Study reveals genetic links between alcohol dependence and psychiatric disorders

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

The new analysis, from the substance use substances working group of the Genomic Psychiatry Consortium, adds to the current understanding of alcohol dependence, a complex disease influenced by genes, the environment and their interactions.

The gene conclusively associated with the risk of alcohol dependence regulates the rate at which the body metabolizes alcohol. The effects of other genes were not important enough to achieve individual statistical significance – although 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 can contribute to alcohol problems as a way to develop improved and more personalized treatments.

The study is published online November 26 in the journal Nature Neuroscience.

"According to current estimates, one in eight Americans is suffering from alcohol addiction," said lead author Arpana Agrawal, PhD, a professor of psychiatry at the University of Washington's School of Medicine at St. John's Hospital. Louis. "And the gene we have identified has a protective effect, but is by no means the only thing that affects the risk of alcohol addiction.We know that environmental factors also play a role. Genetic susceptibility to alcohol dependence stems from the weak effects of a very large number of variants across the genome ".

The analysis compared the genetic variants of nearly 15,000 people diagnosed with alcohol dependence to nearly 38,000 people who did not receive this diagnosis.

To bring together such a large sample, Agrawal – with colleagues from Yale University's Faculty of Medicine, the Indiana University School of Medicine, the Broad Institute, and the University of California, is one of the world's leading universities. other centers around the world – analyzed data from 28 genetic studies on alcoholism conducted in eight countries. . But researchers believe that even larger studies will be needed in the future as genetic studies of other psychiatric disorders have required the DNA of 40,000 to 100,000 patients to allow researchers to find out more. isolate dozens of genetic variants linked to diseases such as schizophrenia and depression.

"As we analyze other alcohol-dependent individuals, we should be able to find other genomic regions affecting the risk of alcohol dependence," said the author. first author, Raymond Walters, Broad Institute of MIT and Harvard. "We know that other areas of the DNA have small effects on risk, but it will require a significant increase in the size of our sample before we can robustly identify these variants."

The only gene that stands out, called ADH1B, governs how the body converts alcohol into a substance called acetaldehyde. Variants of the gene accelerate the conversion to acetaldehyde, an unpleasant compound that has a protective effect, reducing the risk of excessive consumption of alcohol or alcoholism. The current drug Disulfuram (Antabuse) acts on the same metabolic processes as the gene variants identified in this study.

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

"There were genetic linkages with both other psychiatric disorders, such as depression, and the use of cigarettes and other drugs like cannabis," said Joel Gelernter, MD , from the Faculty of Medicine at Yale University. "As we study more people, we hope to be able to determine to some extent to what extent this correlation, or shared risk, is attributable to alcoholism, and to what extent -be the consequence of these other troubles. "

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

"There have been very extensive genetic studies on Europeans, but not so much research on African populations to try to understand what genetic factors are at the root of the risk of alcoholism," said Howard J. Edenberg, PhD, from the Faculty of Medicine at Indiana University. "In the future, we will have to study a much larger number of people from non-European populations because we know less about the genetic factors that affect their risk.As our study has shown, these factors may differ. from one population to the other. "

The researchers also found that the genetic factors associated with the simple consumption of alcohol were a little different from the genetic factors contributing to alcohol dependence. In other words, at least at the genetic level, there is a difference between just drinking alcohol, even large amounts of alcohol, and becoming dependent on it.

"People suffering from alcohol addiction usually drink a lot, but they also have other problems related to their alcohol consumption, such as the loss of control over the timing and quantity that they have. They drink, "said Agrawal. "I think it's likely that, as the sample sizes of our studies increase, we might find new DNA variants related to these problematic aspects of alcohol dependence," he says. but probably not for the typical consumption of alcohol "

She said that these large samples of people with and without a diagnosis of alcohol addiction would be key to future discoveries on genetic contributions to alcoholism.

"The risk conferred by the ADH1B gene is one of the most potent monogenic effects seen in people with psychiatric illness, but overall, it only explains why it is safe for people to take it. a small part of the risk, "said Agrawal. "Many extra gene variants contribute little to the risk of alcoholism, but to find them, we will have to study more people."