A rapid association test procedure robust under different genetic models accounting for population stratification

Abstract

Objective: For genome-wide association studies (GWAS) using case-control data with stratification, a commonly used association test is the generalized Armitage (GA) trend test implemented in the software EIGENSTRAT. The GA trend test uses principal component analysis to correct for population stratification. It usually assumes an additive disease model and can have high power when the underlying disease model is additive or multiplicative, but may have relatively low power when the underlying disease model is recessive or dominant. The purpose of this paper is to provide a test procedure for GWAS with increased power over the GA trend test under the recessive and dominant models, while maintaining the power of the GA trend test under the additive and multiplicative models. Methods: We extend a Hardy-Weinberg disequilibrium (HWD) trend test for a homogeneous population to account for population stratification, and then propose a robust association test procedure for GWAS that incorporates information from the extended HWD trend test into the GA trend test. Results and Conclusions: Our simulation studies and application of our method to a GWAS data set indicate that our proposed method can achieve the purpose described above.