Combining the case–control methodology with the small size transmission/disequilibrium test for multiallelic markers

Case–control studies compare marker-allele distributions in affected and unaffected individuals, and significant results may be due to linkage but can also simply reflect population structure. To test for linkage after obtaining a significant case–control finding, within-family analysis can be performed. In a transmission/disequilibrium test (TDT), genotypes of cases are compared to those of their parents to explore whether a specific allele, or marker, at a locus of interest is transmitted to a greater degree than Mendelian inheritance would warrant. For multiallelic markers, several authors have proposed extensions to the TDT. In this article, we propose a TDT test, utilizing the available information of a case–control study in the grouping of alleles for multiallelic markers, and thereby increase the statistical power of a TDT test with a small sample size.