Tourette disorder and other tic disorders.

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Tourette disorder is a developmental neuropsychiatric condition characterized by motor and vocal tics.
• It affects an estimated 0.5-0.7% of the population and is part of a spectrum of tic disorders.
• Genetic factors are strongly implicated in Tourette disorder risk, yet specific causal variants remain elusive.

Purpose of the Study:

• To review the challenges and expected progress in identifying genetic variants associated with Tourette disorder.
• To discuss the likely complex genetic architecture of Tourette disorder.

Main Methods:

• Review of existing literature on genetic association studies (candidate gene and GWAS) for Tourette disorder.
• Discussion of findings from rare mutation studies.
• Consideration of polygenic models involving common and rare variants.

Main Results:

• Candidate gene studies have yielded non-replicable findings.
• Genome-wide association studies (GWAS) have lacked sufficient sample sizes for significant discoveries.
• Rare mutations have been identified, but their direct causality is difficult to ascertain.

Conclusions:

• Tourette disorder likely results from a combination of common, low-effect genetic variants and rare, larger-effect variants interacting with environmental factors.
• Larger patient cohorts and advances in high-throughput sequencing are expected to accelerate genetic discoveries for Tourette disorder.