The six mRNA modules significantly correlated with AD were explored to identify hub genes. In scale-free network topology, ‘hubs’ are the most highly connected genes (of which there are relatively few among all the nodes within a network). A highly significant positive correlation between module membership ((MM), correlation of individual gene expression with ME of its respective module) and gene significance ((GS), correlation of individual gene expression with AD case-status) for NAc was observed, supporting previous observations in PFC, where genes significantly correlated with AD were also the most important (or central) elements of the module for AD (Fig 3A) [42]. Of the 2034 transcripts clustered in the six modules, 518 transcripts were located in the top quartile of MM and were selected as candidate hub transcripts (see Material and Methods). After collapsing their transcript IDs to unique Hugo Gene Nomenclature (HGNC) symbols, 461 unique genes were identified. Among these, three genes, guanylate cyclase activator 1A (GUCA1A), polypyrimidine tract binding protein 1 (PTBP1), and transgelin 2 (TAGLN2) were shared as hub genes in more than one module. Full transcript, GS, MM, and gene symbol annotation for candidate hub transcripts are available in S3 Table.
