{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:14:26Z","timestamp":1777414466872,"version":"3.51.4"},"posted":{"date-parts":[[2025,9,2]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Despite extensive research on DNA methylation (DNAm) signatures associated with alcohol use disorder (AUD), findings are often inconsistent and not replicated. We conducted a large-scale meta-analysis of epigenome-wide association studies (EWAS) to identify reliable, reproducible epigenetic markers of AUD.<\/jats:p>\n                <jats:p>Seven cohorts, comprising 3,775 individuals (1,325 with AUD), contributed to this meta-analysis within the framework of the Psychiatric Genomics Consortium Substance Use Disorders Epigenetics Working Group. Downstream analyses included the identification of differentially methylated regions, overrepresentation analyses, and the construction of a methylation risk score (MRS).<\/jats:p>\n                <jats:p>\n                  We identified 118 significant CpG sites associated with AUD, with the strongest association found at cg24889777 (\n                  <jats:italic>p<\/jats:italic>\n                  =5.12\u00d710\n                  <jats:sup>-17<\/jats:sup>\n                  ) in the long non-coding RNA LOC100505942. CpG sites were enriched for pathways related to GTPase signaling and transmembrane transporter activity, as well as EWAS signals of alcohol consumption. The MRS explained 10.44% of variance in heavy drinking in an independent cohort (N=2,534, AUC=0.657).\n                <\/jats:p>\n                <jats:p>This large-scale meta-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 in AUD.<\/jats:p>","DOI":"10.1101\/2025.08.29.25334705","type":"posted-content","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T23:05:11Z","timestamp":1756854311000},"source":"Crossref","is-referenced-by-count":1,"title":["DNA Methylation Signatures of Alcohol Use Disorder \u2013 A large-scale Meta-Analysis in the Psychiatric Genomics 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