AUTHOR=Alexander John , Potamianou Hera , Xing Jinchuan , Deng Li , Karagiannidis Iordanis , Tsetsos Fotis , Drineas Petros , Tarnok Zsanett , Rizzo Renata , Wolanczyk Tomasz , Farkas Luca , Nagy Peter , Szymanska Urszula , Androutsos Christos , Tsironi Vaia , Koumoula Anastasia , Barta Csaba ,  TSGeneSEE , Sandor Paul , Barr Cathy L. , Tischfield Jay , Paschou Peristera , Heiman Gary A. , Georgitsi Marianthi 

TITLE=Targeted Re-Sequencing Approach of Candidate Genes Implicates Rare Potentially Functional Variants in Tourette Syndrome Etiology

JOURNAL=Frontiers in Neuroscience

VOLUME=10

YEAR=2016

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2016.00428

DOI=10.3389/fnins.2016.00428

ISSN=1662-453X

ABSTRACT=<p>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 (<italic>HDC, SLITRK1, BTBD9</italic>, and <italic>SLC6A4</italic>) 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 <italic>HDC</italic> and <italic>SLITRK1</italic>, 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.</p>