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Chunk #32 — Discussion

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Genome- and transcriptome-wide splicing associations with alcohol use disorder.
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The takeaways from our study are consistent with previous analyses of these data. Both our study and the Van Booven et al., study7 found: (1) thousands of differentially spliced events between individuals with AUD and controls, with (2) largely tissue-specific findings and (3) different magnitudes of splicing associations by brain region as well as (4) more significant splicing associations with AUD than differential expression associations. Also, at the genetic level, we identified an order of magnitude more sQTLs than the previously reported (and validated) expression QTLs (eQTLs) with AUD14. These results are consistent with previous analyses suggesting alternative mRNA splicing elicits robust genetic and neurotranscriptional correlates with psychiatric traits2 and calls for additional research to better characterize the gene isoform architecture of mental illness and substance abuse.