Department of Neurology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Dementia Institute, Tianjin 300350, China.
Biomed Res Int. 2021 Oct 14;2021:6692974. doi: 10.1155/2021/6692974. eCollection 2021.
Alzheimer's disease (AD) and epilepsy are neurological disorders that affect a large cohort of people worldwide. Although both of the two diseases could be influenced by genetic factors, the shared genetic mechanism underlying the pathogenesis of them is still unclear. In this study, we aimed to identify the shared genetic networks and corresponding hub genes for AD and epilepsy. Firstly, the gene coexpression modules (GCMs) were constructed by weighted gene coexpression network analysis (WGCNA), and 16 GCMs were identified. Through further integration of GCMs, genome-wide association studies (GWASs), and expression quantitative trait loci (eQTLs), 4 shared GCMs of AD and epilepsy were identified. Functional enrichment analysis was performed to analyze the shared biological processes of these GCMs and explore the functional overlaps between these two diseases. The results showed that the genes in shared GCMs were significantly enriched in nervous system-related pathways, such as Alzheimer's disease and neuroactive ligand-receptor interaction pathways. Furthermore, the hub genes of AD- and epilepsy-associated GCMs were captured by weighted key driver analysis (wKDA), including , , , , , , , , and . The shared GCMs and hub genes might provide novel therapeutic targets for AD and epilepsy.
阿尔茨海默病（AD）和癫痫是影响全球大量人群的神经退行性疾病。尽管这两种疾病都可能受到遗传因素的影响，但它们发病机制的共同遗传机制尚不清楚。在这项研究中，我们旨在确定 AD 和癫痫的共享遗传网络和相应的枢纽基因。首先，通过加权基因共表达网络分析（WGCNA）构建基因共表达模块（GCMs），并鉴定出 16 个 GCMs。通过进一步整合 GCMs、全基因组关联研究（GWASs）和表达数量性状基因座（eQTLs），确定了 AD 和癫痫的 4 个共享 GCMs。进行功能富集分析以分析这些 GCMs 的共享生物学过程，并探讨这两种疾病之间的功能重叠。结果表明，共享 GCMs 中的基因显著富集于与神经系统相关的途径，如阿尔茨海默病和神经活性配体-受体相互作用途径。此外，通过加权关键驱动分析（wKDA）捕获了 AD 和癫痫相关 GCMs 的枢纽基因，包括、、、、、、、和。AD 和癫痫相关的共享 GCMs 和枢纽基因可能为 AD 和癫痫提供新的治疗靶点。
