Gene-environment-wide association studies_emerging approaches

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1、REVIEWSGenome-wideassociationstudiesGene–environment-wideassociationstudies:emergingapproachesDuncanThomasAbstract

2、Despitetheyieldofrecentgenome-wideassociation(GWA)studies,theidentifiedvariantsexplainonlyasmallproportionoftheheritabilityofmostcomplexdiseases.Thisunexplainedheritabilitycouldbepart

3、lyduetogene–environment(G×E)interactionsormorecomplexpathwaysinvolvingmultiplegenesandexposures.ThisReviewprovidesatutorialontheavailableepidemiologicaldesignsandstatisticalanalysisapproachesforstudyingspecificG×Einteractionsandchoosingthemostappropriatemethods.Idiscusstheapproachesthatarebeingdev

4、elopedforstudyingentirepathwaysandavailabletechniquesformininginteractionsinGWAdata.Ialsoexploremethodsformarryinghypothesis-drivenpathway-basedapproacheswith‘agnostic’GWAstudies.Theterm‘interaction’hasvariousmeaningsintheofG×EinteractionsinriskpredictionmodelscanhaveMarginaleffectsTheeffectsofasp

5、ecificriskepidemiologicliterature,dependingonthecontext(BOX1).importantimplicationsforbothpublichealthandfactor(geneorexposure)ThefocusofthisReviewisongene–environment(G×E)personalizedmedicine7.inthepopulationasainteraction,heredefinedasajointeffectofoneormoreTraditionally,G×Einteractionswereinves

6、tigatedwhole,averagingoverallgeneswithoneormoreenvironmentalfactorsthatcan-usingcandidate-genestudies.Thisresearchoftenbeginsothervariables.notbereadilyexplainedbytheirseparatemarginaleffects.withanestablishedassociationwithanenvironmentalGenome-wideassociationByconventioninepidemiology,amultiplic

7、ativemodelfactorandproceedstoexploregenesinpathwaysthatarestudyistakenasthenullhypothesis;thatis,therelativeriskofknowntometabolizethem.Overtime,candidate-geneAscanoftheentiregenomefordiseaseinindividualswithboththegeneticandenvi-studieshavebecomemoreelaborateinvestigationsofassociationwithadiseas

8、eorronmentalriskfactorsistheproductoftherelativerisksentirepathways,includingallofthegenes,exposuresandtraitusingastandardpanelof~500,000to1millionofeachseparately.Therefore,anyjointeffectthatdifferscofactorsthat