Regional Admixture Mapping and Structured Association Testing Conceptual Unification and an Extensible General Linear Model 英文参考文献.docVIP

RegionalAdmixtureMappingandStructured AssociationTesting:ConceptualUnification andanExtensibleGeneralLinearModel David T.Redden1,2*,Jasmin Divers1,Laura Kelly Vaughan1,Hemant K.Tiwari1,T.Mark Beasley1,Jose′ R.Ferna′ndez1,2,3, Robert P.Kimberly4,Rui Feng1,Miguel A.Padilla1,Nianjun Liu1,Michael B.Miller5,David B.Allison1,2,3 1Department ofBiostatistics, SectiononStatisticalGenetics,UniversityofAlabama atBirmingham,Birmingham,Alabama,UnitedStatesofAmerica,2ClinicalNutrition Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States ofAmerica, 4Division of Clinical Immunology and Rheumatology, Department ofMedicine, University of Alabama at Birmingham,Birmingham,Alabama,UnitedStatesofAmerica,5DivisionofEpidemiology,UniversityofMinnesota,Minneapolis,Minnesota,UnitedStatesofAmerica Individual genetic admixture estimates, determined both across the genome and at specific genomic regions, have been proposed for use in identifying specific genomic regions harboring loci influencing phenotypes in regional admixturemapping(RAM).Estimatesofindividualancestrycanbeusedinstructuredassociationtests(SAT)toreduce confoundinginducedbyvariousformsofpopulationsubstructure.Althoughpresentedastwodistinctapproaches,we provide a conceptual framework in which both RAM and SAT are special cases of a more general linear model. We clarifywhichvariablesaresufficienttocondition uponinordertopreventspuriousassociationsandalsoprovidea simple closed form ‘‘semiparametric’’ method of evaluating the reliability of individual admixture estimates. An estimate of the reliability of individual admixture estimates is required to make an inherent errors-in-variables problem tractable. Casting RAM and SAT methods as a general linear model offers enormous flexibility enabling application to a rich set of phenotypes, populations, covariates, and sit