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Chunk #29 — Results — Cell Type-specific Gene-Regulatory Mechanisms in AUD

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Integrated Single-Cell Multiomic Profiling of Caudate Nucleus Suggests Key Mechanisms in Alcohol Use Disorder.
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We saw a modest decrease in expression of myelin basic protein (MBP), a major component of myelin, in oligodendrocytes from individuals with AUD (padj = 0.11). Graph-based subclustering of oligodendrocytes revealed three major subclusters, one of which had significantly lower MBP expression than the other two (Fig. 6G). This cluster was marked by high expression of OLIG2. We found 616 motifs with activity significantly associated with AUD (p < 0.05), including OLIG2 (p = 0.028, Supplementary Table 17) (Fig. 6H). This gene was identified as a ‘driver’ by LINGER, having higher regulatory activity in individuals with AUD based on the chromatin accessibility of its target genes.