an OCD-spectrum disorder that has been previously hypothesized to be genetically related to GTS, additional studies in GTS and OCD samples have failed to replicate association with these variants (Table 2) [86, 88–93]. The largest study to date screened over 1,000 patients with GTS and found only two var321-positive individuals, one in a GTS patient and the other in a mother of a GTS patient who herself had OCD, but no tics. Both patients failed to transmit this mutation to their GTS affected offspring. While this study does not support a role for var321 in GTS, it should also be noted that due to the low frequency of SLITRK1 var321 in the general population (0.1%), even this sample size of 1000 cases is markedly underpowered to detect an association of such a rare allele [88]. Another large study evaluated 307 Costa Rican and 515 Ashkenazi patients for association between GTS and SLITRK1 [86]. No var321 alleles were identified in the Costa Rican sample, but five instances of var321 were found in Ashkenazi GTS patients, two of whom transmitted var321 to affected children. This high number of SLITRK1 var321 polymorphisms in the Ashkenazi sample prompted analysis of this variant in 256
