (OD) including acquisition, escalation,
addiction, withdrawal, relapse, and treatment response. Overall, men are more likely to become dependent
than women, although women tend to progress and develop medical or social consequences faster, have more
difficulty discontinuing use, and are more vulnerable to relapse. However, the biological and genetic factors for
these differences are poorly understood and have been understudied. We will capitalize on our existing large-
scale genome-wide association study (GWAS) data, which were derived from our substance dependence (SD)
cohort (N>10,000), including African and European American males and females. This SD cohort has been
evaluated by the comprehensive instrument: Semi-Structured Assessment of Drug Dependence and
Alcoholism (SSADDA). Here we propose to analyze the X-chromosome using the genetic data for this SD
cohort. The X-chromosome data have already been collected, but have not been included in our published
GWAS due to technological challenges. As advancement in biotechnology and analytical development, we are
now able to analyze the X-chromosome data. We aim to identify sex-specific risk variants, and test association
between OD and X-linked genetic variants for sex-specific OD patients, to characterize molecular pathways
and genetic functionality, and to dissect genetic architecture between OD men and OD women. Through this
study we will gain the knowledge to identify X-linked genetic variants that may assist in developing treatment
strategies uniquely for men and women OD individuals to be applied in clinical treatment as remedies for the
opioid crisis in the US. By completion of this study our research will aid in addressing the objectives in the
three goals of the NIH strategic plan for women's health research: We will contribute to increasing sex
differences research in basic science studies, incorporate sex-specific findings in our design, and contribute to
sex-specific genetic profiling in personalized prevention, diagnostics and potentially treatment strategy for OD
men and women.

## Key facts

- **NIH application ID:** 9889917
- **Project number:** 5R03DA047562-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** BAO-ZHU YANG
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,450
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889917

## Citation

> US National Institutes of Health, RePORTER application 9889917, Sex differences in Opioid Dependence: Role of the X-Chromosome (5R03DA047562-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9889917. Licensed CC0.

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