Blood‐Based Epigenetic Signatures in Brazilian Males With Alcohol Use Disorder

Alcohol use disorder (AUD) is a chronic and progressive disease that affects individuals worldwide. AUD individuals exhibit epigenetic alterations across tissues, mainly in the brain. Despite advances in the field, there is a gap in epigenome-wide association studies (EWAS) conducted in a Brazilian cohort that is genetically and culturally diverse. This study aimed to describe an exploratory EWAS conducted in Brazilian males with AUD and to identify DNA methylation signatures associated with brain-related biological pathways. Peripheral blood samples were collected from 54 patients with AUD in the early stages of withdrawal (AUD group) and 70 control individuals (CON group) (Brazil, São Paulo). Genome-wide DNA methylation was assessed using the Infinium MethylationEPIC BeadChip v2.0. We identified four differentially methylated loci in genes involved in intracellular signalling and cellular stress responses. Focusing on the nervous system, enrichment analyses revealed pathways related to neuronal/axon development and synaptic organization hypomethylated in the AUD group (p. adjust < 0.05). Differentially methylated regions (DMRs) showed hypomethylation in regulatory and exonic regions of ABAT, DLX5, PHGDH, TRPM2 and GABBR1 genes, which are within the enriched pathways. In conclusion, to the best of our knowledge, this is the first EWAS in a Brazilian cohort with AUD to identify alterations in DNA methylation, highlighting genes and pathways involved in neurogenesis, synaptic and GABAergic signalling. These epigenetic modifications suggest an impact of chronic alcohol consumption on critical biological processes of the CNS, potentially contributing to the cognitive and behavioural impairments observed in AUD. The results reinforce the importance of epigenetic studies in mixed-race populations.