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

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 KimYoung 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

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)301-316
Number of pages16
JournalEuropean Archives of Psychiatry and Clinical Neuroscience
Volume268
Issue number3
DOIs
StatePublished - Apr 1 2018
Externally publishedYes

Keywords

  • Attention-deficit/hyperactivity disorder
  • Candidate gene study
  • Obsessive–compulsive disorder
  • Tourette syndrome
  • Transmission Disequilibrium Test

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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