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Published in: European Archives of Psychiatry and Clinical Neuroscience 3/2018

Open Access 01-04-2018 | Original Paper

Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach

Authors: Mohamed Abdulkadir, Douglas Londono, Derek Gordon, Thomas V. Fernandez, Lawrence W. Brown, Keun-Ah Cheon, Barbara J. Coffey, Lonneke Elzerman, Carolin Fremer, Odette Fründt, Blanca Garcia-Delgar, Donald L. Gilbert, Dorothy E. Grice, Tammy Hedderly, Isobel Heyman, Hyun Ju Hong, Chaim Huyser, Laura Ibanez-Gomez, Ewgeni Jakubovski, Young Key Kim, Young Shin Kim, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett Leventhal, Andrea G. Ludolph, Marcos Madruga-Garrido, Athanasios Maras, Pablo Mir, Astrid Morer, Kirsten Müller-Vahl, Alexander Münchau, Tara L. Murphy, Kerstin J. Plessen, Veit Roessner, Eun-Young Shin, Dong-Ho Song, Jungeun Song, Jennifer Tübing, Els van den Ban, Frank Visscher, Sina Wanderer, Martin Woods, Samuel H. Zinner, Robert A. King, Jay A. Tischfield, Gary A. Heiman, Pieter J. Hoekstra, Andrea Dietrich

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 3/2018

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Abstract

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent–child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case–control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive–compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.
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Metadata
Title
Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach
Authors
Mohamed Abdulkadir
Douglas Londono
Derek Gordon
Thomas V. Fernandez
Lawrence W. Brown
Keun-Ah Cheon
Barbara J. Coffey
Lonneke Elzerman
Carolin Fremer
Odette Fründt
Blanca Garcia-Delgar
Donald L. Gilbert
Dorothy E. Grice
Tammy Hedderly
Isobel Heyman
Hyun Ju Hong
Chaim Huyser
Laura Ibanez-Gomez
Ewgeni Jakubovski
Young Key Kim
Young Shin Kim
Yun-Joo Koh
Sodahm Kook
Samuel Kuperman
Bennett Leventhal
Andrea G. Ludolph
Marcos Madruga-Garrido
Athanasios Maras
Pablo Mir
Astrid Morer
Kirsten Müller-Vahl
Alexander Münchau
Tara L. Murphy
Kerstin J. Plessen
Veit Roessner
Eun-Young Shin
Dong-Ho Song
Jungeun Song
Jennifer Tübing
Els van den Ban
Frank Visscher
Sina Wanderer
Martin Woods
Samuel H. Zinner
Robert A. King
Jay A. Tischfield
Gary A. Heiman
Pieter J. Hoekstra
Andrea Dietrich
Publication date
01-04-2018
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Psychiatry and Clinical Neuroscience / Issue 3/2018
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-017-0808-8

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