title: Ancestry estimation and control of population stratification for sequence-based association studies.
abstract: Estimating individual ancestry is important in genetic association studies where population structure leads to false positive signals, although assigning ancestry remains challenging with targeted sequence data. We propose a new method for the accurate estimation of individual genetic ancestry, based on direct analysis of off-target sequence reads, and implement our method in the publicly available LASER software. We validate the method using simulated and empirical data and show that the method can accurately infer worldwide continental ancestry when used with sequencing data sets with whole-genome shotgun coverage as low as 0.001×. For estimates of fine-scale ancestry within Europe, the method performs well with coverage of 0.1×. On an even finer scale, the method improves discrimination between exome-sequenced study participants originating from different provinces within Finland. Finally, we show that our method can be used to improve case-control matching in genetic association studies and to reduce the risk of spurious findings due to population structure.
authors.affiliation: 1] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. [3].
authors.forename: Chaolong
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1] Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. [2].
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bragg-Gresham
authors.affiliation: Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Kang
authors.affiliation: Department of Ophthalmology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania, USA.
authors.forename: Dwight
authors.initials: D
authors.lastname: Stambolian
authors.affiliation: Division of Epidemiology and Clinical Research, National Eye Institute, Bethesda, Maryland, USA.
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.affiliation: Department of Ophthalmology, University of Michigan Kellogg Eye Center, Ann Arbor, Michigan, USA.
authors.forename: Kari E
authors.initials: KE
authors.lastname: Branham
authors.affiliation: Department of Ophthalmology, University of Michigan Kellogg Eye Center, Ann Arbor, Michigan, USA.
authors.forename: John
authors.initials: J
authors.lastname: Heckenlively
authors.affiliation: Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Fulton
authors.affiliation: Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.affiliation: Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Mardis
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Xihong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, Bethesda, Maryland, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.affiliation: 1] Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. [2] Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zöllner
authors.affiliation: Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
mesh_terms: D001483:Base Sequence; D003198:Computer Simulation; D056726:Genetic Association Studies / Q000379:methods*; D005828:Genetics, Population / Q000379:methods*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D025341:Principal Component Analysis; D017422:Sequence Analysis, DNA; D012984:Software