Epistatic Module Detection for Case-Control Studies A Bayesian Model with a Gibbs Sampling Strategy 英文参考文献.docVIP

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Epistatic Module Detection for Case-Control Studies A Bayesian Model with a Gibbs Sampling Strategy 英文参考文献.doc

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Epistatic Module Detection for Case-Control Studies A Bayesian Model with a Gibbs Sampling Strategy 英文参考文献

EpistaticModuleDetectionforCase-ControlStudies:A BayesianModelwithaGibbsSamplingStrategy WanwanTang,XuebingWu,RuiJiang*,YandaLi* MOEKeyLaboratoryofBioinformaticsandBioinformaticsDivision,TNLISTandDepartmentofAutomation,TsinghuaUniversity,Beijing,China Abstract Thedetectionofepistaticinteractiveeffectsofmultiplegeneticvariantsonthesusceptibilityofhumancomplexdiseasesis a great challenge in genome-wide association studies (GWAS). Although methods have been proposed to identify such interactions, the lack of an explicit definition of epistatic effects, together with computational difficulties, makes the developmentofnewmethodsindispensable.Inthispaper,weintroduceepistaticmodulestodescribeepistaticinteractive effectsofmultiplelociondiseases.Onthebasisofthisnotion,weputforwardaBayesianmarkerpartitionmodeltoexplain observed case-control data, and we develop a Gibbs sampling strategy to facilitate the detection of epistatic modules. Comparisonsoftheproposedapproachwiththreeexistingmethodsonsevensimulateddiseasemodelsdemonstratethe superior performance of our approach. When applied to a genome-wide case-control data set for Age-related Macular Degeneration (AMD), the proposed approach successfully identifies two known susceptible loci and suggests that a combinationoftwootherloci—oneinthegeneSGCDandtheotherinSCAPER—isassociatedwiththedisease.Further functionalanalysissupportsthespeculationthattheinteractionofthesetwogeneticvariantsmayberesponsibleforthe susceptibilityofAMD.Whenappliedtoagenome-widecase-controldatasetforParkinson’sdisease,theproposedmethod identifiessevensuspiciouslocithatmaycontributeindependentlytothedisease. Citation: Tang W, Wu X, Jiang R, Li Y (2009) Epistatic Module Detection for Case-Control Studies: A Bayesian Model with a Gibbs Sampling Strategy. PLoS Genet5(5):e1000464.doi:10.1371/journal.pgen.1000464 Editor:NicholasJ.Schork,UniversityofCaliforniaSanDiegoandTheScrippsResearchInstitute,UnitedStatesofAmerica ReceivedOctober17,2008;AcceptedMarch30,2