整合冠心病风险SNPs功能及分子网络特征筛选疾病易感基因

Integrating Functional Information of Risk SNPs and the Molecular Network Characteristics to Screen Disease Susceptibility Genes

目的:冠心病(Coronary Heart Disease,CHD)是一种由多因素(遗传因素、环境因素以及它们之间的相互作用)引起的复杂疾病。本文从遗传因素和分子互作模式识别新的冠心病易感基因。方法:结合冠心病群体遗传SNPs数据和PPI数据,通过群体遗传数据的风险评估、功能SNPs的判定和PPI网络基因的分类,以功能SNPs属性、网络拓扑属性和基因功能属性为特征,利用两步分类的方法筛选新的冠心病易感基因。结果:获得了69个新的冠心病易感基因,其中43个被文献证实与冠心病的发生发展密切相关,且识别的新的易感基因注释的KEGG通路中有很多是已知的易感基因所没有注释到的,如MAPK signaling pathway,Calcium signaling pathway,Focal adhesion和Chemokine signaling pathway等,其中Chemokine signaling pathway被证实是CHD发展的关键通路。结论:应用本文提出的整合筛选策略,能识别与冠心病相关的新的易感基因,可为冠心病的预防、诊断和治疗提供新的研究方向。

Objective： Coronary heart disease（CHD） is a complex disease caused by many factors（genetic factors, environmental factors and the interactions between them）. New coronary heart disease susceptibility genes were recognized from the perspective of genetic factors and molecular interaction patterns in this paper. Methods： The population genetic SNPs of CHD and protein-protein interaction data were combined, the risks of population genetic SNPs were assessed, function SNPs were determined and genes in a PPI network were classified. New CHD susceptibility genes were screened out using the method of two-step classification with function SNP attributes,network topological attributes and gene function attributes as classification features. Results： 69 new CHD susceptibility genes were obtained, and 43 of them were confirmed to be closely related to the development of CHD. Many KEGG pathways annotated by new susceptibility genes could not be annotated by known susceptibility genes, such as MAPK signaling pathway, Calcium signaling pathway,Focal adhesion, Chemokine signaling pathway, and so on. Chemokine signaling pathway has been proved to be the critical pathway for the development of CHD. Conclusion： The integrated screening strategy proposed in this paper could identify new susceptibility genes associated with CHD, and provide a new direction for the prevention, diagnosis and treatment of CHD.