network properties of complex human disease genes identified through genome-wide association studies网络属性复杂的人类疾病基因通过全基因组关联研究确定.pdfVIP

Network Properties of Complex Human Disease Genes Identified through Genome-Wide Association Studies 1. 1. 2,3 1 1 Fredrik Barrenas *, Sreenivas Chavali , Petter Holme , Reza Mobini , Mikael Benson ˚ ˚ 1The Unit for Clinical Systems Biology, University of Gothenburg, Gothenburg, Sweden, 2 Department of Physics, Umea University, Umea, Sweden, 3 Department of Energy Science, Sungkyunkwan University, Suwon, Korea Abstract Background: Previous studies of network properties of human disease genes have mainly focused on monogenic diseases or cancers and have suffered from discovery bias. Here we investigated the network properties of complex disease genes identified by genome-wide association studies (GWAs), thereby eliminating discovery bias. Principal findings: We derived a network of complex diseases (n = 54) and complex disease genes (n = 349) to explore the shared genetic architecture of complex diseases. We evaluated the centrality measures of complex disease genes in comparison with essential and monogenic disease genes in the human interactome. The complex disease network showed that diseases belonging to the same disease class do not always share common disease genes. A possible explanation could be that the variants with higher minor allele frequency and larger effect size identified using GWAs constitute disjoint parts of the allelic spectra of similar complex diseases. The complex disease gene network showed high modularity with the size of the largest component being smaller than expected from a randomized null-model. This is consistent with limited sharing