|Study Reveals New Genes for Excessive Alcohol Drinking
Researchers supported by the National Institute on Alcohol Abuse and Alcoholism
(NIAAA), part of the National Institutes of Health (NIH), have identified new
genes that may contribute to excessive alcohol consumption. The new study, conducted
with strains of animals that have either a high or low innate preference for
alcohol, provides clues about the molecular mechanisms that underlie the tendency
to drink heavily. A report of the findings appears in the April 18, 2006 issue
of Proceedings of the National Academy of Sciences.
“These findings provide a wealth of new insights into the molecular determinants
of excessive drinking, which could lead to a better understanding of alcoholism,” notes
NIAAA Director Ting-Kai Li, M.D. “They also underscore the value that animal
models bring to the investigation of complex human disorders such as alcohol
Mice that have been selectively bred to have either a high or low preference
for alcohol have been a mainstay of alcohol research for many years, allowing
investigators to study diverse behavioral and physiological characteristics of
alcohol dependence. In the current study, NIAAA grantee Susan E. Bergeson, Ph.D.,
of the University of Texas (UT) at Austin, and a multi-site team of scientists
participating in NIAAA’s Integrative Neuroscience Initiative on Alcoholism (INIA)
used microarray techniques to study gene expression in the brains of these animals.
Microarrays are powerful tools that investigators use for comprehensive analyses
of gene activity.
“Microarrays allow us to look at the full complement of genes that are active
in the brains of animals bred to exhibit very different alcohol drinking behaviors,” said
Dr. Bergeson, an Assistant Professor of Neurobiology in UT’s Waggoner Center
for Alcohol and Addiction Research. When a gene is activated, cellular machinery
transcribes certain parts of the gene’s DNA into messenger RNA (mRNA), which
is the body's template for creating proteins. The complete set of transcribed
mRNA in a tissue is termed the “transcriptome.”
Dr. Bergeson and her INIA colleagues examined brain transcriptomes of nine strains
of mice, each differing in their voluntary alcohol consumption.
“By measuring total gene expression in brains of each of the mouse models we
could explore which transcripts are consistently changed in different genetic
models of high and low alcohol intake and thereby define the transcriptional
signatures of genetic predisposition to high and low alcohol consumption,” said
The researchers employed novel statistical techniques to identify nearly 4,000
differentially expressed genes between the high and low alcohol drinking mouse
strains and to narrow the focus to 75 primary candidate genes. In addition, a
comparison of the mouse data with human genetic studies revealed that genes with
significant expression differences reside in chromosomal regions that previously
were shown to be associated with human alcoholism.
Numerous pathways, as well as genes whose functions are currently unknown, may
contribute to the genetic predisposition to drink high amounts of alcohol, notes
Dr. Bergeson. “Our results will allow us to begin to focus on targets never previously
implicated in excessive drinking. For example, genetic studies have shown that
chromosome 9 contains genes that may regulate alcohol consumption in mice. Our
analyses allowed us to narrow our focus from thousands of genes in that region
“This first microarray-based analysis of a behavioral trait reveals many new
research opportunities and exemplifies the rich collaborative potential of NIAAA’s
INIA consortium,” adds Dr. Li.
The National Institute on Alcohol Abuse and Alcoholism, part of the National
Institutes of Health, is the primary U.S. agency for conducting and supporting
research on the causes, consequences, prevention, and treatment of alcohol
abuse, alcoholism, and alcohol problems and disseminates research findings
to general, professional, and academic audiences. Additional alcohol research
information and publications are available at www.niaaa.nih.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 http://www.nih.gov.