LOD score exclusion analyses for candidate disease susceptibility genes using case-parents design*

Abstract

Abstract The focus of almost all the association studies of candidate genes is to test for their importance. We recently developed a LOD score approach that can be used to test against the importance of candidate genes for complex diseases and quantitative traits in random samples. As a complementary method to regular association analyses, our LOD score approach is powerful but still affected by the population admixture, though it is more coservative. To control the confounding effect of population heterogeneity, we develop here a LOD score exclusion analysis using case-parents design, the basic design of the transmission disequilibrium test (TDT) approach that is immune to populaion admixture. In the analysis, specific genetic effects and inheritance models at cfandidate genes can be analyzed and if a LOD score is ≤−2.0, the locus can be excluded from having an effect larger than that specified. Simulations show that this approach has reasonable power to exclude a candidate gene having small genetic effe...