The power and statistical behaviour of allele-sharing statistics when applied to models with two disease loci

We have evaluated the power for detecting a common trait determined by two loci, using seven statistics, of which five are implemented in the computer program SimWalk2, and two are implemented in GENEHUNTER. Unlike most previous reports which involve evaluations of the power of allele-sharing statistics for a single disease locus, we have used a simulated data set of general pedigrees in which a two-locus disease is segregating and evaluated several nonparametric linkage statistics implemented in the two programs. We found that the power for detecting linkage using the S_all statistic in GENEHUNTER (GH, version 2.1), implemented as statistic E in SimWalk2 (version 2.82), is different in the two. The P values associated with statistic E output by SimWalk2 are consistently more conservative than those from GENEHUNTER except when the underlying model includes heterogeneity at a level of 50% where the P values output are very comparable. On the other hand, when the thresholds are determined empirically under the null hypothesis, S_all in GENEHUNTER and statistic E have similar power.