We next repeated these simulations with a cell-type-specific mark—H3K4me3 in fetal brain cells—instead of a cell-type group as the simulated causal category. There are many more pairs of cell types that are highly correlated than there are highly correlated pairs of cell-type groups, and we are testing all cell types every time (Supplementary Figure S6). We found that when the level of enrichment was calibrated to give a realistic −log10(P) (based on results for the real data sets analyzed below; Online Methods), the simulated causal cell type was the most significant cell type in 78% of simulations, a cell-type with r2 > 0.5 to the causal cell type was most significant in 20% of simulations, and there was no significant cell type in 2% of simulations. In simulations with weak enrichment—again calibrating so that 50% of simulations have at least one significant cell type—we found that of the simulations with at least one significant cell type, only 4% had as the top cell type a cell type with r2 < 0.5 to the causal cell type.
