title: The Genetic Etiology of Tourette Syndrome: Large-Scale Collaborative Efforts on the Precipice of Discovery.
abstract: Gilles de la Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder that is characterized by multiple motor and phonic tics. It has a complex etiology with multiple genes likely interacting with environmental factors to lead to the onset of symptoms. The genetic basis of the disorder remains elusive. However, multiple resources and large-scale projects are coming together, launching a new era in the field and bringing us on the verge of discovery. The large-scale efforts outlined in this report are complementary and represent a range of different approaches to the study of disorders with complex inheritance. The Tourette Syndrome Association International Consortium for Genetics (TSAICG) has focused on large families, parent-proband trios and cases for large case-control designs such as genomewide association studies (GWAS), copy number variation (CNV) scans, and exome/genome sequencing. TIC Genetics targets rare, large effect size mutations in simplex trios, and multigenerational families. The European Multicentre Tics in Children Study (EMTICS) seeks to elucidate gene-environment interactions including the involvement of infection and immune mechanisms in TS etiology. Finally, TS-EUROTRAIN, a Marie Curie Initial Training Network, aims to act as a platform to unify large-scale projects in the field and to educate the next generation of experts. Importantly, these complementary large-scale efforts are joining forces to uncover the full range of genetic variation and environmental risk factors for TS, holding great promise for identifying definitive TS susceptibility genes and shedding light into the complex pathophysiology of this disorder.
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of ThraceAlexandroupoli, Greece; Department of Medicine, Aristotle University of ThessalonikiThessaloniki, Greece.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Georgitsi
authors.affiliation: Department of Psychiatry, University of California, San Francisco San Francisco, CA, USA.
authors.forename: A Jeremy
authors.initials: AJ
authors.lastname: Willsey
authors.affiliation: Department of Psychiatry, University of Florida School of Medicine Gainesville, FL, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Mathews
authors.affiliation: Department of Psychiatry, University of California, San Francisco San Francisco, CA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: State
authors.affiliation: Departments of Neurology and Psychiatry, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
authors.forename: Jeremiah M
authors.initials: JM
authors.lastname: Scharf
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace Alexandroupoli, Greece.
authors.forename: Peristera
authors.initials: P
authors.lastname: Paschou
keywords: GWAS (genomewide association study); Gilles de la Tourette syndrome; collaborative studies; gene-environment interactions; genetics of complex disorders; neurodevelopmental disorders; next generation sequencing