Network Properties of Complex Human Disease Genes Identified through Genome-Wide Association Studies 英文参考文献.docVIP

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Network Properties of Complex Human Disease Genes Identified through Genome-Wide Association Studies 英文参考文献.doc

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Network Properties of Complex Human Disease Genes Identified through Genome-Wide Association Studies 英文参考文献

NetworkPropertiesofComplexHumanDiseaseGenes IdentifiedthroughGenome-WideAssociationStudies FredrikBarrenas1.*,SreenivasChavali1.,PetterHolme2,3,RezaMobini1,MikaelBenson1 1The Unit for Clinical Systems Biology, University of Gothenburg, Gothenburg, Sweden, 2Department of Physics, Umea? University, Umea?, Sweden, 3Department of EnergyScience,SungkyunkwanUniversity,Suwon,Korea Abstract Background:Previousstudiesofnetworkpropertiesofhumandiseasegeneshavemainlyfocusedonmonogenicdiseases orcancersandhavesufferedfromdiscoverybias.Hereweinvestigatedthenetworkpropertiesofcomplexdiseasegenes identifiedbygenome-wideassociationstudies(GWAs),therebyeliminatingdiscoverybias. Principalfindings:Wederivedanetworkofcomplexdiseases(n=54)andcomplexdiseasegenes(n=349)toexplorethe shared genetic architecture of complex diseases. We evaluated the centrality measures of complex disease genes in comparisonwithessentialandmonogenicdiseasegenesinthehumaninteractome.Thecomplexdiseasenetworkshowed thatdiseasesbelongingtothesamediseaseclassdonotalwayssharecommondiseasegenes.Apossibleexplanationcould bethatthevariantswithhigherminorallelefrequencyandlargereffectsizeidentifiedusingGWAsconstitutedisjointparts oftheallelicspectraofsimilarcomplexdiseases.Thecomplexdiseasegenenetworkshowedhighmodularitywiththesize ofthelargestcomponentbeingsmallerthanexpectedfromarandomizednull-model.Thisisconsistentwithlimitedsharing ofgenesbetweendiseases.Complexdiseasegenesarelesscentralthantheessentialandmonogenicdiseasegenesinthe humaninteractome.Genesassociatedwiththesamedisease,comparedtogenesassociatedwithdifferentdiseases,more oftentendtoshareaprotein-proteininteractionandaGeneOntologyBiologicalProcess. Conclusions: This indicates that network neighbors of known disease genes form an important class of candidates for identifyingnovelgenesforthesamedisease. Citation:BarrenasF,ChavaliS,HolmeP,MobiniR,BensonM(2009)NetworkPropertiesofComplexHumanDiseaseGenesIdentifiedthroughGenome-Wide AssociationStudies.PLoSON