Enrichment for gene ontology (GO) terms was assessed using GOrilla (Eden et al, 2007; Eden et al, 2009). Refseq genes overlapped by significant DMRs (promoters or introns/exons; n=492) were compared with a background list of Refseq genes (n=11 389) overlapped by all interrogated CpGs. Enrichment of DMR-associated genes for interactions with a list of protein–protein interaction hubs (PPIhubs) was estimated using the Fisher's exact test implemented in the program List2Networks (Lachmann and Ma'ayan, 2010), based on physical protein–protein interaction networks cataloged from several mammalian data sets (Berger et al, 2007); PPIhubs were defined as proteins with >24 known interaction partners (Berger et al, 2007; Lachmann and Ma'ayan, 2010). PPIhub enrichments for DMR-associated genes were compared to those obtained from separate analyses using two gene sets of interest. Rat genome-annotated genes under GO terms ‘regulation of synaptic plasticity' (GO:0048167; n=146) and ‘glutamatergic synaptic transmission' (GO:0035249; n=79) were obtained from the AmiGO 2 database (http://amigo.geneontology.org/amigo). PPI gene network images were generated using genemania (Warde-Farley et al, 2010) based on PPI interactions from databases utilized by Lists2Networks (Berger et al, 2007; Lachmann and Ma'ayan, 2010).
