Defining Alcohol-Related Phenotypes in Humans: The Collaborative Study on the Genetics of Alcoholism

Article excerpt

The Collaborative Study on the Genetics of Alcoholism (COGA) is an innovative, large-scale, multidisciplinary research program launched by the National Institute on Alcohol Abuse and Alcoholism to investigate the genetic components that contribute to the development of alcohol abuse and dependence. The study--which involves 9 research centers located across the United States--relies primarily on DNA samples, questionnaires, electrophysiological measurements, and other data obtained from nearly 3,000 people from families with at least 3 alcoholic members. Dr. Laura Jean Bierut and her colleagues describe the genetic analyses conducted on these DNA samples in an effort to identify DNA regions (i.e., loci) that carry genes influencing the risk of alcoholism and other alcohol-related traits. Although focusing on the methodology of the COGA study, the authors also summarize some key findings regarding loci on chromosomes 1 and 4 that influence such traits as alcohol dependence, level of response to alcohol, presence of alcoholism or depression, or maximum number of drinks a person may consume in one sitting. (pp. 208-213)

Alcoholism is a disease that runs in families and results at least in part from genetic risk factors. The Collaborative Study on the Genetics of Alcoholism (COGA) is a Federally funded effort to identify and characterize those genetic factors. The study involves more than 1,000 alcoholic subjects and their ramifies, with researchers conducting comprehensive psychological, physiological, electrophysiological, and genetic analyses of the participants. These analyses have identified several traits, or phenotypes, that appear to be genetically determined, such as the presence of alcohol dependence, the level of response to alcohol, the presence of coexisting depression, or the maximum number of drinks a person consumes per occasion. Genetic analyses have identified regions on several chromosomes that are associated with these phenotypes and need to be studied further. KEY WORDS: genetic theory of AODU (alcohol and other drug use); AODR (alcohol and other drug related) genetic markers; phenotype; chromosome; AOD dependence potential; genetic variance; genetic trait; comorbidity; major depression; AOD intake per occasion; electroencephalography; genetic linkage; genetic correlation analysis

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Alcohol dependence is a common, complex disorder that clusters in families. Strong evidence from twin and adoption studies suggests that alcoholism is in part caused by a genetic predisposition. (Definitions of the terms "alcoholism" or "alcohol dependence" are discussed later in this article.) Many other traits that are associated with the risk for alcoholism also cluster in families and have genetic underpinnings. These traits, or phenotypes, include a person's response to alcohol; the maximum amount of alcohol a person consumes on a single occasion; and biological measurements, such as brain electrophysiological measures. Certain psychiatric disorders that commonly co-occur with and may increase the risk for alcoholism, such as depression, antisocial personality disorder, or abuse of other drugs, also may be caused partly by genetic factors. Genetic studies of complex disorders can use analyses of such correlated characteristics to improve the likelihood of finding genes that are associated with the development of these disorders. To use this strategy, researchers must conduct comprehensive assessments in multiple domains (e.g., behavioral responses and physiological reactions). This approach allows for the examination of multiple characteristics that may be influenced by the same underlying genes.

The Collaborative Study on the Genetics of Alcoholism (COGA) is an ambitious research effort funded by the National Institute on Alcohol Abuse and Alcoholism to elucidate the genetic factors contributing to the risk of alcoholism. …

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