Background

Major depressive disorder (MDD) and type 2 diabetes mellitus (T2DM) are common public health disorders that often co-occur. This study aims to determine whether gene expression profiles from individuals with MDD or T2DM overlap and if there are any functional interconnectivity between identified genes using protein-protein interaction (PPI).

Methods

The DNA microarray datasets were extracted from the Gene Expression Omnibus. Gene expression dataset GSE98793 from a case-control study of MDD (64 healthy control subjects, 128 patients) and dataset GSE15653 from a case-control study of T2DM (nine controls, nine individuals with T2DM) were used for this secondary and post-hoc analysis. GO enrichment analyses and Reactome pathway enrichment analysis were performed for functional enrichment analyses with the shared genes. PPI networks, PPI clusters and hub genes were performed to detect the potential relationships among differentially expressed genes (DEG) -encoding proteins in both MDD and T2DM.

Results

A total of 3640 DEGs were identified in the MDD group when compared to the control group, whereas 3700 DEGs were identified in the T2DM group when compared to the control groups, among which 244 DEGs were overlap genes. The identified DEGs were enriched for Interleukin-4 and Interleukin-13 signaling, neutrophil degranulation, as well as other select species of the innate immune system. The biological processes of neurofibrillary tangle assembly regulation, tau-protein kinase activity regulation, amyloid-beta clearance regulation, amyloid-beta formation regulation and neuron apoptotic processes were also identified. Molecular function analysis indicated that identified genes were mainly enriched for amyloid-beta binding. 925 out of 1006 protein-protein interactions and six sub-networks were identified reflecting the disparate biological domains of overlapping genes. Ten hub genes further highlight the putative importance of tau-protein kinase activity, inflammatory response and neuron apoptotic regulatory processes across MDD and T2DM.

Conclusions

Our results indicate that an overlapping genetic architecture subserves MDD and T2DM. Genes relevant to the innate immune system, tau protein formation, and cellular aging were identified. Results indicate that the common, often comorbid, conditions of MDD and T2DM have a pathoetiologic nexus.

中文翻译：

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重度抑郁症和 2 型糖尿病之间的遗传关联：共享通路和蛋白质网络

背景

重度抑郁症 (MDD) 和 2 型糖尿病 (T2DM) 是共同发生的常见公共卫生疾病。本研究旨在确定 MDD 或 T2DM 个体的基因表达谱是否重叠，以及使用蛋白质-蛋白质相互作用 (PPI) 确定的基因之间是否存在任何功能互连。

方法

DNA 微阵列数据集是从 Gene Expression Omnibus 中提取的。来自 MDD 病例对照研究（64 名健康对照受试者，128 名患者）的基因表达数据集 GSE98793 和来自 T2DM 病例对照研究（9 名对照，9 名患有 T2DM 的个体）的数据集 GSE15653 用于该次要和事后分析。GO富集分析和Reactome通路富集分析用于共享基因的功能富集分析。进行 PPI 网络、PPI 簇和中枢基因以检测 MDD 和 T2DM 中差异表达基因 (DEG) 编码蛋白之间的潜在关系。

结果

与对照组相比，MDD组共鉴定出3640个DEG，而与对照组相比，T2DM组鉴定出3700个DEG，其中244个DEG为重叠基因。鉴定出的 DEG 富含白细胞介素 4 和白细胞介素 13 信号传导、中性粒细胞脱粒以及其他先天免疫系统的选择物种。还确定了神经原纤维缠结组装调节、tau 蛋白激酶活性调节、β-淀粉样蛋白清除调节、β-淀粉样蛋白形成调节和神经元凋亡过程的生物学过程。分子功能分析表明，鉴定的基因主要富集淀粉样蛋白-β 结合。确定了 1006 个蛋白质-蛋白质相互作用中的 925 个和六个子网络，反映了重叠基因的不同生物学域。十个中心基因进一步强调了 MDD 和 T2DM 中 tau 蛋白激酶活性、炎症反应和神经元凋亡调节过程的假定重要性。

结论

我们的结果表明，重叠的遗传结构支持 MDD 和 T2DM。鉴定了与先天免疫系统、tau 蛋白形成和细胞衰老相关的基因。结果表明，MDD 和 T2DM 的常见且经常合并的病症具有病理关系。