Pathway enrichment analysis of the thistle2 module showed a significant downregulation of pathways related to calcium signaling (Fig. 3a). Gene-ontology enrichment analysis using the clusterpProfiler showed significant enrichment for biological processes involved in “response to nicotine” and “excitatory postsynaptic potential” (Fig. 3b). Several genes in the thistle2 module that were significantly downregulated in the PFC of alcohol-dependent subjects. Differentially expressed genes in the thistle2 module mapped to networks involved in G-protein coupled receptor signaling, calcium signaling, and opioid signaling (Fig. 3c). Cholinergic Receptor Nicotinic Alpha subunits 6 and 2 (CHRNA6 UKBB-AC P = 7.60 × 10−3; CHRNA2 PGC-AD P = 1.4 × 10−2), Meningioma 1 (MN1, PGC-AD P = 9.1 × 10−3) and Hyaluronan And Proteoglycan Link Protein 1 (HAPLN1, UKBB-AC P = 1.9 × 10−2) are some exmples where differntialy expressed genes in thistle 2 module also showed some evidence of genetic contribution towards alcohol consumption or dependence.
