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

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 cohort...

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Main Authors: Zillich, Lea (Author) , D’Augello, Sofia (Author) , Avetyan, Diana (Author) , Delgado Gonzales de Kleber, Graciela (Author) , Gizer, Ian R. (Author) , Jung, Jeesun (Author) , Katrinli, Seyma (Author) , Kleber, Marcus E. (Author) , Merrill, Natalie (Author) , Moissl-Blanke, Angela P. (Author) , Núñez-Rios, Diana L. (Author) , Otto, Jacqueline M. (Author) , Zillich, Eric (Author) , Friedel, Eva (Author) , Hancock, Dana B. (Author) , Johnson, Eric O. (Author) , Martínez-Magaña, José Jaime (Author) , Nagamatsu, Sheila T. (Author) , Sosnowski, David W. (Author) , White, Julie D. (Author) , Aberg, Karolina A. (Author) , Copeland, William E. (Author) , Diazgranados, Nancy (Author) , Fani, Negar (Author) , Gelernter, Joel (Author) , Goldman, David (Author) , Foo, Jerome Clifford (Author) , Kranzler, Henry R. (Author) , Levey, Daniel F. (Author) , März, Winfried (Author) , Penninx, Brenda W. J. H. (Author) , Polimanti, Renato (Author) , Powers, Abigail (Author) , Smith, Alicia K. (Author) , Spanagel, Rainer (Author) , van den Oord, Edwin J. C. G. (Author) , Wilhelmsen, Kirk C. (Author) , Witt, Stephanie (Author) , Domschke, Katharina (Author) , Schiele, Miriam A. (Author) , Maher, Brion S. (Author) , Montalvo Ortiz, Janitza L. (Author) , Clark, Shaunna L. (Author) , Lohoff, Falk W. (Author)
Format: Article (Journal)
Language:English
Published: 29 June 2026
In: Nature Mental Health
Year: 2026, Pages: 1-11
ISSN:2731-6076
DOI:10.1038/s44220-026-00666-w
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s44220-026-00666-w
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s44220-026-00666-w
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Author Notes: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
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Summary: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.
Item Description:Gesehen am 29.06.2026
Physical Description:Online Resource
ISSN:2731-6076
DOI:10.1038/s44220-026-00666-w

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