Application of Ancestry Informative Markers to Association Studies in European Americans 英文参考文献.docVIP

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Application of Ancestry Informative Markers to Association Studies in European Americans 英文参考文献.doc

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Application of Ancestry Informative Markers to Association Studies in European Americans 英文参考文献

Perspective ApplicationofAncestryInformativeMarkers toAssociationStudiesinEuropean Americans Michael F.Seldin*,Alkes L.Price* R ecently,wholegenomeassociation(WGA)studies haveacceleratedprogressinthesearchforgenetic variationsunderlyingtheinheritanceofcomplex geneticdiseases.Althoughpopulationdifferencesinallele frequenciesareusuallysmall,thesestudieshave thecountry,wouldbewell-advisedtode?neancestrytothe fullestextentpossible.Ontheotherhand,astudyofa phenotypewithnoknownancestrydifferences,involving casesandcontrolsrigorouslymatchedbylocation,might choosetobypasstheuseofAIMsentirely.Anintermediate optionwouldbetomodelonlynorth–southancestry, addressingthesinglemostlikelysourceofstrati?cationat partialcost,withsomeresidualriskofstrati?cation. demonstratedtheimportanceofaccountingforpopulation differencesinordertoreducefalsepositiveassociations.Even withinacontinentalpopulation,populationstrati?cation— ancestrydifferencesbetweencasesandcontrols—cancause falseassociationsatmarkerswhosefrequencydiffersacross subpopulations[1,2].Forexample,inarecentWGAstudyof rheumatoidarthritisinEuropeanAmericans,markersinthe LCTandIRF4geneswouldhavebeenfalselyimplicatedas associatedtodiseasewithouttheapplicationofmethodsto controlforstrati?cation[3].Similarempiricalexamplesof populationstrati?cationexistforotherphenotypes,and geneticriskhasbeenreportedtovaryacrossEuropefora widerangeofdiseases[4–8].Ingeneral,investigatorsshould bealertedtoconsiderpopulationstrati?cationwhenWGA dataindicatesthataparticularmarkershowsastrong frequencygradientacrossEurope. Methodshavealreadybeendevelopedtocontrolfor populationstrati?cationintheinitialstageofWGAstudies, inwhichdatafromhundredsofthousandsofmarkersis generated[9,10].However,controllingforstrati?cationisjust asimportantinreplicationstudiesinindependentsample sets,whichwillfocusonasmallnumberofmarkers.Similarly, candidategenestudiesand?nemappingorsequencing studieswillalsorequireattentiontopopulationdifferences. Becauseasmallnumberofcandid