Studies of de novo sequence variation using whole-exome sequencing (WES) have proven to be a powerful approach to systematic gene discovery in genetically complex neurodevelopmental disorders (NDDs) apart from TD (Bilgüvar et al., 2010; de Ligt et al., 2012; Deciphering Developmental Disorders Study, 2015, 2017; Epi4K Consortium, 2016; Allen et al., 2013; EuroEPINOMICS-RES Consortium et al., 2014; Rauch et al., 2012), particularly autism spectrum disorders (ASDs) (De Rubeis et al., 2014; Dong et al., 2014; Iossifov et al., 2014; Iossifov et al., 2012; Neale et al., 2012; O’Roak et al., 2011, 2012; Sanders et al., 2012, 2015; Willsey et al., 2013). In light of these findings and our previous results suggesting a role for de novo CNVs, we performed WES in 325 (311 after quality control) TD parent-child trios from the Tourette International Collaborative Genetics group (TIC Genetics; http://tic-genetics.org) to identify de novo single-nucleotide variants (SNVs) and insertion-deletion variants (indels). We observe significant evidence for the contribution of de novo likely gene-disrupting (LGD) variants (insertion of premature stop codon, frameshift, or canonical splice-site variant) to TD. We then replicate these
