Although the genetic basis of Tourette Syndrome (TS) remains unclear, several candidate
genes have been implicated. Using a set of 382 TS individuals of European ancestry
we investigated four candidate genes for TS (HDC, SLITRK1, BTBD9, and SLC6A4) in an
effort to identify possibly causal variants using a targeted re-sequencing approach
by next generation sequencing technology. Identification of possible disease causing
variants under different modes of inheritance was performed using the algorithms implemented
in VAAST. We prioritized variants using Variant ranker and validated five rare variants
via Sanger sequencing in HDC and SLITRK1, all of which are predicted to be deleterious.
Intriguingly, one of the identified variants is in linkage disequilibrium with a variant
that is included among the top hits of a genome-wide association study for response
to citalopram treatment, an antidepressant drug with off-label use also in obsessive
compulsive disorder. Our findings provide additional evidence for the implication
of these two genes in TS susceptibility and the possible role of these proteins in
the pathobiology of TS should be revisited.
