causal variants increases the size of the disease class, which is the proportion of haplotypes that carry one or more disease alleles [8]. The size of the disease class varied in the simulations both because the frequency of causal variants was allowed to vary, and because the disease class increases on average with the number of causal variants. To investigate the effect of the disease class on synthetic associations, we separated the results by size of disease class and found first that the larger the disease class the higher the chance of a significant synthetic association. We also find, however, that within a disease class size, the probability of significant synthetic associations decreases with the number of causal variants (Figure 3).
