Identification of Risk Pathways and Functional Modules for Coronary Artery Disease Based on Genome-wide SNP Data  

作　　者：Xiang Zhao Yi-Zhao Luan Xiaoyu Zuo Ye-Da Chen Jiheng Qin Lv Jin Yiqing Tan Meihua Lin Naizun Zhang Yan Liang Shao-Qi Rao 

机构地区：[1]Institute for Medical Systems Biology and Department of Medical Statistics and Epidemiology,School of Public Health,Guangdong Medical College,Dongguan 523808,China [2]School of Life Sciences,Sun Yat-sen University,Guangzhou 510080,China [3]Department of Medical Statistics and Epidemiology,School of Public Health,Sun Yat-sen University,Guangzhou 510080,China [4]Maoming People's Hospital,Maoming 525000,China

出　　处：《Genomics, Proteomics & Bioinformatics》2016年第6期349-356,共8页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported in part by the National Natural Science Foundation of China(Grant Nos.31071166 and 81373085);Natural Science Foundation of Guangdong Province,China(Grant No.8251008901000007);Science and Technology Planning Project of Guangdong Province(Grant No.2009A030301004);Dongguan Science and Technology Project,Guangdong,China(Grant No.2011108101015);the funds from Guangdong Medical College,China(Grant Nos.XG1001,JB1214,XZ1105,STIF201122,M2011024,and M2011010)

摘　　要：Coronary artery disease （CAD） is a complex human disease, involving multiple genes and their nonlinear interactions, which often act in a modular fashion. Genome-wide single nucleotide polymorphism （SNP） profiling provides an effective technique to unravel these underlying genetic interplays or their functional involvements for CAD. This study aimed to identify the susceptible pathways and modules for CAD based on SNP omics. First, the Wellcome Trust Case Control Consortium （WTCCC） SNP datasets of CAD and control samples were used to assess the joint effect of multiple genetic variants at the pathway level, using logistic kernel machine regression model. Then, an expanded genetic network was constructed by integrating statistical gene-gene interactions involved in these susceptible pathways with their protein protein interaction （PPI） knowledge. Finally, risk functional modules were identified by decomposition of the network. Of 276 KEGG pathways analyzed, 6 pathways were found to have a significant effect on CAD. Other than glycerolipid metabolism, glycosaminoglycan biosynthesis, and cardiac muscle contraction pathways, three pathways related to other diseases were also revealed, including Alzheimer＇s disease, non-alcoholic fatty liver disease, and Huntington＇s disease. A genetic epistatic network of 95 genes was further constructed using the abovementioned integrative approach. Of 10 functional modules derived from the network, 6 have been annotated to phospholipase C activity and cell adhesion molecule binding, which also have known functional involvement in Alzheimer＇s disease. These findings indicate an overlap of the underlying molecular mechanisms between CAD and Alzheimer＇s disease, thus providing new insights into the molecular basis for CAD and its molecular relationships with other diseases.Coronary artery disease （CAD） is a complex human disease, involving multiple genes and their nonlinear interactions, which often act in a modular fashion. Genome-wide single nucleotide polymorphism （SNP） profiling provides an effective technique to unravel these underlying genetic interplays or their functional involvements for CAD. This study aimed to identify the susceptible pathways and modules for CAD based on SNP omics. First, the Wellcome Trust Case Control Consortium （WTCCC） SNP datasets of CAD and control samples were used to assess the joint effect of multiple genetic variants at the pathway level, using logistic kernel machine regression model. Then, an expanded genetic network was constructed by integrating statistical gene-gene interactions involved in these susceptible pathways with their protein protein interaction （PPI） knowledge. Finally, risk functional modules were identified by decomposition of the network. Of 276 KEGG pathways analyzed, 6 pathways were found to have a significant effect on CAD. Other than glycerolipid metabolism, glycosaminoglycan biosynthesis, and cardiac muscle contraction pathways, three pathways related to other diseases were also revealed, including Alzheimer＇s disease, non-alcoholic fatty liver disease, and Huntington＇s disease. A genetic epistatic network of 95 genes was further constructed using the abovementioned integrative approach. Of 10 functional modules derived from the network, 6 have been annotated to phospholipase C activity and cell adhesion molecule binding, which also have known functional involvement in Alzheimer＇s disease. These findings indicate an overlap of the underlying molecular mechanisms between CAD and Alzheimer＇s disease, thus providing new insights into the molecular basis for CAD and its molecular relationships with other diseases.

关 键 词：Coronary artery disease Genome-wide SNP profiling Risk pathway Functional module Genetic network 

分 类 号：R543.3[医药卫生—心血管疾病]