Power and robustness of a score test for linkage analysis of quantitative traits using identity by descent data on sib pairs

Identification of genes involved in complex traits by traditional (lod scor e) linkage analysis is difficult due to many complicating factors. An unfor tunate draw back of non-parametric procedures in general, though, is their low power to detect genetic effects. Recently, Dudoit and Speed [2000] prop osed using a (likelihood-based) score test for detecting linkage with IBD d ata on sib pairs. This method uses the likelihood for theta, the recombinat ion fraction between a trait locus and a marker locust conditional on the p henotypes of the two sibs to test the null hypothesis of no linkage (theta = 1/2). Although a genetic model must be specified, the approach offers sev eral advantages. This paper presents results of simulation studies characte rizing the power and robustness properties of this score test for linkage, and compares the power of the test to the Haseman-Elston and modified Hasem an-Elston tests. The score test is seen to have impressively high power acr oss a broad range of true and assumed models, particularly under multiple a scertainment. Assuming an additive model with a moderate allele frequency, in the range of p = 0.2 to 0.5, along with heritability H = 0.3 and a moder ate residual correlation p = 0.2 resulted in a very good overall performanc e across a wide range of trait-generating models. Generally, our results in dicate that this score test for linkage offers a high degree of protection against wrong assumptions due to its strong robustness when used with the r ecommended additive model.