THE RELATIVE EFFICIENCY OF THE HARDY-WEINBERG EQUILIBRIUM-LIKELIHOOD AND THE CONDITIONAL ON PARENTAL GENOTYPE-LIKELIHOOD METHODS FOR CANDIDATE GENE ASSOCIATION STUDIES

Selecting a control group that is perfectly matched for ethnic ancestr y with a group of affected individuals is a major problem in studying the association of a candidate gene with a disease. This problem can b e avoided by a design that uses parental data in place of nonrelated c ontrols. Schaid and Sommer presented two new methods for the statistic al analysis using this approach: (1) a likelihood method (Hardy-Weinbe rg equilibrium [HWE] method), which rests on the assumption that HWE h olds, and (2) a conditional likelihood method (conditional on parental genotype [CPG] method) appropriate when HWE is absent. Schaid and Som mer claimed that the CPG method can be more efficient than the HWE met hod, even when equilibrium holds. It can be shown, however, that in th e equilibrium situation the HWE method is always more efficient than t he CPG method. For a dominant disease, the differences are slim. But f or a recessive disease, the CPG method requires a much larger sample s ize to achieve a prescribed power than the HWE method. Additionally, w e show how the relative risks for the various candidate-gene genotypes can be estimated without relying on iterative methods. For the CPG me thod, we present an asymptotic power approximation that is sufficientl y precise for planning the sample size of an association study.