multistage sampling for disease family registries

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1、MultistageSamplingforDiseaseFamilyRegistriesKimberlyD.Siegmund,AliceS.Whittemore,DuncanC.ThomasdesignforstudyingtheassociationbetweenararediseaseandaBackground:Theobjectivesofafamily-baseddiseaseregis-rareexposure.Sincethen,therehasbeenanabundanceofrelatedtryrangefromcharacterizingme

2、asuredgeneticfactorsandworkbyothers(6±11).Anelementarytwo-stagedesignisthegene±environmentinteractioneffectstodetectingnovelsus-following.Inthefirststage,oneselectsarandomsampleofcaseceptibilitygenes.Gatheringcompleteinformationonexpo-patientsandcontrolsubjectsandassessesexposureonal

3、lofsureanddiseasestatusinallfamilymembersforasampleofthem;inthesecondstage,oneconductsasubsamplefromthe2affectedsubjects(probands)toaddressthesediverseobjec-×2tableofexposedandunexposedcasepatientsandcontroltiveswouldbeprohibitivelyexpensive.Methods:Multistagesubjectsandcollectsaddit

4、ionalcovariateinformationonlyonsamplingcanbeusedtodesignanefficientfamily-basedthesesampledindividuals.Alternatively,onemightobtainadiseaseregistry.Ateachstage,theprobandsareclassifiedonsurrogateforexposureonallparticipantsinthefirststageasthethebasisofpreviouslycollecteddata,andasub

5、sampleisbasisforstratificationandthenobtainmorepreciseexposureselectedformoredetailedobservation.Thedesigncanbedataonlyonparticipantsinthesecondstage.Thelatterispar-optimizedtominimizethevarianceofanyofthemodelpa-ticularlyrelevantinthegeneticcontextinwhichfamilyhistoryrameterestimate

6、s,subjecttoaconstraintonthetotalsampleisanaturalsurrogatetoconsiderforthegenotypesthatmightbemeasuredinlaterstagesbutwouldbetooexpensivetoobtainforDownloadedfromsize.Results:Wedescribethebasicstatisticaltheoryanditsapplicationtoafour-stagesamplingschemeproposedfortheallparticipants.C

7、ooperativeFamilyRegistryforEpidemiologicStudiesofWhittemoreandHalpern(12)havediscussedtheapplicationColorectalCancerattheUniversityofSouthernCalifornia.ofmultistagesamplingtothefieldofgeneticepidemiology.As[MonogrNatlCancerInst1999;26:43±8]oneexample,theydescribedasamplingdesignforas

8、tudyofprosta