A Novel Evolution-Based Method for Detecting Gene-Gene Interactions 英文参考文献.docVIP

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A Novel Evolution-Based Method for Detecting Gene-Gene Interactions 英文参考文献.doc

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A Novel Evolution-Based Method for Detecting Gene-Gene Interactions 英文参考文献

ANovelEvolution-BasedMethodforDetectingGene- GeneInteractions ShaoqiRao1,2,3*,ManqiongYuan2,XiaoyuZuo3,WeiyangSu3,FanZhang3,KeHuang4,MeihuaLin1, YuanlinDing1 1DepartmentofMedicalStatisticsandEpidemiology,SchoolofPublicHealth,GuangdongMedicalCollege,Dongguan,Guangdong,China,2DepartmentofStatistical Sciences, School of Mathematics and Computational Science, Sun Yat-Sen University, Guangzhou, Guangdong, China, 3Department of Medical Statistics and Epidemiology,SchoolofPublicHealth,SunYat-SenUniversity,Guangzhou,Guangdong,China,4InstituteofBloodTransfusion,GuangzhouBloodCenter,Guangzhou, Guangdong,China Abstract Background:Therapidadvanceinlarge-scaleSNP-chiptechnologiesoffersusgreatopportunitiesinelucidatingthegenetic basisofcomplexdiseases.Methodsforlarge-scaleinteractionsanalysishavebeenunderdevelopmentfromseveralsources. Due to several difficult issues (e.g., sparseness of data in high dimensions and low replication or validation rate), developmentoffast,powerfulandrobustmethodsfordetectingvariousformsofgene-geneinteractionscontinuestobea challengingtask. Methodology/PrincipalFindings:Inthisarticle,wehavedevelopedanevolution-basedmethodtosearchforgenome-wide epistasisinacase-controldesign.Fromanevolutionaryperspective,weviewthathumandiseasesoriginatefromancient mutationsandconsiderthattheunderlyinggeneticvariantsplayaroleindifferentiatinghumanpopulationintothehealthy andthediseased.Basedonthisconcept,traditionalevolutionarymeasure,fixationindex(Fst)fortwounlinkedloci,which measuresthegeneticdistancebetweenpopulations,shouldbeabletorevealtheresponsiblegeneticinterplaysfordisease traits.Tovalidateourproposal,wefirstinvestigatedthetheoreticaldistributionofFstbyusingextensivesimulations.Then, we explored its power for detecting gene-gene interactions via SNP markers, and compared it with the conventional PearsonChi-squaretest,mutualinformationbasedtestandlinkagedisequilibriumbasedtestunderseveraldiseasemodels. The proposed evolution-based method outperformed these com