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1、Genetics:AdvanceOnlinePublication,publishedonSeptember28,2012as10.1534/genetics.112.144790LocalancestrycorrectsforpopulationstructureinS.cerevisiaegenome-wideassociationstudiesLiyangDiaoandKevinC.ChenBioMaPSInstituteforQuantitativeBiologyandDepartmentofGeneticsRutgers,TheStateUniversityof
2、NewJerseyPiscataway,NJ08854,USA1Copyright2012.Runningtitle:ComparingGWASMethodsinYeastKeywords:Genome-wideassociationstudies,Saccharomycescerevisiae,mixedlinearmodel,populationstructure,localancestryCorrespondingauthor:KevinC.ChenRutgers,TheStateUniversityofNewJerseyDept.ofGeneticsandBioM
3、aPSInst.forQuantitativeBiology145BevierRoadPiscataway,NJ08854,USAPhone:7324451027ext40055Fax:7324451147kcchen@biology.rutgers.edu2ABSTRACTGenome-wideassociationstudies(GWAS)havebecomeanimportantmethodformappingthegeneticlociunderlyingcomplexphenotypictraitsinmanyspecies.Acrucialissuewhenp
4、erformingGWASistocontrolfortheunderlyingpopulationstructure,sincethiscanleadtospuriousassociations.Populationstructureisaparticularlyimportantissueinnon-humanspeciessinceitisoftendifficulttocontrolforpopulationstructureduringthestudydesignphase,sopopulationstructuremustbecorrectedstatisti
5、callyafterthedatahasbeencollected.IthasnotyetbeenestablishedifGWASisafeasibleapproachinSaccharomycescerevisiae,animportantmodelorganismandagriculturalspecies.WethusperformedanempiricalstudyofstatisticalmethodsforcontrollingforpopulationstructureinGWASusingasetof201phenotypictraitsmeasured
6、inmultipleresequencedstrainsofS.cerevisiae.Wecomplementedouranalysisofrealdatawithanextensivesetofsimulations.Ourmainresultisthatamixedlinearmodelusingthelocalancestryofthestrainasacovariateiseffectiveatcontrollingforpopulationstructure,consistentwiththemosaicstructureofmanyS.cerevisiaest
7、rains.WefurtherstudiedtheevolutionaryforcesactingontheGWASSNPsandfoundthatSNPsassociatedwithvariationinphenotypictraitsareenrichedforlowminorallelefrequencies,consistentwiththeactionofnegativeselectionontheseSNPs.Despitetheeffectivenessoflocalancestrycorrection,GWAS
