The main goal of the Collaborative Study on the Genetics of Alcoholism (COGA) is to localize, identify and characterize genes influencing alcohol dependence and related phenotypes. A primary focus is to continue to identify genes in which variants affect the risk for alcoholism and related disorders. This includes identifying additional genes in adults, including testing the results from other studies and from joint analyses of multiple studies. Related to this is the characterization of the molecular and cellular mechanisms through which the variants act. Another major focus is the study of adolescents and young adults, to examine genetic effects across development and to understand the environmental factors that affect expression of genetic risk in this critical age range. This will be carried out through a prospective study in which participants are carefully assessed for many behavioral and neural phenotypes. An important part of this is the development of novel behavioral and neurophysiological phenotypes related to risk for alcoholism and to brain functions, which can help both in identifying relevant genes and understanding the mechanisms through which they work. We will test the hypothesis that genes affecting risk for alcoholism and related phenotypes in adults also affect related phenotypes in adolescents. We will also test the hypothesis that exposure to alcohol during key developmental stages causes epigenetic modifications that alter gene expression thereby affecting the long-term risk for alcoholism and its sequelae. Supporting these efforts will be the maintenance of high quality databases and biological materials, and making these available to approved external investigators. Together these aims go from identifying genes in which variants affect risk for alcoholism to understanding how they act at multiple levels, from molecular and cellular to behavioral, neurophysiological and phenotypic levels as a function of development. We anticipate that through the delineation of the pathways and genes contributing to alcohol dependence and alcohol use and abuse, we will directly impact the ability to successfully treat alcohol problems and intervene in those at greatest risk.

Public Health Relevance

Alcoholism is a major social and health problem. It has been estimated that misuse of alcohol costs the US over $180 billion per year, and that alcohol is the third leading cause of loss of disability adjusted life years in Western countries. Understanding how genetic variations affect the risk for alcoholism will make important contributions to prevention and treatment of this serious disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10AA008401-22
Application #
7944055
Study Section
Special Emphasis Panel (ZAA1-CC (10))
Program Officer
Noronha, Antonio
Project Start
1989-09-29
Project End
2014-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
22
Fiscal Year
2010
Total Cost
$6,890,683
Indirect Cost
Name
Suny Downstate Medical Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
040796328
City
Brooklyn
State
NY
Country
United States
Zip Code
11203
Smit, Dirk J A; Wright, Margaret J; Meyers, Jacquelyn L et al. (2018) Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity. Hum Brain Mapp 39:4183-4195
Cabana-Domínguez, Judit; Arenas, Concepció; Cormand, Bru et al. (2018) MiR-9, miR-153 and miR-124 are down-regulated by acute exposure to cocaine in a dopaminergic cell model and may contribute to cocaine dependence. Transl Psychiatry 8:173
Su, Jinni; Kuo, Sally I-Chun; Aliev, Fazil et al. (2018) Influence of Parental Alcohol Dependence Symptoms and Parenting on Adolescent Risky Drinking and Conduct Problems: A Family Systems Perspective. Alcohol Clin Exp Res 42:1783-1794
Miller, M L; Ren, Y; Szutorisz, H et al. (2018) Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability. Mol Psychiatry 23:1328-1335
Olfson, Emily; Bloom, Joseph; Bertelsen, Sarah et al. (2018) CYP2A6 metabolism in the development of smoking behaviors in young adults. Addict Biol 23:437-447
Salvatore, Jessica E; Dick, Danielle M (2018) Genetic influences on conduct disorder. Neurosci Biobehav Rev 91:91-101
Edenberg, Howard J; McClintick, Jeanette N (2018) Alcohol Dehydrogenases, Aldehyde Dehydrogenases, and Alcohol Use Disorders: A Critical Review. Alcohol Clin Exp Res 42:2281-2297
Edwards, Alexis C; Deak, Joseph D; Gizer, Ian R et al. (2018) Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity. Alcohol Clin Exp Res 42:2349-2359
Korhonen, Tellervo; Sihvola, Elina; Latvala, Antti et al. (2018) Early-onset tobacco use and suicide-related behavior - A prospective study from adolescence to young adulthood. Addict Behav 79:32-38
Wang, Kesheng; Chen, Xue; Ward, Stephen C et al. (2018) CYP2A6 is associated with obesity: studies in human samples and a high fat diet mouse model. Int J Obes (Lond) :

Showing the most recent 10 out of 466 publications