title: Estimating and adjusting for ancestry admixture in statistical methods for relatedness inference, heritability estimation, and association testing.
abstract: It is well known that genetic association studies are not robust to population stratification. Two widely used approaches for the detection and correction of population structure are principal component analysis and model-based estimation of ancestry. These methods have been shown to give reliable inference on population structure in unrelated samples. We evaluated these two approaches in Mexican American pedigrees provided by the Genetic Analysis Workshop 18. We also estimated identity-by-descent sharing probabilities and kinship coefficients, with adjustment for ancestry admixture, to confirm documented pedigree relationships as well as to identify cryptic relatedness in the sample. We also estimated the heritability of the first simulated replicate of diastolic blood pressure (DBP). Finally, we performed an association analysis with simulated DBP, comparing the performance of an association method that corrects for population structure but does not account for relatedness to a method that adjusts for both population and pedigree structure. Analyses with simulated DBP were performed with knowledge of the underlying trait model.
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Thornton
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Conomos
authors.affiliation: Department of Statistics, University of Washington, 313 Padelford Hall, Seattle, WA 98195, USA.
authors.forename: Serge
authors.initials: S
authors.lastname: Sverdlov
authors.affiliation: Department of Medicine, Division of Medical Genetics, University of Washington, Health Sciences Building, K-253, Box 357720, Seattle, WA 98195, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Blue
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Charles Yk
authors.initials: CY
authors.lastname: Cheung
authors.affiliation: Department of Statistics, University of Washington, 313 Padelford Hall, Seattle, WA 98195, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Glazner
authors.affiliation: Department of Statistics, University of Washington, 313 Padelford Hall, Seattle, WA 98195, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Lewis
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA ; Department of Medicine, Division of Medical Genetics, University of Washington, Health Sciences Building, K-253, Box 357720, Seattle, WA 98195, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Wijsman