脑脊液中t-tau蛋白的全基因组网络辅助分析和富集研究

一些基因变异已被发现与阿尔茨海默病典型表型脑脊液相关，但这些发现忽略了小效应风险的变体、基因座内部关联以及与外部环境之间的相互关系.为此，作者利用基于功能网络和基于通路信息的方法从系统生物学角度对遗传变异进行识别.将反映阿尔茨海默症早期病理特点的CSF t-tau作为表型，在全基因组关联分析的基础上提出一种基于权重调整的PageRank网络功能模块挖掘策略.该策略不仅挖掘到广泛研究的与t-tau相关的遗传变异，挖掘到的子网也富集在如神经退行性疾病，神经系统和信号转导等通路中，表明在系统生物学层面，策略识别的特征优先子网与表型具有一定的功能关联.

Genome-Wide Network-Assisted Association and Enrichment Study on CSF t-tau

Some genetic variants have been discovered to associated with cerebrospinal fluid (CSF) in Alzheimer''s disease, yet it does not adapt with the small effect risk variants and ignores the inter-relationship among loci and outer-relationship with environment. As an alternative strategy, functional network-based and pathway-based information could be involved in high-level variants identify process, from system biology view. On the basis of genome-wide association analysis, a weighted-adjusted PageRank network function module mining strategy was proposed to analysis CSF t-tau, which was arranged as a measure reflecting the early pathological characteristics of Alzheimer''s disease. The strategy can not only excavate widely studied t-tau-related genetic variations, but also can excavate subnetworks enriched in pathways, such as neurodegenerative diseases, nervous system and signal transduction. It indicates that, subnetworks identified by the strategy have a certain functional relationship with t-tau at the system biology level.