Interactome overlap between risk genes of epilepsy and targets of anti-epileptic drugs

Anti-epileptic drugs have been used for treating epilepsy for decades, meanwhile, more than one hundred genes have been identified to be associated with risk of epilepsy; however, the interaction mechanism between anti-epileptic drugs and risk genes of epilepsy was still not clearly understood. In this study, we systematically explored the interaction of epilepsy risk genes and anti-epileptic drug targets through a network-based approach. Our results revealed that anti-epileptic drug targets were significantly over-represented in risk genes of epilepsy with 17 overlapping genes and P-value = 2.2 x 10(-16). We identified a significantly localized PPI network with 55 epileptic risk genes and 94 anti-epileptic drug target genes, and network overlap analysis showed significant interactome overlap between risk genes and drug targets with P-value = 0.04. Besides, genes from PPI network were significantly enriched in the co-expression network of epilepsy with 22 enriched genes and P-value = 1.3 x 10(-15) ; meanwhile, cell type enrichment analysis indicated genes in this network were significantly enriched in 4 brain cell types (Interneuron, Medium Spiny Neuron, CA1 pyramidal Neuron, and Somatosensory pyramidal Neuron). These results provide evidence for significant interactions between epilepsy risk genes and anti-epileptic drug targets from the perspective of network biology.