Analysis of PFC tissue derived from 65 alcoholics and 73 controls identified 827 differentially expressed genes at 25% FDR, 298 genes at 10% FDR and 129 genes at 5% FDR (Fig. 1a, Supplemental Table 1; protein coding genes only). Transient Receptor Potential Cation Channel Subfamily C Member 3 (TRPC3) was the top differentially expressed gene with significantly lower expression in alcohol-dependent subjects (FC 0.82; p = 4.6 × 10−9), while Kinesin Family Member 19 (KFM19) showed significantly higher expression in alcohol-dependent subjects (FC 1.24; p = 5.7 × 10−9). IPA analysis of the differentially expressed genes (FDR < 25%) showed significant enrichment for pathways involved in interferon signaling, GADD45 signaling, and other immune-related pathways (Fig. 1b). Gene-ontology enrichment analysis using clusteProfiler mapped a large proportion of genes to biological processes involved in blood coagulation and fluid transport (Fig. 1c). The network analysis in IPA mapped the significant genes to networks involved in neurodegenerative disorders and organismal injury. Several genes that were part of this network were also nominally significant (p < 0.05) in the PGC-AD and UKBB-AC GWAS (Fig. 1d).
