Targeted re-sequencing approach of candidate genes implicates rare potentially functional variants in Tourette Syndrome etiology
Open accessAbstract
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 tolerance 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.
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There is an ancestral S330A mutation of SLITRK1 that may be involved in obsessive-compulsive disorders like Tourette's Syndrome.
“Among those mutations we found through an exhaustive literature review, there is an ancestral S330A mutation of SLITRK1 that may be involved in obsessive-compulsive disorders like Tourette’s Syndrome [116, 117].”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [117]
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Self-domestication in Homo sapiens: Insights from comparative genomics
Theofanopoulou, C., Gastaldon, S., O’Rourke, T., Samuels, B. D., Messner, A., Martins, P. T., Delogu, F., Alamri, S., & Boeckx, C. (2017) · PLOS ONE · doi:10.1371/journal.pone.0185306 · Cited by 174 · see citing works
- Authors
- Alexander, J., Potamianou, H., Xing, J., Deng, L., Karagiannidis, I., Tsetsos, F., Drineas, P., Tarnok, Z., Rizzo, R., Wolanczyk, T., Farkas, L., Nagy, P., Szymanska, U., Androutsos, C., Tsironi, V., Koumoula, A., Barta, C., Sandor, P., Barr, C. L., Tischfield, J., Paschou, P., Heiman, G. A., & Georgitsi, M.
- Affiliations
- Democritus University of Thrace (GR)
- Rutgers, The State University of New Jersey (US)
- University of Catania (IT)
- Vadaskert Alapítvány a Gyermekek Lelki Egészségéért (HU)
- Sismanoglio General Hospital (GR)
- Semmelweis University (HU)
- University of Toronto (CA)
- University Health Network (CA)
- Corresponding author
- Heiman, Gary A.
- Georgitsi, Marianthi
- ORCID
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2016-09-21
- Volume
- 10
- Pages
- 428-428
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC5030307
- OpenAlex
- W2522515907
- Cited by
- 27
- References
- 68
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 6 · 2012: 1
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Funders
- Semmelweis Egyetem
- Magyar Tudományos Akadémia (BO/00987/16/5, /00987/16/5)
- National Institute of Mental Health (R01MH092293, U24MH068457)
- FP7 People: Marie-Curie Actions
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Tourette syndrome, candidate genes, rare variants, SLITRK1, BTBD9, serotonin transporter, targeted re-sequencing, linkage disequilibrium, obsessive-compulsive disorder, genetic susceptibility, European ancestry
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