Including non-informative parents in transmission-based association tests.

The classical transmission disequilibrium test (TDT) based on a trio design uses information only on the allele transmitted by a heterozygous parent at a marker locus as homozygous parents are non-informative about linkage. However, the phenotype of an offspring depends on the alleles transmitted by both parents, irrespective of whether the parents are homozygous or heterozygous, and hence carry useful information on association. In this article, we propose modifications to the TDT procedures by incorporating transmission data on both parents in an informative trio to explore possible gain in power in detecting association. For a binary trait, we use a goodness-of-fit χ2 test, whereas for a quantitative trait, we devise two tests: one based on a bivariate response logistic model and the other using a quasi-likelihood approach. We evaluate the type 1 errors and the powers of the proposed tests with those of the classical TDT procedures for both binary and quantitative traits based on extensive simulations. We find that the inclusion of transmission data on non-informative parents yields marginally higher power in the logistic regression approach but results in substantial gain in power in the quasi-likelihood approach. We apply our proposed methods to analyze a count phenotype related to alcoholism.