Panel of Genes May Identify Those With Increased Alcoholism Risk

A panel of 11 genes—essentially a panel of 66 different variants of those genes—appears to be successful in identifying people who are at increased genetic risk of developing alcoholism.

This finding was reported by Alexander Niculescu III, M.D., Ph.D., an associate professor of psychiatry at Indiana University, and colleagues May 20 in Translational Psychiatry.

The researchers used data from a genomewide study of alcoholism, as well as data from other alcoholism gene research, to identify 135 candidate alcoholism genes. They then compared those 135 genes with genes implicated in alcoholism in an animal model of the disease. This work enabled them to narrow the candidate alcoholism genes to only 11 and specifically to 66 variants of those genes.

They then assessed whether the 11 genes and the 66 variants could distinguish subjects with known alcohol dependence from controls in a German and a U.S. study population. The German cohort contained 1,601 individuals, the U.S. one 4,029 individuals.

The panel of genes and variants significantly distinguished subjects with alcohol dependence from controls in both groups. The researchers also found, in another U.S. cohort of 1,861 individuals, that the gene panel could significantly distinguish individuals with known alcohol abuse—a less-severe form of alcoholism than alcohol dependence—from controls.

Thus the panel of genes and their variants might eventually be used to identify individuals at genetic risk of alcoholism, Niculescu and his team suggested.

“Since alcoholism is a disease that does not exist if the exogenous agent [alcohol] is not consumed, the use of genetic information to inform lifestyle choices could be quite powerful,” they said in their report.

“The higher the genetic-risk prediction score, the higher the risk for alcoholism,” Niculescu explained in an interview with Psychiatric News. “Based on data from our American cohort of alcohol-dependent subjects and normal controls, the test was predictive at an individual level in 7 out of 10 people above a score of 48 (which was the average of alcohol-dependent subjects), and in 3 out of 4 people above a score of 60.”

The researchers also evaluated whether the strongest alcohol gene candidate—a gene called SNCA—could alone significantly distinguish alcohol-dependent subjects from controls and alcohol-abusing subjects from controls. They found that it could do so in both cases.

Asked whether the SNCA gene and variants could be used alone—without the other 10 genes and their variants—as a clinical test for alcoholism genetic risk, Niculescu indicated that he believes it could. “We just don’t want to rely on a single gene, as there might be heterogeneity in the population. SNCA by itself was better in [identifying] alcohol dependence; the panel worked somewhat better in [identifying] alcohol abuse. Both worked surprisingly well overall.”

Meanwhile, the findings have some other important implications, they suggested.

“The repertoire of genes potentially involved directly or indirectly in alcohol consumption and alcoholism may be quite large, similar to what we have previously seen for bipolar disorder and schizophrenia,” they said.

Many of the 11 genes they found linked to alcoholism have also been implicated in anxiety disorders, bipolar disorder, cocaine addiction, and schizophrenia. “This discovery means that genes are shared across disorders, which provides a basis for clinical comorbidity,” Niculescu said. “It also suggests that a better way to look at things is dimensional rather than categorical.”

And since “our genetic testing worked for both alcohol dependence and alcohol abuse, [it] suggests that these two diagnostic categories are actually overlapping, supporting the DSM-5 reclassification of a single category of alcohol use disorders,” the researchers noted.

“Drinking that is motivated by coping has been increasingly recognized in the literature as riskier for the development of alcoholism as compared to drinking for celebratory motives,” Sarah Book, M.D., an associate professor of psychiatry and medical director of the Center for Drug and Alcohol Programs of the Medical University of South Carolina, said in an interview. “This genomewide association study potentially adds a genetic association to this behavioral risk. Also, this panel of candidate genes may prove helpful for screening young people prior to alcohol exposure—identifying those at risk for the development of alcoholism and creating an opportunity for intervention to prevent the subsequent development of alcoholism.”

The research was funded by the National Institutes of Health, the Department of Veterans Affairs, and the National Genome Research Network of the German Federal Ministry of Education and Research. ■

An abstract of “Genetic Risk Prediction and Neurobiological Understanding of Alcoholism” can be accessed here.