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Genome scans and maximum number of drinks consumed in 24 hours indicate alcoholism hotspot on chromosome 4
Edward R. Winstead

Researchers used an innovative gene-hunting strategy to identify a chromosome region that may contain susceptibility genes for alcoholism. The researchers found the region by analyzing two sets of data: scans of an individual's genome and a statistic reported by the individual—the maximum number of drinks he or she consumed in a 24-hour period ('M'). The region of chromosome 4 implicated in the study was already suspected in the disease; it contains alcohol dehydrogenases (ADH) genes, which play a role in alcohol metabolism and tolerance.

Researchers at Washington University in St. Louis developed the strategy to identify chromosome regions containing genes that contribute modestly to the development of alcoholism. Alcoholism is likely to involve many genes, and finding 'disease' genes of small effect is rarely easy. The researchers decided instead to investigate a trait that is essentially a component of a greater genetic entity.

Studies of twins have demonstrated that the maximum-number-of-drinks statistic, designated M by the researchers, has a genetic component. And despite the fact that the event is a one-time occurrence, M is an indicator of alcoholism. Furthermore, M differs significantly between alcohol dependent subjects with and without a psychological component, according to the researchers.

"It is perhaps unexpected, but instructive, to find that a simple measure based on a single self-reported interview item appears to capture important information relating to diagnosis," Nancy L. Saccone, of Washington University, St. Louis, and colleagues write in a paper describing the research. The paper appeared in a recent issue of the American Journal of Medical Genetics.

Families in the study were recruited by the Collaborative Study on the Genetics of Alcoholism (COGA), a consortium of researchers at six US universities founded in 1989. COGA has extensive clinical, neuropsychological, and genetic data on thousands of individuals, including alcoholics, family members, and a population of unaffected controls. Researchers at the University of Indiana and the State University of New York, Brooklyn, contributed to the current study.

Surveys used by COGA include the question: "What is the maximum number of drinks you have ever had in a 24-hour period?" No other diagnostic, grouped or individual items from the survey were analyzed. The genome scans included a total of 351 genetic markers. The analysis involved a comparison of two distinct groups of COGA families, including both male and female subjects.

The highest report of M was 336. The researchers confirmed that this was the subject's response and not an error of data entry. "It is likely that the extremely high values, given by self-report, are inflated," the researchers write in their paper. They note, however, that the study method is designed to minimize the inflation's impact on the regression analysis.

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Saccone, N.L. et al. A genome screen of maximum number of drinks as an alcoholism phenotype. Am J Med Genet (Neuropsychiatr Genet) 96, 632-637 (October 9, 2000).

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