Gene linked to both alcoholism and depression

Sep 8 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.”