Properties of the multiallelic trend test

Disease genes can be mapped on the basis of associations between genetic markers and disease status, with the case-control design having the advantage of not requiring individuals from different generations. When the marker loci have multiple alleles, there has been debate on whether the power of tests for association increases or decreases. We show here that the multiple-allele version of Armitage's trend test has increased power over the two-allele version under the requirement of equifrequent alleles, but not in general. The trend test has the advantage of remaining valid even when the sampled population is not in Hardy-Weinberg equilibrium. A departure from Hardy-Weinberg means that association tests depend on gametic and nongametic linkage disequilibrium between marker and disease loci, and we illustrate the magnitude of these effects with simulated data.