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An Arabidopsis Example of Association Mapping in Structured Samples 英文参考文献
AnArabidopsisExampleofAssociationMapping
inStructuredSamples
Keyan Zhao1,Mar?′aJose′ Aranzana1,Sung Kim1,Clare Lister2,Chikako Shindo2,Chunlao Tang1,
Christopher Toomajian1,Honggang Zheng1,Caroline Dean2,Paul Marjoram3,Magnus Nordborg1*
1 Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States of America, 2 Department of Cell and Developmental
Biology, John Innes Centre, Norwich, United Kingdom, 3 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles,
California,UnitedStatesofAmerica
A potentially serious disadvantage of association mapping is the fact that marker-trait associations may arise from
confounding population structure as well as from linkage to causative polymorphisms. Using genome-wide marker
data,wehavepreviouslydemonstratedthattheproblemcanbesevereinaglobalsampleof95Arabidopsisthaliana
accessions,andthatestablishedmethodsforcontrollingforpopulationstructurearegenerallyinsufficient.Here,we
usethesamesampletogetherwithanumberofflowering-relatedphenotypesanddata-perturbationsimulationsto
evaluateawiderrangeofmethodsforcontrollingforpopulationstructure.Wefindthat,intermsofreducingthefalse-
positive rate while maintaining statistical power, a recently introduced mixed-model approach that takes genome-
wide differences in relatedness into account via estimated pairwise kinship coefficients generally performs best. By
combiningtheassociationresultswithresultsfromlinkagemappinginF2crosses,weidentifyonepreviouslyknown
truepositiveandseveralpromisingnewassociations,butalsodemonstratetheexistenceofbothfalsepositivesand
false negatives. Our results illustrate the potential of genome-wide association scans as a tool for dissecting the
geneticsofnaturalvariation,whileatthesametimehighlightingthepitfalls.Theimportanceofstudydesignisclear;
our study is severely under-powered both in terms of sample size and marker density. Our results also provide a
striki
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