Prevalent alcohol dependence (AD) in the United States, which has increased substantially over the past decade, is highly destructive and costly to individuals and to society. It is also moderately heritable. Delirium tremens (DTs) is a frequent, and often dangerous, consequence of acute alcohol withdrawal. We previously conducted an AD research project focused on the understudied African-American (AA) population and carried out numerous investigations including a pioneering genomewide association study (GWAS) of AD. We also reported GWAS of numerous related traits. Our findings included genomewide significant (GWS) risk loci associated to AD and related traits; our preliminary data support a risk locus for DTs at UNC13C (P= 9.410[-9]). Many significant findings, including the DT association, are seen exclusively in AAs. Additional recruitment of AA AD subjects with a state-of-the-art assessment is necessary. Deep phenotyping will make available other relevant related phenotypes, such as risky sexual behavior. New recruitment will build upon our existing sample to increase gene-mapping power not just for AD, but also for other substance use disorder (SUD) traits that are highly comorbid with AD in clinical populations. This resource will enable replication and a more detailed and broader investigation of identified associations. The focus on AA subjects will (a) help to address the well-recognized disparity in complex trait studies of this population; (b) allow us to follow-up GWAS results in the specific population where most of our significant results have been observed (pending future funding); and (c) increase power through greater homogeneity of the study sample. Our new subjects (pending future projects to allow genotyping and analysis based on the subjects to be collected here) will be added to the Psychiatric Genomics Consortium sample to improve the power of their SUD mega-analyses.

Public Health Relevance

Alcohol dependence is highly destructive to individuals and society in the United States and throughout the world; and delirium tremens (DTs) is a common dangerous medical outcome of acute alcohol withdrawal. Variation in genes influences the risk for alcohol dependence and DTs. The main objective of this study is to enable future work that will find genes that influence risk for alcohol dependence and DTs in this mostly-African Ancestry sample

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA026364-03
Application #
9994806
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Parsian, Abbas
Project Start
2018-09-01
Project End
2023-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
3
Fiscal Year
2020
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