Differences in ASE between subjects with and without AUD could be preexisting or the result of decades of excessive alcohol consumption. The functional SNPs, however, were detected by PASSPORT-seq in cultured cells in the absence of ethanol and therefore likely affect expression in the brain even in absence of ethanol exposure. Interestingly, the ASE of six SNPs in SK-N-BE(2) cells was altered by pharmacologically relevant concentrations of ethanol (10–20 mM); the direction of the acute alcohol response was opposite to the direction in the brain regions. Similar trends have been observed by others, e.g. acute alcohol exposure favors an anti-inflammatory response and chronic alcohol consumption favors proinflammatory cytokine release [29, 30]. The SNPs with in vitro ethanol-induced changes in allelic ratio are located in the 3′UTR of the three genes, PCDHB16, TMEM25, and SMPD4. PCDHB16 is a potential calcium-dependent cell-adhesion protein that may be involved in the establishment and maintenance of specific neuronal connections in the brain. The expression of clustered protocadherins has been shown to be strongly linked with selection for ethanol preference in mice [31, 32]. In addition,
