title: Identity-by-descent graphs offer a flexible framework for imputation and both linkage and association analyses.
abstract: We demonstrate the flexibility of identity-by-descent (IBD) graphs for genotype imputation and testing relationships between genotype and phenotype. We analyzed chromosome 3 and the first replicate of simulated diastolic blood pressure. IBD graphs were obtained from complete pedigrees and full multipoint marker analysis, facilitating subsequent linkage and other analyses. For rare alleles, pedigree-based imputation using these IBD graphs had a higher call rate than did population-based imputation. Combining the two approaches improved call rates for common alleles. We found it advantageous to incorporate known, rather than estimated, pedigree relationships when testing for association. Replacing missing data with imputed alleles improved association signals as well. Analyses were performed with knowledge of the underlying model.
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Elizabeth Marchani
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, Seattle, WA 98195, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Glazner
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, Seattle, WA 98195, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Lewis
authors.affiliation: Department of Statistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Serge
authors.initials: S
authors.lastname: Sverdlov
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Thornton
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA ; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Wijsman