Simulating inheritance of a genetically heterogeneous disease can be performed in different ways. To ensure that all variants have a low effect, we have chosen to simulate all variants within a group with the same PAR. An alternative scenario is to simulate all variants, in a group, with the same relative risk (RR), and let the PAR vary according to the mutation-frequency. Under this scenario, a single, or few, common mutations may carry a large part of the total risk, and this scenario is hence equivalent to a scenario with a single, or few, disease-contributing variants. A few common variants carrying a relatively large risk is exactly the what studies using panels of SNPs are designed for, and our focus has therefore been on scenarios where the disease risk can not be explained by a few variants. Note further that all investigated methods are able to identify cases where a few mutations carry a large part of the total risk (see Figure 3). We have further included the comparison of the Encode populations, to cover a scenario where the mutation-frequencies are distributed according to an actual population.
