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OBTAINING ROBUST TDT-TYPE CANDIDATE-GENE ASSOCIATION TESTS FOR A FAMILY OF GENETIC MODELS

Introduction The transmission disequilibrium test (TDT) of Spielman et al. (1993) was developed as test of linkage between a marker locus and a disease in the presence of allelic association and can also be used in testing for association between a candidate gene and a disease. By focusing on a specific genetic model in the candidate gene setting more powerful tests can be obtained. Schaid and Sommer (1994) derived TDT-type statistics that are, respectively, most powerful for dominant and recessive models and showed that the TDT is optimal under an additive or multiplicative model. Since the underlying genetic model is usually not known in advance, applying the results from efficiency robustness (Gastwirth, 1966, 1985 and Shih and Whittemore, 2000), Zheng et al. (2002) studied two robust tests: maximin efficient robust test (MERT) and MAX test when the underlying genetic model is one of the dominant, additive, multiplicative, and recessive models. The MERT and MAX of Zheng et al. (2002) are, respectively, linear combination and maximum of two optimal score tests, corresponding to the recessive and dominant models. Here we consider a larger family of genetic models defined in terms of genotype relative risks, including the four basic models, and show that the MERT and MAX of Zheng et al. (2002) can still be used for this larger family of genetic models.