Association of AADAC Deletion and Gilles de la Tourette Syndrome in a Large European Cohort
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Association of AADAC Deletion and Gilles de la Tourette Syndrome in a Large European Cohort. / Bertelsen, Birgitte; Stefánsson, Hreinn; Riff Jensen, Lars; Melchior, Linea; Debes, Nanette Mol; 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, Andrés; 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.
In: Biological Psychiatry, Vol. 79, No. 5, 01.03.2016, p. 383–391.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Association of AADAC Deletion and Gilles de la Tourette Syndrome in a Large European Cohort
AU - Bertelsen, Birgitte
AU - Stefánsson, Hreinn
AU - Riff Jensen, Lars
AU - Melchior, Linea
AU - Debes, Nanette Mol
AU - Groth, Camilla
AU - Skov, Liselotte
AU - Werge, Thomas
AU - Karagiannidis, Iordanis
AU - Tarnok, Zsanett
AU - Barta, Csaba
AU - Nagy, Peter
AU - Farkas, Luca
AU - Brøndum-Nielsen, Karen
AU - Rizzo, Renata
AU - Gulisano, Mariangela
AU - Rujescu, Dan
AU - Kiemeney, Lambertus A
AU - Tosato, Sarah
AU - Nawaz, Muhammad Sulaman
AU - Ingason, Andrés
AU - Unnsteinsdottir, Unnur
AU - Steinberg, Stacy
AU - Ludvigsson, Pétur
AU - Stefansson, Kari
AU - Kuss, Andreas Walter
AU - Paschou, Peristera
AU - Cath, Danielle
AU - Hoekstra, Pieter J
AU - Müller-Vahl, Kirsten
AU - Stuhrmann, Manfred
AU - Silahtaroglu, Asli
AU - Pfundt, Rolph
AU - Tümer, Zeynep
N1 - Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.
AB - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.
U2 - 10.1016/j.biopsych.2015.08.027
DO - 10.1016/j.biopsych.2015.08.027
M3 - Journal article
C2 - 26444075
VL - 79
SP - 383
EP - 391
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 5
ER -
ID: 153610198