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 OD than women, although women tend to progress and develop medical or social consequences faster, have more difficulty discontinuing use, and more vulnerable to relapse. Thus, determining sex-specific factors underlying OD is critical for optimizing prevention and treatment strategies for men and women with OD. Identifying relevant genetic factors holds particular promise. Although studies have reported sex-specific heritability of OD and different association results for men and women for some candidate genes in OD, the results to date are meagre, and sex-specific genome wide association studies (GWAS) on OD have never been reported. We will use rigorous statistical approaches to identify sex-specific genetic risk factors for OD. We have a well-characterized substance-dependent (SD) cohort for African and European Americans with GWAS and exome-array data that can be analyzed and leveraged with publically available genetic and genomics data. This large SD cohort has been assessed using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) instrument. In this proposal, OD defined by DSM criterion count will be the targeted trait for analysis. The overall goal of this administrative supplement proposal is to analyze the genetic data we have collected for women and men to identify most effectively sex-specific genetic variants.

Public Health Relevance

The objective of this project is to discover sex-specific genetic risk variants of opioid dependence for males and females. This project has the capacity to advance our understanding of the differing and similar genetic mechanisms of opioid dependence for women and men, with the resulting information helping to optimize sex-specific prevention and treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA012690-15S1
Application #
9432193
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Pollock, Jonathan D
Project Start
2000-08-05
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2019-08-31
Support Year
15
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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