Genetics of Tourette Syndrome

Abstract

Tourette syndrome (TS) is a developmental neuropsychiatric disorder that is characterized by vocal and motor tics and is estimated to affect 0.2–1 % of the population. Despite evidence for a substantial genetic contribution toward dis- ease risk, identifi cation and replication of associations between genetic variants and TS have been challenging. Rare mutations in several genes have been identifi ed, yet it is unclear whether these genes or their biological pathways play a role in the majority of TS cases. Similar to other complex neuropsychiatric disorders, it is likely that multiple variations in multiple genes, both within the individual and the population, may act together with environmental factors to confer risk. Centralized consortia are collecting larger patient cohorts required to identify candidate genes and biological pathways for TS. Recent profi ling of gene expression in the striatum, a brain region highly implicated in TS, indicates downregulation of GABAergic and cholinergic interneurons and shows overlap with gene networks implicated by rare structural genetic variants. Together, integrated analyses of common and rare sequence and structural variation, transcriptomic variation, and bioinformatic analyses of convergent gene networks and pathways may elucidate the genetic etiology of TS.