harboring multiple de novo variants and recorded when the number of genes with two variants and the number of genes with three or more variants in the simulated data matched the number observed in our study (4 and 1, respectively). Based on the frequency of these occurrences versus gene number, we determined the MLE of the number of TD risk genes to be 420 genes (Figure 5A). Alternatively, based on methods we have used previously to evaluate target size in ASD (Sanders et al., 2011, 2012), we estimate 447 genes (95% CI 136.7–932.7).
