Family-Based versus Unrelated Case-Control Designs for Genetic Associations 英文参考文献.docVIP

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Family-Based versus Unrelated Case-Control Designs for Genetic Associations 英文参考文献.doc

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Family-Based versus Unrelated Case-Control Designs for Genetic Associations 英文参考文献

Family-BasedversusUnrelatedCase-Control DesignsforGeneticAssociations Evangelos Evangelou1,Thomas A.Trikalinos1,2,Georgia Salanti3,John P.A.Ioannidis1,2,4* 1DepartmentofHygieneandEpidemiology,UniversityofIoanninaSchoolofMedicine,Ioannina,Greece,2InstituteforClinicalResearchandHealthPolicyStudies,Tufts UniversitySchoolofMedicine,Boston,Massachusetts,UnitedStatesofAmerica,3BiostatisticsUnit,MedicalResearchCouncil,Cambridge,UnitedKingdom,4Biomedical ResearchInstitute,FoundationforResearchandTechnology-Hellas,Ioannina,Greece Themostsimpleandcommonlyusedapproachforgeneticassociationsisthecase-controlstudydesignofunrelated people.Thisdesignissusceptibletopopulationstratification.Thisproblemisobviatedinfamily-basedstudies,butitis usuallydifficulttoaccumulatelargeenoughsamplesofwell-characterizedfamilies.Weaddressedempiricallywhether the two designs give similar estimates of association in 93 investigations where both unrelated case-control and family-baseddesignshadbeenemployed.Estimatedoddsratiosdifferedbeyondchancebetweenthetwodesignsin onlyfourinstances(4%).Thesummaryrelativeoddsratio(ROR)(theratioofoddsratiosobtainedfromunrelatedcase- control and family-based studies) was close to unity (0.96 [95% confidence interval, 0.91–1.01]). There was no heterogeneity in the ROR across studies(amount of heterogeneity beyond chance I2?0%). Differences on whether results were nominally statistically significant (p , 0.05) or not with the two designs were common (opposite classification rates 14% and 17%); this reflected largely differences in power. Conclusions were largely similar in diverse subgroup analyses. Unrelated case-control and family-based designs give overall similar estimates of association.Wecannotruleoutrarelargebiasesorcommonsmallbiases. Citation:EvangelouE,TrikalinosTA,SalantiG,IoannidisJPA(2006)Family-basedversusunrelatedcase-controldesignsforgeneticassociations.PLoSGenet2(8):e123.DOI: 10.1371/journal.pgen.0020123 may be further confounded by genotyping error,