A robust linkage analysis method using combined allele sharing and transmission disequilibrium information from case-parent tetrad families.

ABSTRACT

There are two types of linkage information, the allele sharing information and transmission disequilibrium information, that can be extracted from case-parent tetrad families for deriving statistics for test of linkage. By extracting allele sharing information the mean test can be derived. By extracting transmission disequilibrium information the transmission/disequilibrium test (TDT) can be derived. The power performances of the two tests are different with respect to the extent of linkage disequilibrium. The TDT is more powerful than the mean test when the extent of linkage disequilibrium is moderate to strong, but the mean test has better power performance than the TDT when linkage disequilibrium is weak. Some previous studies have proposed several post-combination analysis methods, which combine the two tests after they are derived using the two types of linkage information respectively, to yield robust test statistics against the interference of linkage disequilibrium. Instead of adopting the post-combination approach, in this paper we investigate the approach of using the pre-combination idea to yield robust statistics for test of linkage. The pre-combination methods combine the two types of linkage information first, and then use the combined information to construct robust test statistics. Simulation studies are conducted to compare the power performances of the proposed pre-combination tests with those of the existing post-combination methods.