High-throughput SNP arrays provide estimates of genotypes for up to one million loci, often used in genome-wide association studies. While these estimates are typically very accurate, genotyping errors do occur, which can influence in particular the most extreme test statistics and p-values. Estimates for the genotype uncertainties are also available, although typically ignored. In this manuscript, we develop a framework to incorporate these genotype uncertainties in case-control studies for any genetic model. We verify that using the assumption of a “local alternative” in the score test is very reasonable for effect sizes typically seen in SNP association studies, and show that the power of the score test is simply a function of the correlation of the genotype probabilities with the true genotypes. We demonstrate that the power to detect a true association can be substantially increased for difficult to call genotypes, resulting in improved inference in association studies.
Ruczinski, Ingo; Li, Qing; Carvalho, Benilton; Fallin, M. Daniele; Irizarry, Rafael A.; and Louis, Thomas A., "ASSOCIATON TESTS THAT ACCOMMODATE GENOTYPING ERRORS" (January 2009). Johns Hopkins University, Dept. of Biostatistics Working Papers. Working Paper 181.