European American stratification in ovarian cancer case control data: the utility of genome-wide data for inferring ancestry.

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Raska, P; Iversen, E; Chen, A; Chen, Z; Fridley, BL; Permuth-Wey, J; Tsai, Y-Y; Vierkant, RA; Goode, EL; Risch, H; Schildkraut, JM; Sellers, TA; Barnholtz-Sloan, J

Published Date

  • 2012

Published In

Volume / Issue

  • 7 / 5

Start / End Page

  • e35235 -

PubMed ID

  • 22590501

Pubmed Central ID

  • PMC3348917

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0035235


  • eng

Conference Location

  • United States