Strategies for detecting susceptibility genes in a complex disease

One of the current issues in genetic epidemiology is detecting susceptibili ty genes on the genome. It is common now to undertake systematic screening of the genome using approaches based on a measure of the haplotype sharing in sib pairs. Here, we compare the efficiency of two statistics, the maximu m likelihood score (MLS) and the nonparametric linkage score (NPLa) on the simulated data provided for GAW11. A question often raised is whether it is better to perform a single-step or a two-step strategy. For the simulated model, and whatever the strategy used, we show here that the answer is not unequivocal. In both cases, the power to detect susceptibility genes in a s ingle replicate with MLS or NPL is extremely low. With two replicates, only one of the four simulated loci could be detected with reasonable power. Wh en gametic disequilibrium is suspected, methods testing for both linkage an d association might be more powerful. (C) 1999 Wiley-Liss, Inc.