Estimating and adjusting for ancestry admixture in statistical methods for relatedness inference, heritability estimation, and association testing.

ABSTRACT

It is well known that genetic association studies are not robust to population stratification. Two widely used approaches for the detection and correction of population structure are principal component analysis and model-based estimation of ancestry. These methods have been shown to give reliable inference on population structure in unrelated samples. We evaluated these two approaches in Mexican American pedigrees provided by the Genetic Analysis Workshop 18. We also estimated identity-by-descent sharing probabilities and kinship coefficients, with adjustment for ancestry admixture, to confirm documented pedigree relationships as well as to identify cryptic relatedness in the sample. We also estimated the heritability of the first simulated replicate of diastolic blood pressure (DBP). Finally, we performed an association analysis with simulated DBP, comparing the performance of an association method that corrects for population structure but does not account for relatedness to a method that adjusts for both population and pedigree structure. Analyses with simulated DBP were performed with knowledge of the underlying trait model.