of the effect of alcohol on lipid metabolism and cardiovascular risk141. A methylome-wide analysis of 1,287 adolescents showed that methylation of the SPDEF (E-twenty-six transcription factor) gene moderated the association of psychosocial stress with alcohol and tobacco abuse142. Epigenetic dysregulation appears to be involved in reprogramming the medial prefrontal cortex after prolonged exposure to cycles of alcohol intoxication and withdrawal, which promotes the escalation of voluntary alcohol intake and aversion-resistant alcohol seeking143 (i.e., AUD). Epigenome-wide analysis in patients during acute alcohol withdrawal and after 2 weeks of recovery as well as in age-matched controls showed that, although acute alcohol withdrawal in severely dependent patients was associated with extensive epigenetic changes, the differences between patients and controls diminished after recovery, suggesting partial reversibility of alcohol- and withdrawal-related methylation144. Leveraging epigenetic clock algorithms [G]145, epigenetic ageing in AD appears to be tissue-specific with positive age acceleration in blood and liver, but no significant effect was observed likely due to the small sample size (N<50)146.
