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Polytomous phenotypes arise when a disease has multiple subtypes or when two dichotomous phenotypes are analyzed simultaneously. Few software programs offer the option to analyze such phenotypes in family studies, and none implements conditional polytomous logistic regression for within-family analysis robust to population stratification. We introduce  Polyunphased , an extension to polytomous phenotypes of the  Unphased  package, a flexible software tool for genetic association analysis in nuclear families. Like  Unphased ,  Polyunphased  is written in C++ and runs from the command line or from a Java graphical user interface. Most  Unphased  options remain available in  Polyunphased , including those handling missing parental genotypes while preserving robustness to population stratification, and the modelling options. Simulation studies confirmed the expected statistical behaviour of the maximum likelihood estimates of the association parameters of the conditional logistic regression model when the corresponding association parameters in the parental term of the likelihood function are set to 0, but revealed convergence problems when estimating these parental association parameters separately. The former approach is thus recommended with polytomous phenotypes.

Polyunphased: an extension to polytomous outcomes of the Unphased package for family-based genetic association analysis