Journal article
Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach
European archives of psychiatry and clinical neuroscience, Vol.268(3), pp.301-316
05/29/2017
DOI: 10.1007/s00406-017-0808-8
PMCID: PMC5708161
PMID: 28555406
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.
Details
- Title: Subtitle
- Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach
- Creators
- Mohamed Abdulkadir - University Medical Center GroningenDouglas Londono - Rutgers, The State University of New JerseyDerek Gordon - Rutgers, The State University of New JerseyThomas V. Fernandez - Yale UniversityLawrence W. Brown - Children's Hospital of PhiladelphiaKeun-Ah Cheon - Yonsei UniversityBarbara J. Coffey - Icahn School of Medicine at Mount SinaiLonneke Elzerman - YuliusCarolin Fremer - Hochschule HannoverOdette Fründt - University Medical Center Hamburg-EppendorfBlanca Garcia-Delgar - Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic Universitari, Barcelona, SpainDonald L. Gilbert - Cincinnati Children's Hospital Medical CenterDorothy E. Grice - Icahn School of Medicine at Mount SinaiTammy Hedderly - Kings Health PartnersIsobel Heyman - UCL Institute of Child HealthHyun Ju Hong - Hallym University Sacred Heart HospitalChaim Huyser - De BasculeLaura Ibanez-Gomez - Icahn School of Medicine at Mount SinaiEwgeni Jakubovski - Hochschule HannoverYoung Key Kim - Yonsei UniversityYoung Shin Kim - University of California, San FranciscoYun-Joo Koh - Korea Institute for Children’s Social Development, Seoul, South KoreaSodahm Kook - Kangbuk Samsung HospitalSamuel Kuperman - Roy J. and Lucille A. Carver College of MedicineBennett Leventhal - University of California, San FranciscoAndrea G. Ludolph - Universität UlmMarcos Madruga-Garrido - Hospital Universitario Virgen del RocíoAthanasios Maras - Erasmus University RotterdamPablo Mir - Hospital Universitario Virgen del RocíoAstrid Morer - Centro de Investigación Biomédica en Red de Salud MentalKirsten Müller-Vahl - Hochschule HannoverAlexander Münchau - University of LübeckTara L. Murphy - UCL Institute of Child HealthKerstin J. Plessen - Mental Health ServicesVeit Roessner - Technische Universität DresdenEun-Young Shin - Yonsei UniversityDong-Ho Song - Yonsei UniversityJungeun Song - National Health Insurance Service Ilsan HospitalJennifer Tübing - University of LübeckEls van den Ban - Youth Division, Altrecht, Institute for Mental Health, Utrecht, The NetherlandsFrank Visscher - Admiraal De Ruyter ZiekenhuisSina Wanderer - Technische Universität DresdenMartin Woods - Kings Health PartnersSamuel H. Zinner - University of WashingtonRobert A. King - Yale UniversityJay A. Tischfield - Rutgers, The State University of New JerseyGary A. Heiman - Rutgers, The State University of New JerseyPieter J. Hoekstra - University Medical Center GroningenAndrea Dietrich - University Medical Center Groningen
- Resource Type
- Journal article
- Publication Details
- European archives of psychiatry and clinical neuroscience, Vol.268(3), pp.301-316
- DOI
- 10.1007/s00406-017-0808-8
- PMID
- 28555406
- PMCID
- PMC5708161
- NLM abbreviation
- Eur Arch Psychiatry Clin Neurosci
- ISSN
- 0940-1334
- eISSN
- 1433-8491
- Publisher
- Springer Berlin Heidelberg
- Grant note
- ; R01MH092290, R01MH092291, R01MH092292, R01MH092293, R01MH092513, R01MH092516, R01MH092520, R01MH092289, K08MH099424 / ; CVI-02526, CTS-7685 / ; PI-0741/2010, PI-0437-2012, PI-0471-2013 / ; MU 1692/3-1, MU 1692/4-1, project C5 of the SFB 936 / ; Informatics Starter Grant / ; PI10/01674, PI13/01461 / ;
- Language
- English
- Date published
- 05/29/2017
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293654502771
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