Model-free vs. model-based linkage analysis: a false dichotomy?

Abstract

The aim of this article is to dispel some misunderstandings concerning the concepts of model-free or nonparametric linkage analysis (usually meaning affecteds-only analysis) and model-based or parametric analysis (usually meaning classical lod scores) and the implications of these concepts for the linkage analysis of complex genetic diseases. I review basic principles and then briefly indicate actual research findings. Readers may be surprised to learn that, technically, lod score analysis is also nonparametric. All this taken together indicates that classical lod score analysis, performed under a couple of different sets of genetic assumptions and corrected for multiple tests, is often actually superior to model-free analyses, even when the true genetic model is complex and unknown.