Department of Neurology, Fujian Medical University Union Hospital, Fuzhou 350001, China.
Intensive Care Unit, Department of Neurology, Fujian Medical University Union Hospital, Fuzhou 350001, China.
Comput Intell Neurosci. 2022 Apr 12;2022:6799285. doi: 10.1155/2022/6799285. eCollection 2022.
Current epidemiological and experimental studies have indicated the overlapping genetic foundation of epilepsy and depression. However, the detailed pleiotropic genetic etiology and neurobiological pathways have not been well understood, and there are many variants with underestimated effect on the comorbidity of the two diseases. Utilizing genome-wide association study (GWAS) summary statistics of epilepsy (15,212 cases and 29,677 controls) and depression (170,756 cases and 329,443 controls) from large consortia, we assessed the integrated gene-based association with both diseases by Multimarker Analysis of Genomic Annotation (MAGMA) and Fisher's meta-analysis. On the one hand, shared genes with significantly altered transcripts in Gene Expression Omnibus (GEO) data sets were considered as possible pleiotropic genes. On the other hand, the pathway enrichment analysis was conducted based on the gene lists with nominal significance in the gene-based association test of each disease. We identified a total of two pleiotropic genes ( and ) with gene expression analysis validated and interpreted twenty-five common biological process supported with literature mining. This study indicates the potentially shared genes associated with both epilepsy and depression based on gene expression, meta-data analysis, and pathway enrichment strategy along with traditional GWAS and provides insights into the possible intersecting pathways that were not previously reported.
目前的流行病学和实验研究表明，癫痫和抑郁症有重叠的遗传基础。然而，详细的多效遗传病因和神经生物学途径尚未得到很好的理解，而且有许多对这两种疾病共病影响被低估的变异。我们利用来自大型联盟的癫痫（15212 例病例和 29677 例对照）和抑郁症（170756 例病例和 329443 例对照）的全基因组关联研究（GWAS）汇总统计数据，通过多标记基因组注释分析（MAGMA）和 Fisher 荟萃分析评估了两种疾病的综合基因关联。一方面，考虑到基因表达谱数据库（GEO）中具有显著改变转录本的共享基因可能是多效基因。另一方面，根据每种疾病的基因关联测试中具有名义意义的基因列表进行了通路富集分析。我们总共确定了两个多效基因（和），并通过基因表达分析进行了验证和解释，通过文献挖掘支持了二十五个常见的生物学过程。这项研究基于基因表达、元数据分析和通路富集策略，以及传统的 GWAS，确定了与癫痫和抑郁症相关的潜在共享基因，为以前未报道的可能的交叉途径提供了新的见解。
