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NIH unprecedented genetic study may help identify people most at risk for alcoholism
August 28, 2006Scan of human genome may provide important new tools for prevention and treatment
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. The study can be viewed online and will be published in the December 2006 issue of the American Journal of Medical Genetics Part B (Neuropsychiatric Genetics).
"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."
"This is an important contribution to studies of the genetics of alcoholism and co-occurring substance use disorders," adds Dr. Ting-Kai Li, director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). "The findings will open many new avenues of research into common factors in genetic vulnerability and common mechanisms of disease."
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, included Ms. Catherine Johnson, Ms. Donna Walther, Dr. Tomas Drgon, and Dr. Qing-Rong Liu. Their team 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), a study funded by NIAAA that included Dr. Howard Edenberg, Dr. Tatiana Foroud, and Dr. John Rice, who are coauthors of the paper. These samples had been analyzed previously to look for genetic associations to alcoholism, but the resolution and coverage achieved in the present study are unprecedented.
"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."
The term "genome" refers to the total genetic information of a particular organism. The normal human genome consists of about 3 billion base pairs of DNA in each set of chromosomes from one parent.
The term "genetic variation" is used to describe differences in the sequence of DNA among individuals. Genetic variation plays a role in whether a person has a higher or lower risk for getting particular diseases.
NIH/National Institute on Drug Abuse
"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."
"This is an important contribution to studies of the genetics of alcoholism and co-occurring substance use disorders," adds Dr. Ting-Kai Li, director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). "The findings will open many new avenues of research into common factors in genetic vulnerability and common mechanisms of disease."
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, included Ms. Catherine Johnson, Ms. Donna Walther, Dr. Tomas Drgon, and Dr. Qing-Rong Liu. Their team 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), a study funded by NIAAA that included Dr. Howard Edenberg, Dr. Tatiana Foroud, and Dr. John Rice, who are coauthors of the paper. These samples had been analyzed previously to look for genetic associations to alcoholism, but the resolution and coverage achieved in the present study are unprecedented.
"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."
The term "genome" refers to the total genetic information of a particular organism. The normal human genome consists of about 3 billion base pairs of DNA in each set of chromosomes from one parent.
The term "genetic variation" is used to describe differences in the sequence of DNA among individuals. Genetic variation plays a role in whether a person has a higher or lower risk for getting particular diseases.
NIH/National Institute on Drug Abuse
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