Investigating analogous brain regions in Macaques, we found that AUD differentially spliced genes tended to also demonstrate differential splicing in primate models of chronic alcohol use (see Supplementary Fig. S6). This overlap was more than we expected by chance, OR = 1.38, 95% CI [1.06, 1.77], p = 0.0126. We found significant, yet small, correlations of splicing events across brain regions in humans (r = 0.05–0.27; see Fig. 3), yet only 23 out of 713 genes (~ 3%) were differentially spliced across brain regions (see Supplementary Fig. S7). In the primate data, we found significant positive associations of differential splicing across brain regions when using the same individual primate samples (e.g., same monkeys but different tissues: PFC and CEA: r = 0.10, p = 2e−16). However, splicing associations across brain regions were negative when looking across different primate samples (NAc with the PFC: r = − 0.04 and NAc with CEA r = − 0.08, all p < 0.002). Altogether, these results suggest alcohol-related mRNA splicing is largely tissue-specific and that overlap across regions may be due to the same samples/individuals.
