Bayesian Linkage Analysis of Categorical Traits for Arbitrary Pedigree Designs 英文参考文献.docVIP

Bayesian Linkage Analysis of Categorical Traits for Arbitrary Pedigree Designs 英文参考文献.doc

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Bayesian Linkage Analysis of Categorical Traits for Arbitrary Pedigree Designs 英文参考文献

BayesianLinkageAnalysisofCategoricalTraitsfor ArbitraryPedigreeDesigns AbraBrisbin1*,MyrnaM.Weissman2,AbbyJ.Fyer2,StevenP.Hamilton3,JamesA.Knowles4 ,Carlos D.Bustamante1,5,JasonG.Mezey1,6 1DepartmentofBiologicalStatisticsandComputationalBiology,CornellUniversity,Ithaca,NewYork,UnitedStatesofAmerica,2DepartmentofPsychiatry,Collegeof PhysiciansandSurgeons,ColumbiaUniversityandNewYorkStatePsychiatricInstitute,NewYork,NewYork,UnitedStatesofAmerica,3DepartmentofPsychiatryand InstituteforHumanGenetics,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica,4ZilkhaNeurogeneticInstitute,KeckSchoolof Medicine,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica,5DepartmentofGenetics,StanfordUniversitySchoolofMedicine,Stanford, California,UnitedStatesofAmerica,6DepartmentofGeneticMedicine,WeillCornellMedicalCollege,NewYork,NewYork,UnitedStatesofAmerica Abstract Background: Pedigreestudiesofcomplexheritable diseasesoftenfeaturenominalorordinalphenotypicmeasurements andmissinggeneticmarkerorphenotypedata. Methodology:WehavedevelopedaBayesianmethodforLinkageanalysisofOrdinalandCategoricaltraits(LOCate)that cananalyzecomplexgenealogicalstructureforfamilygroupsandincorporatemissingdata.LOCateusesaGibbssampling approachtoassesslinkage,incorporatingasimulatedtemperingalgorithmforfastmixing.WhileourtreatmentisBayesian, we develop a LOD (log of odds) score estimator for assessing linkage from Gibbs sampling that is highly accurate for simulateddata.LOCateisapplicabletolinkageanalysisforordinalornominaltraits,aversatilitywhichwedemonstrateby analyzingsimulateddatawithanominaltrait,onwhichLOCateoutperformsLOT,anexistingmethodwhichisdesignedfor ordinal traits. We additionally demonstrate our method’s versatility by analyzing a candidate locus (D2S1788) for panic disorderinhumans,inadatasetwithalargeamountofmissingdata,whichLOTwasunabletohandle. Conclusion: LOCate’s accuracy and applicability to both ordinal and nominal traits will prove u

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