A large-scale meta-analysis of DNA methylation signatures of alcohol use disorder in the Psychiatric Genomics Consortium

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.

Authors

Institutions

Publication Details

Journal
Nature Mental Health
Published
2026-06-29
DOI
https://doi.org/10.1038/s44220-026-00666-w
Primary Topic
Epigenetics and DNA Methylation
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

A large-scale meta-analysis of DNA methylation signatures of alcohol use disorder in the Psychiatric Genomics Consortium

Katharina Domschke, Daniel F. Levey, Nancy Diazgranados, Eric Zillich et al.
Nature Mental Health
Epigenetics and DNA Methylation
article

A large-scale meta-analysis of DNA methylation signatures of alcohol use disorder in the Psychiatric Genomics Consortium

Katharina Domschke, Daniel F. Levey, Nancy Diazgranados, Eric Zillich, Negar Fani, Shaunna L. Clark, Rainer Spanagel, Dana B. Hancock, Edwin J. C. G. van den Oord, Miriam A. Schiele, Renato A Polimanti, Brion S. Maher, Joel Gelernter, Şeyma Katrinli, Karolina A. Åberg, William Copeland, Jeesun Jung, Stephanie H. Witt, Janitza L. Montalvo‐Ortiz, Sheila T. Nagamatsu, Jerome C. Foo, Julie D. White, Henry R. Kranzler, Lea Zillich, Diana L Nunez-Rios, Alicia K. Smith, Diana Avetyan, Eva Friedel, José Jaime Martínez‐Magaña, Eric O. Johnson, Ian R. Gizer, Angela P. Moissl, Falk W. Lohoff, David Goldman, Graciela E. Delgado, Marcus E Kleber, David W. Sosnowski, Sofia D'Augello, Natalie Merrill, Kirk C. Wilhelmsen, Abigail Powers, Winfried März, Jacqueline M. Otto, Brenda W. J. H. Penninx
article en

Abstract

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.

Nature Mental Health
University of Vermont (US), University of North Carolina at Chapel Hill (US), Synlab Czech (Czechia) (CZ), National Institutes of Health (US), Johns Hopkins University (US), Emory University (US), University of Alberta (CA), University of Freiburg (DE), RTI International (US), Virginia Commonwealth University (US), Regeneron (United States) (US), Medical University of Graz (AT), Heidelberg University (DE), University Hospital Heidelberg (DE), Yale University (US), VA Connecticut Healthcare System (US), Central Institute of Mental Health (DE), National Institute on Alcohol Abuse and Alcoholism (US), Ministry of AYUSH (IN), Synlab (Germany) (DE), Women and Children’s Health Research Institute (CA), Connecticut Health Foundation (US), Amsterdam University Medical Centers (NL), University Medical Centre Mannheim (DE), Renaissance Computing Institute (US), University of Missouri (US), Charité - Universitätsmedizin Berlin (DE), University of Pennsylvania (US), Heidelberg University (US), Vrije Universiteit Amsterdam (NL), RWTH Aachen University (DE), Texas A&M University (US)
Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung
Good health and well-being
Openalex Percentile: Top 12%
Epigenetics and DNA Methylation
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.