To our knowledge, this is the largest transcriptome analysis comparing PFC of alcohol-dependent cases and controls. The present study identified 129 genes (FDR < 0.05) that were differentially expressed in alcohol-dependent subjects (Supplementary table 1). FKBP5, a well studied gene that is asoociated with alcohol use28–31, showed increased expression in the PFC of alcohol-dependent subjects in our differential gene expression analysis (l2FC 0.27; P = 4.57 × 10−7). Other studies have also shown that FKBP5 plays a role in alcohol drinking behaviors in rodents28,29 and humans32. FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity30. Qiu and colleagues30 reported that Fkbp5 KO mice exhibited increased alcohol consumption compared with wild-type mice. Another study has shown that the absence of Fkbp5 enhances sensitivity to alcohol withdrawal in mice33. Recent findings also suggested that Fkbp5 expression in mesocorticolimbic dopaminergic regions is associated with early life-stress mediated sensitivity to alcohol drinking and that there is a gene–environment interaction among FKBP5 genotype and parent–child relationship that influences alcohol drinking.
