A Disequilibrium Coefficient Approach to Hardy-Weinberg Testing

A comparison was made of various tests for Hardy-Weinberg equilibrium, with emphasis on methods for multiple alleles. For an overall test of deviations from equilibrium, the classical chi-square goodness-of-fit test generally performs well, with continuity corrections needed for extreme gene frequencies or extreme departures from equilibrium. For small samples, probability tests are preferable and for multiple alleles these probability tests may be performed on a sample of all possible sets of genotypic frequencies having a fixed set of sample gene frequencies. Numerical work showed that the continuity-corrected chi-square was the most conservative test procedure, and the uncorrected chi-square the least conservative. With multiple alleles, a better appreciation of the nature of departures from equilibrium is given by the use of disequilibrium coefficients, defined for each heterozygote as the difference between observed and expected frequencies. Likelihood-ratio tests can be used to test each of these coefficients individually but a satisfactory procedure is to divide the squared estimate of each coefficient by its estimated variance and regard the ratio as a single-degree-of-freedom chi-square. Numerical studies confirmed the validity of this approach, which has the great advantage of not requiring solutions of nonlinear equations.