Researchers at the Molecular Neurobiology Branch of the National Institute on Drug Abuse (NIDA), National Institutes of Health, have completed the most comprehensive scan of the human genome to date linked to the ongoing efforts to identify people most at risk for developing alcoholism. This study represents the first time the new genomic technology has been used to comprehensively identify genes linked to substance abuse.
“Tools such as pooled data genome scanning give us a completely new way of looking at complex biological processes, such as addiction,” says Dr. Elias A. Zerhouni, director of the National Institutes of Health. “The ability to pinpoint genes in the human genome responsible for disease has the potential to revolutionize our ability to treat and even prevent diseases.”
“Previous studies established that alcoholism runs in families, but this research has given us the most extensive catalogue yet of the genetic variations that may contribute to the hereditary nature of this disease,” says NIDA Director Dr. Nora D. Volkow. “We now have new tools that will allow us to better understand the physiological foundation of addiction.”
NIDA researchers found genetic variations clustered around 51 defined chromosomal regions that may play roles in alcohol addiction. The candidate genes are involved in many key activities, including cell-to-cell communication, control of protein synthesis, regulation of development, and cell-to-cell interactions. For example, one gene implicated in this study--the AIP1 gene--is a known disease-related gene expressed primarily in the brain, where it helps brain cells set up and maintain contacts with the appropriate neighboring cells. Many of the nominated genes have been previously identified in other addiction research, providing support to the idea that common genetic variants are involved in human vulnerability to substance abuse.
The scientists, led by Dr. George Uhl, developed, validated, and applied a new genetic platform that allowed them to generate the equivalent of more than 29 million individual genotypes and to analyze 104,268 genetic variations from unrelated alcohol-dependent and control individuals. The scientists used DNA samples that were collected by investigators of the Collaborative Study on the Genetics of Alcoholism (COGA),
“The observations from this study provide a graphic display of the close relationships between genetic vulnerability to alcoholism and genetic vulnerability to other addictions,” says Dr Uhl. “Ongoing and future studies will help us to identify how the variations in these candidate genes contribute to differences in addiction vulnerability.”
“We know that vulnerabilities to substance abuse involve complex traits with strong genetic influences,” adds Dr. Volkow. “Finding ways to identify who is most physiologically vulnerable to addiction will be a tremendous step towards more effective prevention and treatment approaches.”
Reference: The study was published online 07/08/06 and will be published in the December 2006 issue of the American Journal of Medical Genetics Part B (Neuropsychiatric Genetics).