Information about gene interactions comes from seven interaction databases including IntAct [57], BIND [58], HPRD [59], BioGRID [8], HiMAP, DIP and STRING [60]. We annotated all addiction susceptibility genes using these data. 10,000 Monte Carlo simulations were performed to estimate the distribution for testing the enrichment for interactions between addiction susceptibility genes and addiction-related genes identified by molecular biology studies, in which addiction susceptibility gene lists were randomly created from human genome, followed by the identical analyses pipelines for gene interaction annotations and calculations. Monte Carlo p-values < 0.05 were considered to be a sign for interaction enrichment between the two datasets to a statistically significant degree. We performed functional enrichment test for addiction susceptibility genes using KOBAS [61] and DAVID [62], following published protocols [21]. Functional categories with p-values < 0.05 were considered enriched in addiction susceptibility genes to a statistically significant degree.
