Genomic Studies of Gilles de la Tourette Syndrome

This study consists of three components.

The first component includes genome-wide association study (GWAS) data on 695 TS cases and 198 ancestry matched controls from the first TS GWAS of 1285 TS cases and 4964 ancestry matched controls.

The second component includes genome-wide association study (GWAS) data on 2106 TS cases from the second TS GWAS of 2716 TS cases and 3762 ancestry matched controls.

The third component consists of 438 individuals representing 146 probands with DSM-IV-TR diagnosed Tourette Syndrome and their parents (146 complete parent-offspring trios). These individuals are part of the whole exome sequencing study, aiming to use whole exome sequencing of TS parent-offspring to identify de novo protein-truncating variants (PTVs) that are present in the child with TS but not in either parent.

All subjects were collected by the Tourette Association of America International Consortium for Genetics (TAAICG) at seven sites in the United States and Canada.

Both affected individuals and unaffected relatives were assessed for the presence of Tourette Syndrome and Chronic (Persistent) Tic Disorder (CTD) using a standardized, semi-structured interview, which has high clinical validity and reliability for the diagnoses of TS and CTD (TSAICG, Am J Hum Genet, 2007 (PMID: 17304708)); Darrow et al., Psychiatric Research, 2015 (PMID: 26054936)).

• Study Design:
  • Family/Twin/Trios
• Study Type:
  • Case-Control
  • Parent-Offspring Trios
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 3296
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• Sequence Read Archive
• BioSample
• MeSH
• Gene
• PMC

The cases were required a TS Classification Study Group (TSCSG) diagnosis of definite TS (a DSM-IV-TR diagnosis of TS plus tics observed by an experienced clinician), and available genomic DNA extracted either from blood or cell lines. The exclusion criteria consisted of a history of intellectual disability (ID), tardive tourettism, or other known genetic, metabolic or acquired tic disorders.

The 198 French Canadian controls were collected in parallel with the French Canadian cases. They were unselected, ancestry matched controls.

Parent-offspring trios were required to have a child proband with a DSM-IV-TR diagnosis of Tourette Syndrome (TS). Trios were preferentially selected for parents without diagnoses of TS or Chronic Tic Disorder (CTD), though trios were not excluded if either (or both) parents had TS or CT. Trios were excluded if a child was known to have intellectual disability, an autism spectrum disorder, psychosis or seizures, though these diagnoses were not formally assessed in all families.

1994-2014: Samples collected
2009-2010: High-density SNP genotyping on initial case-control GWAS sample
2012-2014: High-density SNP genotyping on follow-up case-control GWAS sample
2014: Whole-exome sequencing performed on 186 parent-offspring trios

• Primary Phenotype: Tourette Syndrome
• Tics
• Neurodevelopmental Disorders

• NRXN1
• CNTN6
• COL27A1
• LINC01122

• Principal Investigators
  • Jeremiah M. Scharf, MD, PhD. Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Departments of Neurology and Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Carol A. Mathews, MD. Center for OCD, Anxiety and Related Disorders, Genetic Institute, Department of Psychiatry, University of Florida, Gainesville, FL, USA.
  • Giovanni Coppola, MD. Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
• Institute
  • National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA.
• Funding Sources
  • U01 NS40024-09S1. National Institutes of Health, Bethesda, MD, USA.
  • K02 NS85048. National Institutes of Health, Bethesda, MD, USA.
  • P30 NS062691. National Institutes of Health, Bethesda, MD, USA.
  • U01 NS40024. National Institutes of Health, Bethesda, MD, USA.
  • R01 NS016648. National Institutes of Health, Bethesda, MD, USA.
  • Tourette Association of America, Bayside, NY, USA.