A CONDITIONAL INFERENCE FRAMEWORK FOR EXTENDING THE TRANSMISSION DISEQUILIBRIUM TEST/

The transmission/disequilibrium test (TDT) of Terwilliger and Ott [Hum Hered 1992;42:337-346] and Spielman et al. [Am J Hum Genet 1993;52:50 6-516] is widely used to detect linkage and/or association between a g enetically influenced disease and the alleles of a codominant marker l ocus. The TDT was specifically designed to avoid the spurious populati on associations produced by ethnic stratification of a sample of affec ted people. In this paper, we describe permutation extensions of the T DT that share this advantage. Our conditional inference framework perm its extensions to multiple alleles, multiple loci, unaffected siblings , and genotypic rather than allelic associations. In the case of multi ple loci, the conditional perspective provides a straightforward corre ction for multiple tests that can be substantially more powerful than the standard Bonferroni correction.