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International study involving more than 3,700 participants identifies epigenetic changes associated with alcohol dependence / High correlation with alcohol consumption / Freiburg researcher establishes her own research group

An international research group led by the Medical Center – University of Freiburg has identified new biological markers for alcohol dependence. The researchers examined changes in DNA methylation in 3,775 individuals from seven study groups in Europe and the United States. DNA methylation refers to chemical changes in the genetic material that can influence genes without altering the DNA sequence itself. The results reveal epigenetic changes at 118 sites in the genome that are associated with alcohol dependence. Particularly compelling are the large sample size, the high consistency of the epigenetic signatures across different study groups, and their correlation with biological markers of alcohol consumption. The study was published on June 29, 2026, in the journal *Nature Mental Health*.

“Our findings show that alcohol dependence is accompanied by changes in the genome, the potential effects of which require further investigation,” says Dr. Lea Zillich of the Department of Psychiatry and Psychotherapy at the Medical Center – University of Freiburg and first author of the study. “Crucially, we were able to observe these changes across multiple studies. According to our findings, similar epigenetic signatures are present in both alcohol consumption and the clinical picture of alcohol dependence, and at the same time, we observed changes in DNA methylation that are specific to alcohol dependence.”

Alcohol dependence is one of the most common mental illnesses worldwide. It is associated with a loss of control over alcohol consumption, physical withdrawal symptoms, and serious health consequences. According to current estimates, about ten percent of the population is affected within a year. However, there is currently a lack of reliable biological markers that reflect the risk or course of the disease.

Changes in DNA as an Indicator of Alcohol Exposure

The research group analyzed so-called CpG sites. These are sections of DNA where methylation occurs particularly frequently and can impair gene function. The researchers combined data from seven independent studies, all of which were evaluated using standardized methods, thereby conducting the largest meta-analysis to date on DNA methylation in alcohol use disorder.

Of the 118 identified markers, 65 overlapped with previously known biological changes associated with alcohol consumption. This corresponds to 55.1 percent. This high degree of overlap provides clear evidence of the reliability of the results, as large sample sizes are already available for alcohol consumption. In contrast, two key markers were associated exclusively with alcohol dependence.

In addition, the research team developed a so-called methylation risk score. This score combines many individual DNA markers into a single overall value. In an independent group of 2,534 individuals, the score predicted heavy alcohol consumption with a predictive accuracy of 65.7 percent. Although this value is not sufficient for clinical use, the predictive performance is better than that of similar methylation risk scores in this field.

“The results provide an important foundation for identifying biological markers and mechanisms of alcohol dependence,” says Prof. Dr. Dr. Katharina Domschke, Medical Director of the Department of Psychiatry and Psychotherapy at the Medical Center – University of Freiburg. “At the same time, the study demonstrates how important large-scale international collaborations are for psychiatric research.”

Zillich is further expanding this research at the Medical Center – University of Freiburg. To this end, she is receiving a grant of more than two million euros from the Federal Ministry of Research, Technology, and Space (BMFTR). With this funding, she will establish her own research group starting in October 2026, which will further investigate biological markers for mental illnesses such as substance use disorders and, in particular, mood disorders, as well as their potential for improving treatment options for patients.

The researchers point out that the results do not yet allow for any conclusions as to whether the changes are a cause or a consequence of heavy alcohol consumption. Future studies will now investigate how the identified markers are related to gene function and changes in the brain, and whether new therapeutic approaches can be derived from these findings.

Original title of the study:A large-scale Meta-Analysis of DNA Methylation Signatures of Alcohol Use Disorder in the Psychiatric Genomics Consortium
DOI: 10.1038/s44220-026-00666-w
Link to the study: https://www.nature.com/articles/s44220-026-00666-w