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Chunk #12 — Results — Widespread differences in gene expression in diverse cell types are associated with 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 performed differential gene expression analyses in the thirteen major cell types in which there were greater than 50 cells in more than 10 individuals with and 10 without AUD. We used a pseudobulk approach, summing counts across cells within each sample for each cell type, with sex, age, and ethnic origin as covariates. Samples were removed on a cell type-specific basis if they contained fewer than 50 cells of that type (Supplementary Data 7). Eight cell types each contained over 100 DEGs (FDR < 0.05; Fig. 2a; Supplementary Data 7). We identified many changes in oligodendrocytes, astrocytes, and neurons, especially D1 and D2 MSNs. In each of these cell types, more of the DEGs had higher expression in individuals with AUD. Although the number of DEGs tended to be positively related to the number of reads in that cell type and the resulting higher statistical power, D1 and D2 MSNs had a markedly lower number of DEGs than other cell types with a similar number of reads (Fig. 2b). Many of the DEGs were differentially expressed in multiple cell