中国科学院昆明动物研究所机构知识库

Schizophrenia (SCZ) is a complex mental disorder with high heritability. Genetic studies (especially recent ge-nome-wide association studies) have identified many risk genes for schizophrenia. However, the physical inter-actions among the proteins encoded byschizophreniariskgenes remain elusiveand itisnotknown whethertheidentifiedriskgenesconvergeoncommonmolecularnetworksorpathways.Herewesystematicallyinvestigatedthe network characteristics of schizophrenia risk genes using the high-confidence protein-protein interactions(PPI) from the human interactome. We found that schizophrenia risk genes encode a densely interconnectedPPI network (P = 4.15 × 10 −31 ). Compared with the background genes, the schizophrenia risk genes in the in-teractome have significantly higher degree (P = 5.39 × 10 −11 ), closeness centrality (P = 7.56 × 10 −11 ),betweeness centrality (P = 1.29 × 10 −11 ), clusteringcoefficient (P = 2.22 × 10 −2 ), and shorter average shortestpath length (P = 7.56 × 10 −11 ). Based on the densely interconnected PPI network, we identified 48 hub genesand 4 modules formed by highly interconnected schizophrenia genes. We showed that the proteins encodedbyschizophrenia hubgenes have significantlymoredirect physicalinteractions. Geneontology(GO)analysisre-vealed that cell adhesion, cell cycle, immune system response, and GABR-receptor complex categories wereenriched in the modules formed by highly interconnected schizophrenia risk genes. Our study reveals thatschizophreniariskgenesencodeadenselyinterconnectedmolecularnetworkanddemonstratesthemodularna-ture of schizophrenia.