theory47,48, haploinsufficiency appears more common and penetrant than triplosensitivity for severe developmental phenotypes. While this cohort does not represent a random sampling of individuals with ID/DD and includes some individuals without ID or DD, our estimates are likely applicable to ID/DD in general. For example, the average CNV burden across 15 genome-wide studies of ID/DD (combined sample size of 1,021) was estimated to be ~13.7%, similar to our estimate of 14.2%, in a literature survey by Miller et al.49 (note that this estimate was derived by averaging the diagnostic yields for all studies with a genome-wide resolution of 1 Mbp or better as indicated in Table 2 of Miller et al.). Furthermore, the observed enrichment for many loci known to contribute to ID/DD risk (Table 1) and individual genes previously identified to be disrupted among affected individuals (Supplementary Table 12) clearly supports the applicability of the inferences generated here for both ID/DD specifically and neurological disease (e.g. schizophrenia, autism, etc.) in general.
