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Gene Linked to Both
Alcoholism and Depression
St. Louis, Sept.
2, 2004 — A national team of investigators led by psychiatric geneticists at
Washington University School of Medicine in St. Louis has identified a gene that
appears to be linked to both alcoholism and depression.
The study, published in the September issue of the
journal Human Molecular Genetics, is the first to identify a specific gene
associated with both depression and alcoholism.
“Clinicians have observed a connection between
these two disorders for years, so we are excited to have found what could be a
molecular underpinning for that association,” says principal investigator
Alison M. Goate, D. Phil., the Samuel and Mae S. Ludwig Professor of Genetics in
Psychiatry, professor of genetics and professor of neurology at the School of
Medicine.
The research is part of the national Collaborative
Study on the Genetics of Alcoholism (COGA), an ongoing project involving the
collection of interviews and DNA samples from more than 10,000 people with
alcohol dependence and their families. Participants in the COGA study usually
have several family members with alcohol dependence. Because depression and
alcoholism often occur together, many COGA participants also suffer from
depression.
The Washington University team analyzed DNA from
2,310 people from 262 families in which at least three members were alcoholic.
Using DNA-analysis techniques, the researchers found that one region on
chromosome 7 looked remarkably similar in most alcoholics.
They then examined DNA from depressed COGA
participants, independent of alcohol usage and found that the same
distinguishing region on chromosome 7 also looked similar in most depressed
individuals. In addition, participants with both depression and alcoholism were
the most likely to have these similarities on chromosome 7.
Having identified the general region of interest on
chromosome 7, the team began trying to isolate specific key genes within that
region. They started with CHRM2, a gene related to a type of cellular receptor
involved in many important brain functions, including attention, learning,
memory and cognition. Goate’s team made this gene their starting point because
in July, a group led by researchers at the State University of New York Health
Science Center in Brooklyn found that differences in electrical activity might
mark susceptibility to alcoholism and that these unusual brain activity patterns
are linked to CHRM2.
Goate’s team found that the gene was strongly
associated both with alcoholism and depression. The association was strongest in
those individuals who had both disorders.
“It looks as if this might be a susceptibility
gene that puts a person at risk for developing both depression and
alcoholism,” she says.
The researchers believe normal variations in the
gene either protect an individual or make that person more susceptible to
alcoholism and/or depression. Their next step will be to identify specific
variants in the gene that lead to differences in disease risk.
“It’s likely that a combination of
susceptibility genes and environmental risk factors lead to the development of
alcoholism, depression or the combination of those disorders,” she says. “As
we identify those genes, we hope to find out exactly what functional changes in
the gene increase or decrease disease risk.”
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Wang JC, Hinrichs AL, Stock H, Budde J, Allen R,
Bertelsen S, Kwon JM, Wu W, Dick DM, Rice JP, Jones K, Nurberger JI, Tischfield
J, Porjesz B, Edenberg HJ, Hesselbrock V, Crowe R, Schuckit M, Begleiter H,
Reich T, Goate AM, Beirut LJ. Evidence of common and specific genetic effects:
association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with
alcohol dependence and major depressive syndrome. Human Molecular Genetics, vol.
13:17, pp. 1903-1911, Sept. 1, 2004.
Related publication:
Jones K, Porjesz B, Almasy L, Beirut LJ, Goate AM,
Hinrichs AL, Kwon JM, Rice JP, Rohrbaugh J, Stock H, Wang JC, Wu W, Bauer LO,
Chorlian DB, Dick DM, Edenberg HJ, Foroud T, Hesselbrock V, Kuperman S,
Nurnberger JI, O’Connor SJ, Schuckit M, Stimus AT, Reich T, Begleiter H.
Linage and linkage disequilibrium of evoked EEG oscillations with CHRM2 receptor
gene polymorphisms: Implications for human brain dynamics and cognition.
International Journal of Psychophysiology, vol. 53, pp. 75-90, July 1, 2004.
This research was funded by the National Institute
of Alcohol Abuse and Alcoholism of the National Institutes of Health.
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