Choice of scores in trend tests for case-control studies of candidate-gene associations

When applying the Cochran-Armitage (CA) trend test for an association between a candidate allele and a disease in a case-control study, a set of scores must be assigned to the genotypes. SASIENI (1997, Biometrics 53, 1253-1261) suggested scores for the recessive, additive, and dominant models but did not examine their statistical properties. Using the criteria of minimizing the required sample size of the CA trend test to achieve prespecified type I and type II errors, we show that the scores given by SASIENI (1997) are optimal for the recessive and dominant models and locally optimal for the additive one. Moreover, the additive scores are shown to be locally optimal for the multiplicative model. The tests are applied to a real dataset.