Exploring Candidate Genes for Epilepsy by Computational Disease-Gene Identification Strategy

Epilepsy is a complex disease with a strong genetic component. So far, studies have focused on experimental validation or genome-wide linkage scans for epilepsy susceptibility genes in multiple populations. We have used four bioinformatic tools (SNPs3D, PROSPECTR and SUSPECTS, GenWanderer, PosMed) to analyze 16 susceptibility loci selected from a literature search. Pathways and regulatory network analyses were performed using the Ingenuity Pathways Analysis (IPA) software. We identified a subset of 48 candidate epilepsy susceptibility genes. Five significant canonical pathways, in four typical networks, were identified: GABA receptor signaling, interleukin-6 (IL-6) signaling, G-protein coupled receptor signaling, type 2 diabetes mellitus signaling and airway inflammation in asthma. We concluded that online analytical tools provide a powerful way to reveal candidate genes which can greatly reduce experimental time. Our study contributes to further experimental tests for epilepsy susceptibility genes.