Twenty-six genes, or at least genetic material close to them, appear to be
implicated in alcoholism. The strongest candidates have been linked with other
types of substance abuse as well.
The largest dragnet for alcoholism genes conducted to date has produced
quite a catch, according to the National Institute on Drug Abuse (NIDA).
The scientific trawl, headed by George Uhl, M.D., Ph.D., chief of NIDA's
Molecular Neurobiology Research Branch, has identified 188 variants in genetic
material located at 51 different sites that may contribute to alcoholism.
“Previous studies established that alcoholism runs in families, but
this research has given us the most extensive catalog yet of the genetic
variations that may contribute to the hereditary nature of this
disease,” NIDA Director Nora Volkow, M.D., said in a press release.
Many of the 188 variants in genetic material are located near or even with
in 26 known genes. For example, three of the variants that cluster on
chromosome 7 are located very close to the AIP1 gene. This gene is expressed
primarily in the brain, where it interacts with atrophin and other proteins.
Three of the variants, on chromosome 7, lie within the flank of the gene that
codes for the receptor for neuropeptide S, which is thought to be an important
modulator of wakefulness and anxiety. Four of the variants, located on
chromosome 3, reside within the gene that makes the angiotensin II
Moreover, a number of the genetic variants have already been linked with
alcoholism in previous research. In fact, some of the variants also seem to
predispose to other kinds of addiction, regardless of ethnic background.
For example, four of the variants fingered in this study are located very
close to putative addiction genes identified in both European-American and
African-American polysubstance abusers. One of the variants identified in this
inquiry flanks five supposed addiction genes taken from
This level of replication is “extremely remarkable,” Uhl and
his team asserted in their research paper, which is in press with the
American Journal of Medical Genetics.
Of the variants he and his group have linked with alcoholism, Uhl told
Psychiatric News that those apparently playing the largest role in
the illness “also have evidence for association with methamphetamine
abuse (manuscript under review) and illegal substance abuse (manuscript in
press in Neuropsychiatric Genetics).”
Uhl said researchers were surprised to find that many of the candidate
alcoholism genes they have identified border genes that make cell-adhesion
molecules. “Neurons and glia grow, form, and maintain close contacts
with each other during development and in adulthood based on these
cell-adhesion molecular processes,” he explained.
The DNA samples that Uhl and his team used in this investigation were
collected through the Collaborative Study on the Genetics of Alcoholism (COGA)
during the 1990s (Psychiatric News, March 5, 2004).
The scientists used a technique to identify alcoholism genes that, as far
as they know, has not previously been used for this purpose. Called
association genome scanning, it can identify smaller chromosomal regions than
more traditional gene-identification techniques. Another advantage is that it
can pool Dna samples, which preserves confidentiality and reduces costs.
The study was funded by the National Institute on Drug Abuse and the
National Institute on Alcohol Abuse and Alcoholism.
“Pooled Association Genome Scanning for Alcohol Dependence
Using 104,268 SNPs: Validation and Use to Identify Alcoholism Vulnerability
Loci in Unrelated Individuals From the Collaborative Study on the Genetics of
Alcoholism” will be posted at<www.interscience.wiley.com/jpages/0148-7299>.▪