Genetic link between alcohol dependence and psychiatric disorders

Genetic link between alcohol dependence and psychiatric disorders

In the largest study of genetic factors linked to alcohol dependence, an international team of researchers identified a gene known to affect risk, and they determined that many other genes also contribute to risk for alcohol dependence to a lesser degree. In addition, the study linked genetic factors associated with alcohol dependence to other psychiatric disorders, such as depression, and showed that genetic factors associated with typical drinking sometimes are different from those associated with alcohol dependence.

The new analysis, from the Substance Use Disorders working group of the Psychiatric Genomics Consortium, adds to the current understanding of alcohol dependence, a complex disorder influenced by genes, environment and their interactions.

The gene that was conclusively associated with risk of alcohol dependence regulates how quickly the body metabolizes alcohol. The effects of other genes weren't big enough to reach statistical significance individually -- even though this study involved more than 50,000 people -- but their combined effects were significant.

The goal of the research is to better understand how genes may contribute to alcohol problems as a way to develop improved and more personalized treatments. The study is published in the journal Nature Neuroscience.

The analysis compared genetic variants from nearly 15,000 individuals diagnosed with alcohol dependence to nearly 38,000 people who did not have that diagnosis.

To gather such a large sample, the researchers analyzed data from 28 genetic studies of alcoholism in eight countries. But the researchers believe even larger studies will be needed in the future because genetic studies of other psychiatric disorders have required DNA from between 40,000 and 100,000 patients to allow researchers to isolate dozens of gene variants related to conditions such as schizophrenia and depression.

The one gene that did stand out, called ADH1B, regulates how the body converts alcohol to a substance called acetaldehyde. Variants in the gene speed the conversion to acetaldehyde, an unpleasant compound, and that has a protective effect, making people less likely to drink heavily or become alcoholics. A current drug, Disulfuram (Antabuse) works on the same metabolic processes as the gene variants identified in this study.

The researchers found that the genetic risk factors related to alcohol dependence also were linked to risk for other psychiatric disorders, such as depression, schizophrenia, ADHD and the use of cigarettes and marijuana. They plan to continue investigating those links between genetic susceptibility to alcohol dependence and risk for other types of psychiatric illness.

A key aspect of the new study is that it included genetic data from people of European (46,568) and African (6,280) ancestry. Although the same ADH1B gene was linked to alcoholism risk both in people of European ancestry and African ancestry, the researchers found that different variants in the gene altered risk in the two populations. Other research has revealed that the same variation in the same gene as occurs in Europeans also influences risk in people of Asian descent, but that data was not included in this study.

The researchers also found that the genetic factors related to simply drinking alcohol were a little different from the genetic factors that contributed to alcohol dependence. In other words, at least at the genetic level, there's a difference between simply drinking alcohol, even large amounts of alcohol, and becoming dependent on it.

"People suffering from alcohol dependence generally drink a great deal, but they also experience other problems related to their drinking, like losing control over when and how much they drink," the author explained. "I think it's likely that as the sample sizes of our studies increase, we may find new DNA variants related to these problematic aspects of alcohol dependence but possibly not related to typical drinking."

https://medicine.wustl.edu/news/alcohol-dependence-psychiatric-disorders-share-genetic-links/
 
https://www.nature.com/articles/s41593-018-0275-1

 
 
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