|NIH Researchers Complete Unprecedented Genetic
Study That May Help Identify People Most at Risk for Alcoholism
Scan of human genome may provide important new tools for prevention
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
“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
“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
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
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
The National Institute on Drug Abuse and the National Institute
on Alcohol Abuse and Alcoholism are components of the National
Institutes of Health, U.S. Department of Health and Human Services.
NIDA supports most of the world’s research on the health aspects
of drug abuse and addiction. The Institute carries out a large
variety of programs to ensure the rapid dissemination of research
information and its implementation in policy and practice. Fact
sheets on the health effects of drugs of abuse and information
on NIDA research and other activities can be found on the NIDA
home page at http://www.drugabuse.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.