It has been estimated that epilepsies are among the top five neurological diseases with the highest burden of disease. In recent years, genome-wide expression studies (GWES) have been carried out in experimental models of epilepsy and in samples from human patients. In this study, I carried out meta-analyses and analyses of convergence for available GWES for epileptogenesis in humans and in mouse, rat, zebrafish and fruit fly models. Multiple lines of evidence (such as genome-wide association data and known druggable genes) were integrated to prioritize top candidate genes for epileptogenesis and a functional enrichment analysis was carried out. Several top candidate genes, which are supported by multiple lines of genomic evidence, such as GRIN1, KCNAB1 and STX1B, were identified. Druggable genes of potential interest (such as GABRA2, GRIK1, KCNAB1 and STX4) were also identified. An enrichment of genes regulated by the MEF2 and SOX5 transcription factors and the miR-106b-5p and miR-101-3p miRNAs was found. The current work is the first meta-analysis and convergent analysis of GWES for epileptogenesis in humans and in multiple animal models, integrating results from several genomic studies. Novel candidate genes and pathways for epileptogenesis were identified in this analysis.

据估计，癫痫是疾病负担最高的五种神经系统疾病之一。近年来，已经在癫痫实验模型和人类患者样本中进行了全基因组表达研究 (GWES)。在这项研究中，我对人类和小鼠、大鼠、斑马鱼和果蝇模型中用于癫痫发生的可用 GWES 进行了荟萃分析和收敛性分析。整合了多条证据（例如全基因组关联数据和已知的可药用基因）以优先考虑癫痫发生的最佳候选基因，并进行了功能富集分析。几个顶级候选基因，得到多条基因组证据的支持，例如GRIN1、KCNAB1和STX1B, 被识别。还鉴定了潜在感兴趣的可成药基因（例如GABRA2、GRIK1、KCNAB1 和 STX4）。发现受 MEF2 和 SOX5 转录因子以及 miR-106b-5p 和 miR-101-3p miRNA 调节的基因富集。目前的工作是 GWES 在人类和多种动物模型中癫痫发生的首次荟萃分析和收敛分析，整合了多项基因组研究的结果。在该分析中确定了癫痫发生的新候选基因和途径。