The Tourette International Collaborative Genetics (TIC Genetics) study, finding the genes causing Tourette syndrome: objectives and methods

Abstract

Tourette syndrome (TS) is a neuropsychiatric disorder characterised by motor and phonic tics and often accompanied by obsessive-compulsive disorder and attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet to be clarified fully. There is now mounting evidence that the genetic risks for TS include both common and rare variants and may involve complex multigenic inheritance or, in rare cases, a single major gene. Based on recent progress in many other common disorders with ostensibly similar genetic architectures, it is clear that large-scale patient cohorts and open-access repositories will be essential to further advance the field. To that end, the large multicenter Tourette International Collaborative Genetics (TIC Genetics) study was established. The goal of the TIC Genetics study is to undertake a comprehensive gene discovery effort, focusing both on familial genetic variants with large effects within multiply affected pedigrees and on de novo mutations ascertained through the analysis of apparently sporadic (non-familial) trios. The clinical data and biomaterials (DNA, transformed cell lines, RNA) are part of a sharing repository located within the National Institute for Mental Health Center for Collaborative Genetic Studies on Mental Disorders, USA, and will be made available to the broad scientific community. This resource will ultimately facilitate better understanding of the pathophysiology of TS and related disorders and the development of new therapies. Here, we describe the objectives and methods of the TIC Genetics study.

Histaminergic modulation in Tourette syndrome

“…This hypothesis is in line with evidence of altered structural connectivity within the cortico-striato-pallidothalamic circuitry [31]. As with other neurodevelopmental conditions, there is solid evidence for a genetic component to the expression of TS [32,33], thought to involve complex multigene changes [34]. TS has a heritability of approximately 0.58 [35] and its genetic heterogeneity has recently been confirmed by the results of recent large studies, which have failed to identify a single shared mutation or even common polymorphisms [36].…”

De Novo Coding Variants Are Strongly Associated with Tourette Disorder

“…Dietrich et al (2015) have previously described ascertainment and phenotyping of this cohort (Dietrich et al, 2015). We utilized the SeqCap EZ Human Exome v.2.0 library kit (Roche NimbleGen) to capture exomes from whole-blood-derived DNA and then sequenced with Illumina HiSeq 2000 technology.…”

“…Dietrich et al (2015) and Scharf et al (2013) have previously described recruitment criteria in detail for each group. Briefly, each of the parent-child trios recruited by TIC Genetics or TSAICG consisted of an affected child (proband) meeting criteria for TD or a chronic tic disorder based on the Diagnostic and Statistical Manual of Mental Disorders-Fourth edition, Text Revision (DSM-IV-TR) (American Psychiatric Association, 2000).…”

The inheritance of Tourette Disorder: A review

“…Recruitment is from more than twenty sites from the USA, Europe, and South Korea, and these materials are part of a sharing repository of the National Institute for Mental Health (NIMH) Center for Collaborative Genetic Studies on Mental Disorders. Data and biomaterials will be made available to the widest possible research community to hasten the identification of causal genetic factors and facilitate better understanding and treatment of TD 66 . Both consortia, TSAICG and TIC Genetics, are currently working closely to plan complementary analyses and to combine existing data for analyses of larger TD data sets.…”