A scientific team from the U.S. and Germany reports that a group of 11 genes can successfully predict whether an individual is at increased risk of alcoholism.
The gene panel is highly accurate in its differentiation of alcoholics from controls at a population level, and less so at an individual level, likely due to the major and variable role environment plays in the development of the disease in each individual, noted the authors of the research paper (“Genetic risk prediction and neurobiological understanding of alcoholism”), which appears in Translational Psychiatry. Nevertheless, such a test could identify people who are at higher or lower risk for the disease, they add.
“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 Alexander B. Niculescu III, M.D., Ph.D., principal investigators and 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 researchers incorporated data from a German genome-wide study of alcoholism with data from a variety of other types of research into genetic links to alcoholism using a system called Convergent Functional Genomics. The work produced a group of 135 candidate genes.
The scientists then looked at the overlap between those 135 genes and genes whose expression activity was changed in a mouse model of stress-reactive alcoholism. Analysis of the mouse model, which enables researchers to zero in on key genes that drive behavior without the myriad environmental effects that are present in humans, narrowed the candidates down to the panel of 11 genes and 66 variations of those genes called single-nucleotide polymorphisms.
The researchers then determined that the panel of 11 genes could be used to differentiate between alcoholics and nonalcoholics (controls) 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 U.S., and a third group from Germany.
“These genes fall into a series of biological pathways involved in signal transduction, transmission of nerve impulse (including myelination), and cocaine addiction,” wrote the investigators. “Overall, our work provides leads toward a better understanding of illness, diagnostics, and therapeutics including treatment with omega-3 fatty acids. We also examined the overlap between the top candidate genes for alcoholism from this work and the top candidate genes for bipolar disorder, schizophrenia, anxiety from previous CFG analyses conducted by us, as well as cross-tested genetic risk predictions. This revealed the significant genetic overlap with other major psychiatric disorder domains, providing a basis for comorbidity and dual diagnosis, and placing alcohol use in the broader context of modulating the mental landscape.”