biostudies-literatureWiegand ADeutsche ForschungsgemeinschaftGerman Federal Ministry of Education and Research (BMBF)10840https://www.ebi.ac.uk/biostudies/studies/S-EPMC12652996biostudies-literatureUnknown26(22)Alcohol use disorder (AUD) is associated with widespread epigenetic alterations, including changes in DNA methylation (DNAm). This multi-cohort study validated and extended previous findings on DNAm of <i>HECW2</i> and <i>GDAP1</i> in AUD, assessed sex differences, and explored DNAm in blood and brain tissue in humans and rats. DNAm was measured via pyrosequencing in human blood (N<sub>Ctrl</sub> = 341, N<sub>AUD</sub> = 258), postmortem frontal cortex (Brodmann area 9; discovery cohort: N<sub>Ctrl</sub> = 10, N<sub>AUD</sub> = 13, replication cohort: N<sub>Ctrl</sub> = 64, N<sub>AUD</sub> = 55) and rat blood and medial prefrontal cortex (N<sub>Ctrl</sub> = 16, N<sub>AUD</sub> = 15). Gene expression was assessed in human postmortem brain by quantitative real-time PCR. AUD-associated DNAm dInternational journal of molecular sciencesValidation of <i>GDAP1</i> and <i>HECW2</i> as Epigenetic Markers of Alcohol Use Disorder in Blood and Brain.PMC12652996NI13332/13-101ZX01909TRR265Koller GFriske MZill PHansson ACNieratschker VWiegand AEdelmann SSommer WHBakalkin GFischer LBender AfalseValidation of <i>GDAP1</i> and <i>HECW2</i> as Epigenetic Markers of Alcohol Use Disorder in Blood and Brain.Alcohol use disorder (AUD) is associated with widespread epigenetic alterations, including changes in DNA methylation (DNAm). This multi-cohort study validated and extended previous findings on DNAm of <i>HECW2</i> and <i>GDAP1</i> in AUD, assessed sex differences, and explored DNAm in blood and brain tissue in humans and rats. DNAm was measured via pyrosequencing in human blood (N<sub>Ctrl</sub> = 341, N<sub>AUD</sub> = 258), postmortem frontal cortex (Brodmann area 9; discovery cohort: N<sub>Ctrl</sub> = 10, N<sub>AUD</sub> = 13, replication cohort: N<sub>Ctrl</sub> = 64, N<sub>AUD</sub> = 55) and rat blood and medial prefrontal cortex (N<sub>Ctrl</sub> = 16, N<sub>AUD</sub> = 15). Gene expression was assessed in human postmortem brain by quantitative real-time PCR. AUD-associated DNAm d2025-01-01T00:00:00Z2025 Nov2026-05-19T03:14:02.324Z2026-05-19T03:10:38.449ZS-EPMC126529964130332810.3390/ijms262210840