For these simulations, we used genotypes from the Wellcome Trust Case Control Consortium [48]. QC was performed as described in Gusev et al. [14]: we removed any SNPs that were below a MAF of 0.01, were above 0.002 missingness, or deviated from Hardy-Weinberg equilibrium at a P < 0.01. The resulting dataset had 14,526 individuals and 162,574 SNPs. We let heritability vary between 0.1 and 0.9, with the proportion of causal SNPs equal to 0.05 and 0.005 (i.e., 8,129 and 813 causal SNPs on average, respectively), and we simulated quantitative phenotypes from an additive model. For each simulation, effect sizes for causal SNPs were drawn from a normal distribution with mean zero and variance (i.e., average per-SNP heritability) determined by functional categories. To simulate realistic enrichment for the 53 categories in the baseline model plus the CNS cell-type group, we fit the model to the schizophrenia summary statistics [18] and took the resulting coefficients, replacing negative coefficients with 0. We then scaled these coefficients as needed to give the desired heritability at the desired level of polygenicity. For each simulation,
