Using principal components of genetic variation for robust and powerful detection of gene-gene interactions in case-control and case-only studies.

ABSTRACT: Many popular methods for exploring gene-gene interactions, including the case-only approach, rely on the key assumption that physically distant loci are in linkage equilibrium in the underlying population. These methods utilize the presence of correlation between unlinked loci in a disease-enriched sample as evidence of interactions among the loci in the etiology of the disease. We use data from the CGEMS case-control genome-wide association study of breast cancer to demonstrate empirically that the case-only and related methods have the potential to create large-scale false positives because of the presence of population stratification (PS) that creates long-range linkage disequilibrium in the genome. We show that the bias can be removed by considering parametric and nonparametric methods

SUBMITTER: Bhattacharjee S 

PROVIDER: S-EPMC2833365 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature