Aim

The aim of this study was to identify the minimal essential co-expression and physical interaction networks involved in the development of cognition impairment in human mid and late life.

Methods

We searched the Online Mendelian Inheritance in Man (OMIM) database to extract the validated human genes annotated (until March 2020) for five major disorders of pathophysiological overlap and sequential chronological occurrence in human, including multiple sclerosis, type 2 diabetes mellitus, Alzheimer’s disease, vascular dementia, and Lewy body dementia. Gene co-expression and physical interaction networks were subsequently constructed for the overlapping genes across the selected disorders.

Results

Remarkably, each of the gene co-expression and physical interaction networks consisted of single clusters (P = 0.0005 and P = 1 × 10⁻¹⁶, respectively). APP was the major hub in the integrated and tissue-specific co-expression networks, whereas insulin was the major hub in the physical interaction network. Several other hubs were identified across the identified networks, including TNF, VEGFA, GAPDH, and NOTCH1.

Conclusion

We propose the minimal co-expression and physical interaction networks and their single clustering in the development of cognition impairment in human mid and late life. This is a pilot study, warranting identification of more risk genes, using additional validated databases in the future.

中文翻译：

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拟议的最低限度的共同表达和身体互动网络参与了人类中晚期认知障碍的发展。

目标

这项研究的目的是确定参与人类中晚期认知障碍发展的最低限度基本共表达和身体互动网络。

方法

我们搜索了在线孟德尔在线人类遗传（OMIM）数据库，以提取经注释的经验证的人类基因（至2020年3月），以发现人类的五个主要病理生理重叠和顺序发生的疾病，包括多发性硬化症，2型糖尿病，阿尔茨海默氏病，血管性痴呆和路易体痴呆。随后为选定疾病中的重叠基因构建了基因共表达和物理相互作用网络。

结果

值得注意的是，每个基因共表达和物理相互作用网络都由单个簇组成（分别为P  = 0.0005和P  = 1×10 ^-16）。APP是整合的和组织特异性共表达网络中的主要枢纽，而胰岛素是物理相互作用网络中的主要枢纽。在确定的网络中还发现了其他几个集线器，包括TNF，VEGFA，GAPDH和NOTCH1。

结论

我们提出了在人类中晚期认知障碍发展中的最小共表达和身体互动网络及其单一聚类。这是一项试点研究，保证将来可以使用其他经过验证的数据库来识别更多风险基因。