Weighting affected sib pairs by marker informativity.

For the analysis of affected sib pairs (ASPs), a variety of test statistics is applied in genomewide scans with microsatellite markers. Even in multipoint analyses, these statistics might not fully exploit the power of a given sample, because they do not account for incomplete informativity of an ASP. For meta-analyses of linkage and association studies, it has been shown recently that weighting by informativity increases statistical power. With this idea in mind, the first aim of this article was to introduce a new class of tests for ASPs that are based on the mean test. To take into account how much informativity an ASP contributes, we weighted families inversely proportional to their marker informativity. The weighting scheme is obtained by use of the de Finetti representation of the distribution of identity-by-descent values. We derive the limiting distribution of the weighted mean test and demonstrate the validity of the proposed test. We show that it can be much more powerful than the classical mean test in the case of low marker informativity. In the second part of the article, we propose a Monte Carlo simulation approach for evaluating significance among ASPs. We demonstrate the validity of the simulation approach for both the classical and the weighted mean test. Finally, we illustrate the use of the weighted mean test by reanalyzing two published data sets. In both applications, the maximum LOD score of the weighted mean test is 0.6 higher than that of the classical mean test.