An Improved Score Test for Genetic Association Studies

Large-scale genome-wide association studies (GWAS) have become feasible recently because of the development of bead and chip technology. However, the success of GWAS partially depends on the statistical methods that are able to manage and analyze this sort of large-scale data. Currently, the commonly used tests for GWAS include the Cochran-Armitage trend test, the allelic chi(2) test, the genotypic chi(2) test, the haplotypic chi(2) test, and the multi-marker genotypic chi(2) test among others. From a methodological point of view, it is a great challenge to improve the power of commonly used tests, since these tests are commonly used precisely because they are already among the most powerful tests. In this article, we propose an improved score test that is uniformly more powerful than the score test based on the generalized linear model. Since the score test based on the generalized linear model includes the aforementioned commonly used tests as its special cases, our proposed improved score test is thus uniformly more powerful than these commonly used tests. We evaluate the performance of the improved score test by simulation studies and application to a real data set. Our results show that the power increases of the improved score test over the score test cannot be neglected in most cases. Genet. Epidemiol. 35: 350-359, 2011. (C) 2011 Wiley-Liss, Inc.