Since clinical end-point traits are often defined by quantitative precursors, it may be a more prudent strategy to analyze the quantitative phenotypes without dichotomizing them into binary traits.
Although some methods have been developed for testing transmission disequilibrium in the context of quantitative traits, these are not direct extensions of the classical TDT.
We propose a simple logistic regression based test that can be analytically shown to be statistically equivalent to the TDT for binary traits, and hence is not susceptible to the presence of population stratification in the data.
The proposed method can be easily extended to incorporate multivariate
phenotypes. We perform Monte-Carlo simulations under a wide spectrum of genetic models and probability distributions of the
quantitative trait values to evaluate the power of the proposed procedure and compare with the FBAT approach with identical data.
We find that our method yields more power than FBAT if we suitably incorporate trios with both parents heterozygous in our likelihood as well as for multivariate phenotypes based on principal components.
We apply our method to analyze externalizing symptoms, an alcoholism related endophenotype from the Collaborative Study on the Genetics Of Alcoholism (COGA) project.
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