Power comparison of parametric and nonparametric linkage tests in small pedigrees

When the mode of inheritance of a disease is unknown, the LOD-score method of linkage analysis must take into account uncertainties in model parameter s. We have previously proposed a parametric linkage test called "MFLOD," wh ich does not require specification of disease model parameters. In the pres ent study, we introduce two new model-free parametric linkage tests, known as "MLOD" and "MALOD." These tests are defined, respectively, as the LOD sc ore and the admixture LOD score, maximized (subject to the same constraints as MFLOD) over disease-model parameters. We compared the power of these th ree parametric linkage tests and that of two nonparametric linkage tests, N PLall, and NPLpairs, which are implemented in GENEHUNTER. With the use of s mall pedigrees and a fully informative marker, we found the powers of MLOD, NPLall, and NPLpairs, to be almost equivalent to each other and not far be low that of a LOD-score analysis performed under the assumption the correct genetic parameters. Thus, linkage analysis is not much hindered by uncerta in mode of inheritance. The results also suggest that both parametric and n onparametric methods are suitable for linkage analysis of complex disorders in small pedigrees. However, whether these results apply to large pedigree s remains to be answered.