Previous family-based research had linked a broad region on chromosome 4q with alcohol dependence (AD). A new study has found that nine of the single nucleotide polymorphisms (SNPs) -- DNA sequence variations -- in the 3' region of the tachykinin receptor 3 gene (TACR3), located within chromosome 4q, have a significant association with AD, particularly those with more severe AD, and co-existing cocaine dependence.
"We believe it is important to identify genes contributing to AD for two primary reasons," said Tatiana M. Foroud, director of the division of hereditary genomics at the Indiana University School of Medicine and first author of the study.
"First, better treatments can be developed which would improve the success rate for those wishing to end their AD," she said. "Second, being able to identify those at greater risk for AD at a young age would allow interventions to be initiated earlier, potentially reducing the likelihood that the individual will become AD."
"The past few years have been an incredibly exciting time in gene identification," added Danielle Dick, assistant professor of psychiatry, psychology, and human and molecular genetics at Virginia Commonwealth University.
"Scientists are now entering an era where genes are being associated with AD and, importantly, these findings are replicating across samples," she said. "We know that AD shows a lot of variability, with affected individuals differing on many dimensions, such as age of onset, severity of symptoms and other co-occurring psychiatric and drug problems. This study makes an effort to understand how the TACR3 gene might contribute to some of this variability, rather than simply treating all AD as the same."
This study is part of the larger Collaborative Study on the Genetics of Alcoholism (COGA), said Foroud, which had previously detected a link between AD and a region on chromosome 4q. "We believe it is likely that multiple genes contributing to AD lie within this chromosomal region," she said. "Given that several lines of evidence suggested that TACR3 was a good candidate gene, we decided to not only test for an association with AD, but also expand our analyses to include additional phenotypes, such as cocaine dependence."
Using COGA data, researchers searched for an association between AD and 30 SNPs throughout TACR3 among 219 European American families (n=1,923 genotyped individuals). Researchers also looked for any association with cocaine dependence.
"We have identified a gene that we believe contributes to the risk for AD," said Foroud, "and is, furthermore, particularly important for those individuals who meet not only the DSM-IV criteria for AD but also the more stringent ICD-10 criteria. Furthermore, we found that this gene was also strongly associated with cocaine dependence."
Foroud said these results help support the theory that there are many genes, each with small individual effects, that contribute to the risk for AD. "Furthermore, this study highlights the importance of studying multiple phenotypes -- such as alcohol and cocaine dependence -- to try to understand how a gene might contribute to multiple disease risk." She and her colleagues plan to continue analyzing TACR3 in the COGA sample.
Dick is optimistic about the potential returns on future genetic research. "While any one gene on its own just has a very small effect in altering risk," she said, "once we catalog many of the genes involved in the development of dependence, this could lead to better individual-risk assessment, which may lead to improved prevention and intervention programs."
Results will be published in the June issue of Alcoholism: Clinical & Experimental Research and are currently available at OnlineEarly. Co-authors of the ACER paper, "The Tachykinin Receptor 3 (TACR3) is Associated with Alcohol and Cocaine Dependence," were: Leah Flury Wetherill, John I. Nurnberger, Jr., Xiaoling Xuei and Howard J. Edenberg of the Indiana University School of Medicine; John Kramer of the University of Iowa Carver College of Medicine in Iowa City; Jay A. Tischfield of the Human Genetics Institute at Rutgers University; and Marc A. Schuckit of the University of California, San Diego. The study was funded by the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse.
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