The global aim of the proposed project is to identify and understand the genetic determinants of alcohol dependence, comorbid nicotine dependence, and other drug dependence in African-Americans. To date, the majority of genetic findings related to addiction have come from samples of primarily European descent. With the large volume of data emerging from genome-wide association studies (GWASs) of alcohol dependence and related disorders, replication and validation across populations will play critical roles in solidifying knowledge about genetic determinants of these disorders. Because these emerging GWASs are largely being conducted primarily in samples of European descent, findings from them will need to be validated across populations. Cross-population validation is a key aspect of the gene-discovery process because allele frequencies differ across ethnic groups. In addition, differences in linkage-disequilibrium patterns between African-American and European-American samples can be used to refine genetic signals initially identified in populations of European descent. Hence, this sample would facilitate the important steps of validation and refinement of genetic findings. The project will ascertain 1,000 cases and 1,000 controls matched on gender, age, zip code, and education, from the African-American community. Cases will consist of subjects seeking treatment for alcohol dependence, either alone, or comorbid with other drug dependence;controls will comprise subjects who have consumed alcohol, but are not dependent on alcohol or other substances. Men and women will be equally represented among both cases and controls, so that maximal power to detect gender specific associations is obtained. Thorough assessment of alcohol dependence, comorbid drug dependence, psychiatric disorders, and risk factors will be carried out with widely-used, diagnostic interviews with high reliability and established validity. Genes from published association studies in samples of European or European-American descent, and findings from emerging GWASs in predominantly White samples will be tested for association with alcohol dependence in this African-American sample. Positive findings will be further refined by testing for association with other substance dependence, comorbid psychiatric disorders, and phenotypes related to general addiction liability and externalizing behavior. These analyses will allow determination of whether previous association findings for substance dependence are generalizable to the African-American population, and whether association with other population-specific variants is observed in the candidate gene regions. State-of-the art methods will be used to ensure thorough coverage of candidate gene regions, and genomic control SNPs will be used to test for potential population stratification. In summary, this project would be among the first genetic studies of alcohol dependence to focus specifically on African- Americans, thus addressing a significant public health problem in an under-studied and underserved population.
The economic costs associated with abuse of alcohol have been estimated at $184 billion per year and excessive alcohol use is one of the top contributors to preventable early mortality in the United States today. Though genetic research holds great promise toward the development of individualized treatment and diagnosis for complex disease such as alcohol dependence, there have been comparatively few genetic studies of alcohol dependence that have focused specifically on African-Americans. To help ensure that the benefits of genetic medicine are realized for this population, the current application seeks to develop a sample of African- Americans with and without alcohol dependence, for targeted genetic studies, using findings from samples of European-descent to guide initial genetic analyses.
|Krauss, Melissa J; Cavazos-Rehg, Patricia A; Agrawal, Arpana et al. (2015) Long-term effects of minimum legal drinking age laws on marijuana and other illicit drug use in adulthood. Drug Alcohol Depend 149:173-9|
|Myerson, Joel; Green, Leonard; van den Berk-Clark, Carissa et al. (2015) Male, But Not Female, Alcohol-Dependent African Americans Discount Delayed Gains More Steeply than Propensity-Score Matched Controls. Psychopharmacology (Berl) 232:4493-503|
|Chen, Li-Shiun; Baker, Timothy B; Piper, Megan E et al. (2014) Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction. Drug Alcohol Depend 143:36-43|
|Plunk, Andrew D; Syed-Mohammed, Husham; Cavazos-Rehg, Patricia et al. (2014) Alcohol consumption, heavy drinking, and mortality: rethinking the j-shaped curve. Alcohol Clin Exp Res 38:471-8|
|Glass, Joseph E; Williams, Emily C; Bucholz, Kathleen K (2014) Psychiatric comorbidity and perceived alcohol stigma in a nationally representative sample of individuals with DSM-5 alcohol use disorder. Alcohol Clin Exp Res 38:1697-705|
|Krauss, Melissa J; Cavazos-Rehg, Patricia A; Plunk, Andrew D et al. (2014) Effects of state cigarette excise taxes and smoke-free air policies on state per capita alcohol consumption in the United States, 1980 to 2009. Alcohol Clin Exp Res 38:2630-8|
|Grucza, Richard A; Plunk, Andrew D; Hipp, Pamela R et al. (2013) Long-term effects of laws governing youth access to tobacco. Am J Public Health 103:1493-9|
|Derringer, Jaime; Krueger, Robert F; Dick, Danielle M et al. (2012) The aggregate effect of dopamine genes on dependence symptoms among cocaine users: cross-validation of a candidate system scoring approach. Behav Genet 42:626-35|
|Grucza, Richard A; Hipp, Pamela R; Norberg, Karen E et al. (2012) The legacy of minimum legal drinking age law changes: long-term effects on suicide and homicide deaths among women. Alcohol Clin Exp Res 36:377-84|
|Agrawal, Arpana; Lynskey, Michael T; Hinrichs, Anthony et al. (2011) A genome-wide association study of DSM-IV cannabis dependence. Addict Biol 16:514-8|
Showing the most recent 10 out of 11 publications