title: European American stratification in ovarian cancer case control data: the utility of genome-wide data for inferring ancestry.
abstract: We investigated the ability of several principal components analysis (PCA)-based strategies to detect and control for population stratification using data from a multi-center study of epithelial ovarian cancer among women of European-American ethnicity. These include a correction based on an ancestry informative markers (AIMs) panel designed to capture European ancestral variation and corrections utilizing un-thinned genome-wide SNP data; case-control samples were drawn from four geographically distinct North-American sites. The AIMs-only and genome-wide first principal components (PC1) both corresponded to the previously described North or Northwest-Southeast axis of European variation. We found that the genome-wide PCA captured this primary dimension of variation more precisely and identified additional axes of genome-wide variation of relevance to epithelial ovarian cancer. Associations evident between the genome-wide PCs and study site corroborate North American immigration history and suggest that undiscovered dimensions of variation lie within Northern Europe. The structure captured by the genome-wide PCA was also found within control individuals and did not reflect the case-control variation present in the data. The genome-wide PCA highlighted three regions of local LD, corresponding to the lactase (LCT) gene on chromosome 2, the human leukocyte antigen system (HLA) on chromosome 6 and to a common inversion polymorphism on chromosome 8. These features did not compromise the efficacy of PCs from this analysis for ancestry control. This study concludes that although AIMs panels are a cost-effective way of capturing population structure, genome-wide data should preferably be used when available.
authors.affiliation: Department of Epidemiology and Biostatistics, Case School of Medicine, Cleveland, Ohio, United States of America. pxo11@case.edu
authors.forename: Paola
authors.initials: P
authors.lastname: Raska
authors.forename: Edwin
authors.initials: E
authors.lastname: Iversen
authors.forename: Ann
authors.initials: A
authors.lastname: Chen
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Chen
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Jennifer
authors.initials: J
authors.lastname: Permuth-Wey
authors.forename: Ya-Yu
authors.initials: YY
authors.lastname: Tsai
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.forename: Harvey
authors.initials: H
authors.lastname: Risch
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
mesh_terms: D016022:Case-Control Studies; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D009656:North America; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*