The design parameters for a two-stage study include the total cost, total sample size, size of the first and second sub-samples and rejection criterion at the end of the first stage. Studies with only two stages are considered, although more could be performed. Some of these parameters are constrained in advance, with the others then chosen to optimise some objective. One approach is to consider the genotyping cost as fixed and then find parameters that give the most power [21,22]. A general rule of thumb, considering a number of disease models and correlation structures between markers, is to allocate 75 per cent of resources to the first stage and then carry the most promising 10 per cent of markers to the second [22]. Here, the sample size is a function of the genotype unit cost and the number of markers, within the overall cost constraint.
