A Novel Statistic for Genome-Wide Interaction Analysis 英文参考文献.docVIP

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A Novel Statistic for Genome-Wide Interaction Analysis 英文参考文献.doc

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A Novel Statistic for Genome-Wide Interaction Analysis 英文参考文献

ANovelStatisticforGenome-WideInteractionAnalysis XuesenWu1,HuaDong2,LiLuo3,YunZhu3,GangPeng3,JohnD.Reveille4,MomiaoXiong3* 1DepartmentofEpidemiologyandStatistics,BengbuMedicalCollegeatBengbu,Anhui,China,2LaboratoryofTheoreticalSystemsBiologyandCenterforEvolutionary Biology,StateKeyLaboratoryofGeneticEngineering,SchoolofLifeScienceandInstituteforBiomedicalSciences,FudanUniversity,Shanghai,China,3HumanGenetics Center,UniversityofTexasSchoolofPublicHealth,Houston,Texas,UnitedStatesofAmerica, 4DivisionofRheumatology,MedicalSchool,UniversityofTexasHealth ScienceCenteratHouston,Houston,Texas,UnitedStatesofAmerica Abstract Although great progress in genome-wide association studies (GWAS) has been made, the significant SNP associations identifiedbyGWASaccountforonlyafewpercentofthegeneticvariance,leadingmanytoquestionwhereandhowwe can find the missing heritability. There is increasing interest in genome-wide interaction analysis as a possible source of findingheritabilityunexplainedbycurrentGWAS.However,theexistingstatisticsfortestinginteractionhavelowpowerfor genome-wideinteractionanalysis.Tomeetchallengesraisedbygenome-wideinteractionalanalysis,wehavedevelopeda novelstatisticfortestinginteractionbetweentwoloci(eitherlinkedorunlinked).ThenulldistributionandthetypeIerror rates of the new statistic for testing interaction are validated using simulations. Extensive power studies show that the developedstatistichasmuchhigherpowertodetectinteractionthanclassicallogisticregression.Theresultsidentified44 and211pairsofSNPsshowingsignificantevidenceofinteractionswithFDR,0.001and0.001,FDR,0.003,respectively, whichwereseenintwoindependentstudiesofpsoriasis.TheseincludedfiveinteractingpairsofSNPsingenesLST1/NCR3, CXCR5/BCL9L,andGLS2,someofwhichwerelocatedinthetargetsitesofmiR-324-3p,miR-433,andmiR-382,aswellas15 pairsofinteractingSNPsthathadnonsynonymoussubstitutions.Ourresultsdemonstratedthatgenome-wideinteraction analysisisavaluabletoolforfindingremainingmissingheritability