Open AccessEuropean American Stratification in Ovarian Cancer Case Control Data: The Utility of Genome-Wide Data for Inferring Ancestry
Author(s) -
Paola Raska,
Edwin S. Iversen,
Ann Chen,
Zhihua Chen,
Brooke L. Fridley,
Jennifer Permuth-Wey,
Ya Yu Tsai,
Robert A. Vierkant,
Ellen L. Goode,
Harvey A. Risch,
Joellen M. Schildkraut,
Thomas A. Sellers,
Jill S. BarnholtzSloan
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0035235
Subject(s) - population stratification , biology , genome , genome wide association study , ancestry informative marker , genetics , population , 1000 genomes project , genetic variation , evolutionary biology , computational biology , allele frequency , gene , single nucleotide polymorphism , allele , genotype , demography , sociology
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.