The widespread success in gene discovery leveraging de novo variation in ASD (De Rubeis et al., 2014; Dong et al., 2014; Iossifov et al., 2012, 2014; Neale et al., 2012; O’Roak et al., 2011, 2012; Sanders et al., 2012, 2015; Willsey et al., 2013) strongly argues for additional WES in TD. The current gene discovery by cohort size curves predict that increasing our study size to 2,517 trios would lead to the identification of ~21 hcTD genes, which is a similar order of magnitude to the 27 hcASD genes identified from 2,517 trios in Iossifov et al. (2014). Moreover, the integration of de novo CNV data should further increase the yield of risk genes (Sanders et al., 2015). The discovery of a large number of TD-associated genes will provide a critical substrate for model systems and systems-biological studies aimed at understanding the spatial, temporal, and cell-level dynamics of TD pathology (Parikshak et al., 2013; Willsey et al., 2013; Willsey and State, 2015; Xu et al., 2014) and, importantly, for the development of novel, more effective therapeutic targets.
