A General Model for Multilocus Epistatic Interactions in Case-Control Studies 英文参考文献.docVIP

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A General Model for Multilocus Epistatic Interactions in Case-Control Studies 英文参考文献.doc

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A General Model for Multilocus Epistatic Interactions in Case-Control Studies 英文参考文献

AGeneralModelforMultilocusEpistaticInteractionsin Case-ControlStudies ZhongWang1,2,TianLiu3,ZhenwuLin4,JohnHegarty4,WalterA.Koltun4,RonglingWu1,2* 1CenterforStatisticalGenetics,PennsylvaniaStateUniversity,Hershey,Pennsylvania,UnitedStatesofAmerica,2PennsylvaniaStateCancerInstitute,PennsylvaniaState University,Hershey,Pennsylvania,UnitedStatesofAmerica,3HumanGeneticsGroup,GenomeInstituteofSingapore,Singapore,Singapore,4DepartmentofSurgery, PennsylvaniaStateUniversity,Hershey,Pennsylvania,UnitedStatesofAmerica Abstract Background:Epistasis,i.e.,theinteractionofallelesatdifferentloci,isthoughttoplayacentralroleintheformationand progressionofcomplexdiseases.Thecomplexityofdiseaseexpressionshouldarisefromacomplexnetworkofepistatic interactionsinvolvingmultiplegenes. Methodology:Wedevelopageneralmodelfortestinghigh-orderepistaticinteractionsforacomplexdiseaseinacase- controlstudy.Weincorporatethequantitativegenetictheoryofhigh-orderepistasisintothesettingofcasesandcontrols sampledfromanaturalpopulation.Thenewmodelallowstheidentificationandtestingofepistasisanditsvariousgenetic components. Conclusions: Simulation studies were used to examine the power and false positive rates of the model under different samplingstrategies.Themodelwasusedtodetectepistasisinacase-controlstudyofinflammatoryboweldisease,inwhich fiveSNPsatacandidategeneweretyped,leadingtotheidentificationofasignificantthree-locusepistasis. Citation:WangZ,LiuT,LinZ,HegartyJ,KoltunWA,etal.(2010)AGeneralModelforMultilocusEpistaticInteractionsinCase-ControlStudies.PLoSONE5(8): e11384.doi:10.1371/journal.pone.0011384 Editor:ZviaAgur,InstituteforMedicalBiomathematics,Israel ReceivedJanuary15,2010;AcceptedMay31,2010;PublishedAugust18,2010 Copyright: ? 2010 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkissupportedbyN