Gene Panel May Be Able to Identify Existing and Potential Alcoholics

A Convergent Functional Genomics (CFG) approach was used to discover genes involved in alcoholism in a study that has implications for genetic testing to assess risk for developing an illness before the illness manifests itself clinically.

The CFG technique was developed by Dr. Alexander Niculescu of the Indiana University School of Medicine (Indianapolis, USA), and collaborators starting in 1999. It is an approach for identifying and prioritizing candidate genes and biomarkers for complex psychiatric and medical disorders by integrating and tabulating multiple lines of evidence including gene expression and genetic data from human studies and from animal model work. CFG generates a signal that is predictive and is reproducible in independent studies, as opposed to the fit-to-cohort aspect of classic human genetic studies like the genome-wide association study (GWAS), where the issue of genetic heterogeneity makes the top statistically significant findings from even large size studies less reproducible in independent studies.

In the current work, Dr. Niculescu and collaborators in the United States and Germany used CFG to analyze data from a German genome-wide study of alcoholism and data from a variety of other studies into genetic links to alcoholism. The analysis produced a group of 135 candidate genes. They then used a stress-reactive animal model of alcoholism, the D-box binding protein (DBP) knockout mouse, to identify genes expressed by both the alcoholic humans and the stress-reactive alcoholic mice.

This process yielded a panel of 11 genes with 66 single-nucleotide polymorphisms (SNPs). The investigators found that this panel of 11 genes could be used to differentiate between alcoholics and non-alcoholics in three different research populations for which genetic data and information about alcohol consumption were available: a group of Caucasian subjects and a group of African American subjects from the USA, and a third group from Germany.

"This powerful panel of just 11 genes successfully identified who has problems with alcohol abuse and who does not in tests in three patient populations on two continents, in two ethnicities and in both genders," said senior author Dr. Alexander B. Niculescu, associate professor of psychiatry and medical neuroscience at the Indiana University School of Medicine. "We believe this is the strongest result to date in the field of alcoholism and offers a comprehensive—though not exhaustive—window to the genetics and biology of alcoholism."

The study was published in the May 20, 2014, issue of the journal Translational Psychiatry.

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