Comparison of linkage-disequilibrium methods for localization of genes influencing quantitative traits in humans.

Linkage disequilibrium has been used to help in the identification of genes predisposing to certain qualitative diseases. Although several linkage-disequilibrium tests have been developed for localization of genes influencing quantitative traits, these tests have not been thoroughly compared with one another. In this report we compare, under a variety of conditions, several different linkage-disequilibrium tests for identification of loci affecting quantitative traits. These tests use either single individuals or parent-child trios. When we compared tests with equal samples, we found that the truncated measured allele (TMA) test was the most powerful. The trait allele frequencies, the stringency of sample ascertainment, the number of marker alleles, and the linked genetic variance affected the power, but the presence of polygenes did not. When there were more than two trait alleles at a locus in the population, power to detect disequilibrium was greatly diminished. The presence of unlinked disequilibrium (D'*) increased the false-positive error rates of disequilibrium tests involving single individuals but did not affect the error rates of tests using family trios. The increase in error rates was affected by the stringency of selection, the trait allele frequency, and the linked genetic variance but not by polygenic factors. In an equilibrium population, the TMA test is most powerful, but, when adjusted for the presence of admixture, Allison test 3 becomes the most powerful whenever D'*>.15.