expression in oligodendrocytes and D1/D2 MSNs in individuals with AUD, suggests that PPP2R3C could be protective against AUD. Interestingly, expression of PPP2R3C was recently shown to be significantly associated with PAU in the nucleus accumbens – another part of the striatum – using a transcriptome-wide association analysis.15 A single variant, rs3742971, within a locus positively associated with PAU,5 was negatively associated with expression of the gene encoding the adenosine deaminase-like protein (ADAL) in four neuronal cell types (D1 MSNs, D2 MSNs, D1/D2 MSNs, and FS interneurons). ADAL had lower expression in individuals with AUD in these cells. In mice, elevated Adal levels contribute to low alcohol preference.84 This suggests that ADAL may be an important factor in the development of AUD. Our integrative analyses found three genes in astrocytes with strong evidence of being drivers of AUD. One of these, BTB/POZ domain-containing 3 (BTBD3, a transcription factor), has been shown to regulate compulsive-like behavior in mice,85 further evidence of this gene’s potential importance in addiction.
