Association of AADAC Deletion and Gilles de la Tourette Syndrome in a Large European Cohort.

• Published in: Biological Psychiatry
• Main Authors: Bertelsen, Birgitte, Stefánsson, Hreinn, Riff Jensen, Lars, Melchior, Linea, Mol Debes, Nanette, Groth, Camilla, Skov, Liselotte, Werge, Thomas, Karagiannidis, Iordanis, Tarnok, Zsanett, Barta, Csaba, Nagy, Peter, Farkas, Luca, Brøndum-Nielsen, Karen, Rizzo, Renata, Gulisano, Mariangela, Rujescu, Dan, Kiemeney, Lambertus A, Tosato, Sarah, Nawaz, Muhammad Sulaman, Ingason, Andres, Unnsteinsdottir, Unnur, Steinberg, Stacy, Ludvigsson, Pétur, Stefansson, Kari, Kuss, Andreas Walter, Paschou, Peristera, Cath, Danielle, Hoekstra, Pieter J, Müller-Vahl, Kirsten, Stuhrmann, Manfred, Silahtaroglu, Asli, Pfundt, Rolph, Tümer, Zeynep
• Other Authors: 1 Rigshosp, Copenhagen Univ Hosp, Kennedy Ctr, Appl Human Mol Genet,Dept Clin Genet, Glostrup, Denmark 2 deCODE Genet, Reykjavik, Iceland 3 Univ Med Greifswald, Dept Human Genet, Greifswald, Germany 4 Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany 5 Herlev Hosp, Dept Pediat, Tourette Clin, DK-2730 Herlev, Denmark 6 Capital Reg Denmark, Mental Hlth Serv, Sct Hans, Inst Biol Psychiat,Mental Hlth Ctr, Hillerod, Denmark 7 Univ Copenhagen, Fac Med & Hlth Sci, Inst Clin Sci, Copenhagen, Denmark 8 IPSYCH, Initiat Integrat Psychiat Res, Roskilde, Denmark 9 Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece 10 Vadaskert Child & Adolescent Psychiat Clin, Budapest, Hungary 11 Semmelweis Univ, Mol Biol & Pathobiochem, Dept Med Chem, H-1085 Budapest, Hungary 12 Catania Univ, Dept Med & Pediat Sci, Sect Child Neuropsychiat, Catania, Italy 13 Univ Halle Wittenberg, Dept Psychiat, Psychotherapy & Psychosomat, D-06108 Halle, Germany 14 Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands 15 Univ Verona, Sect Psychiat, Dept Publ Hlth & Community Med, I-37100 Verona, Italy 16 Landspitalinn Univ Hosp, Dept Pediat, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital 17 Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands 18 Altrecht Acad Anxiety Outpatient Clin, Utrecht, Netherlands 19 Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands 20 Hannover Med Sch, Psychiat Clin, Social Psychiat & Psychotherapy, Hannover, Germany 21 Hannover Med Sch, Inst Human Genet, Hannover, Germany 22 Univ Copenhagen, Dept Cellular & Mol Med, Wilhelm Johansen Ctr Funct Genome Res, Copenhagen, Denmark 23 Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier Science Inc 2016
• Subjects: Tourette heilkenni; PED12; Tourette Syndrome; Catatonia; DNA Copy Number Variations; Genetic Association Studies; Iceland
• Online Access: http://hdl.handle.net/2336/607251; https://doi.org/10.1016/j.biopsych.2015.08.027

To access publisher's full text version of this article click on the hyperlink at the bottom of the page Gilles de la Tourette syndrome (GTS) is a complex neuropsychiatric disorder with a strong genetic influence where copy number variations are suggested to play a role in disease pathogenesis. In a previous small-scale copy number variation study of a GTS cohort (n = 111), recurrent exon-affecting microdeletions of four genes, including the gene encoding arylacetamide deacetylase (AADAC), were observed and merited further investigations. We screened a Danish cohort of 243 GTS patients and 1571 control subjects for submicroscopic deletions and duplications of these four genes. The most promising candidate gene, AADAC, identified in this Danish discovery sample was further investigated in cohorts from Iceland, the Netherlands, Hungary, Germany, and Italy, and a final meta-analysis, including a total of 1181 GTS patients and 118,730 control subjects from these six European countries, was performed. Subsequently, expression of the candidate gene in the central nervous system was investigated using human and mouse brain tissues. In the Danish cohort, we identified eight patients with overlapping deletions of AADAC. Investigation of the additional five countries showed a significant association between the AADAC deletion and GTS, and a final meta-analysis confirmed the significant association (p = 4.4 × 10(-4); odds ratio = 1.9; 95% confidence interval = 1.33-2.71). Furthermore, RNA in situ hybridization and reverse transcription-polymerase chain reaction studies revealed that AADAC is expressed in several brain regions previously implicated in GTS pathology. AADAC is a candidate susceptibility factor for GTS and the present findings warrant further genomic and functional studies to investigate the role of this gene in the pathogenesis of GTS. Lundbeck Foundation R24-A2419 R100-A9332 Tourette Syndrome Association USA, COST Action BM0905 Marie Curie Initial Training Networks TS-EUROTRAIN (FP7-PEOPLE) GA ...