A large-scale meta-analysis of DNA methylation signatures of alcohol use disorder in the Psychiatric Genomics Consortium
Year: 2026
Type: review
Abstract: Despite extensive research on DNA methylation signatures associated with alcohol use disorder (AUD), findings are often inconsistent. Here we conducted a large-scale meta-analysis of epigenome-wide association studies (EWASs) to identify reliable, reproducible epigenetic markers of AUD. Seven cohorts, comprising 3,775 individuals (1,325 with AUD), contributed to this meta-analysis. Downstream analyses included differentially methylated regions, overrepresentation analyses and the construction of a methylation risk score. We identified 118 significant CpG sites associated with AUD, with the strongest association found at cg24889777 ( P = 5.12 × 10 −17 ). CpG sites were enriched for pathways related to GTPase signaling, transmembrane transporter activity and EWAS signals of alcohol consumption. The methylation risk score explained 2.06% of the variance in alcohol consumption and predicted heavy drinking in an independent cohort ( N = 2,534, area under the curve = 0.657). This analysis offers key insights into the epigenetic mechanisms of AUD and lays the groundwork for future research on methylation risk scores for the diagnosis, prognosis and treatment of AUD.
Source: Nature Mental Health
Authors: Lea Zillich, Sofia D’Augello, Diana Avetyan, Graciela E. Delgado, Ian R. Gizer, Jeesun Jung, Seyma Katrinli, Marcus E. Kleber, Natalie Merrill, Angela P. Moissl-Blanke, Diana L. Núñez-Rios, Jacqueline M. Otto, Eric Zillich, Eva Friedel, Dana B. Hancock, Eric O. Johnson, José Jaime Martínez-Magaña, Sheila T. Nagamatsu, David W. Sosnowski, Julie D. White, Karolina A. Aberg, William E. Copeland, Nancy Diazgranados, Negar Fani, Joel Gelernter, David Goldman, Jerome C. Foo, Henry R. Kranzler, Daniel F. Levey, Winfried März, Brenda W. J. H. Penninx, Renato Polimanti, Abigail Powers, Alicia K. Smith, Rainer Spanagel, Edwin J. C. G. van den Oord, Kirk C. Wilhelmsen, Stephanie H. Witt, Katharina Domschke, Miriam A. Schiele, Brion S. Maher, Janitza L. Montalvo Ortiz, Shaunna L. Clark, Falk W. Lohoff
Institutions: University of Freiburg, Heidelberg University, University Medical Center Freiburg, Central Institute of Mental Health, Medizinische Fakultät Mannheim, RWTH Aachen University, University of Missouri, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Emory University, Yale University, VA Connecticut Healthcare System, Regeneron (United States), Charité - Universitätsmedizin Berlin, RTI International, Johns Hopkins University, Virginia Commonwealth University, University of Vermont, University of Alberta, Neuroscience and Mental Health Institute, Philadelphia VA Medical Center, University of Pennsylvania, Medical University of Graz, Synlab (Germany), Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Deutsches Zentrum für Psychische Gesundheit, University of North Carolina at Chapel Hill, Renaissance Computing Institute, Texas A&M University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7166544155