Robust tests for matched case-control genetic association studies

Although GMS and GME are powerful statistically, they could be seriously affected by known confounding factors such as gender, age and race. Therefore, in this paper, via comparing the difference of Hardy-Weinberg disequilibrium coefficients between the cases and the controls within each sub-population, we propose the stratified genetic model selection (SGMS) and exclusion (SGME) methods which could eliminate the effect of confounding factors by adopting a matching framework. Our goal in this paper is to investigate the robustness of the proposed statistics and compare them with other commonly used efficiency robust tests such as MAX3 and χ2 with 2 degrees of freedom (df) test in matched case-control association designs through simulation studies.Simulation results showed that if the mean genetic effect of the heterozygous genotype is between those of the two homozygous genotypes, then the proposed tests and MAX3 are preferred. Otherwise, χ2 with 2 df test may be used. To illustrate the robust procedures, the proposed tests are applied to a real matched pair case-control etiologic study of sarcoidosis.The population-based case-control association study is a powerful approach in detecting the association between a candidate marker and a disease. Compared with the family-based association study which recruits samples from family members, the case-control study is more cost effective because cases and controls are unrelated hence easy to recruit from population. To test the genetic association using the case-control design, the genotypic data for a bi-allelic marker are usually described by a 2 × 3 table where rows represent the disease status and columns represent the genotypic counts. Hence, to test for genetic association is equivalent to test for association between the rows and the columns. Generally, the Pearson's χ2 with 2 df test can be used to detect such an association. Besides, if a linear trend among the rows can be assumed, a more powerful test which utili