RCM: a novel association approach to search for coronary artery disease genetic related metabolites based on SNPs and metabolic network.

Integration of genetic and metabolic network holds promise for providing insight into human disease. Coronary artery disease (CAD) is strongly heritable, but the heritability of metabolic compounds has not been evaluated in human metabolic context. Here we performed a genetic-based computational approach within eight sub-cellular networks from Edinburgh Human Metabolic Network to identify significant genetic risk compounds (SGRCs) of CAD. Our results provide the evidence that the high heritabilities of SGRCs played an important role in CAD pathogenesis. Besides, SGRCs were discovered to be strongly associated with lipid metabolism. We also established a possible disease-causing reference table to decipher genetic associations of SGRCs with CAD. Comparing with traditional method, RCM experienced better performance in CAD genetic risk compounds' identification. These findings provided novel insights into CAD pathogenesis from a genetic perspective.