From Genetics to Epigenetics: New Perspectives in Tourette Syndrome Research.

Luca Pagliaroli,Borbála Vető,Csaba Barta,Tamás Arányi

doi:10.3389/fnins.2016.00277

Abstract

Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder marked by the appearance of multiple involuntary motor and vocal tics. TS presents high comorbidity rates with other disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). TS is highly heritable and has a complex polygenic background. However, environmental factors also play a role in the manifestation of symptoms. Different epigenetic mechanisms may represent the link between these two causalities. Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome. This review provides a summary of the recent findings in genetic background of TS, followed by an overview on different epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs in the regulation of gene expression. Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date. Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS.

Highlights

Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by one vocal and multiple motor tics, lasting longer than a year (Robertson, 2000)
A replication study with the top 42 single nucleotide polymorphisms (SNPs) of the original genome-wide association study (GWAS) was performed with a sample of over 600 cases and 600 controls and the meta-analysis yielded a top signal at rs2060546 with p = 5.8∗10−7 in proximity of the NTN4 gene on chromosome 12q22, which codes for netrin 4, an axon guidance protein expressed in the developing striatum
The results suggest that the 2 repeat allele might play a protective role, while the common 4 repeat may predispose to TS (Liu et al, 2014)

Summary

Introduction

Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by one vocal and multiple motor tics, lasting longer than a year (Robertson, 2000). A replication study with the top 42 SNPs of the original GWAS was performed with a sample of over 600 cases and 600 controls and the meta-analysis yielded a top signal at rs2060546 with p = 5.8∗10−7 in proximity of the NTN4 gene on chromosome 12q22, which codes for netrin 4, an axon guidance protein expressed in the developing striatum.

Results

Conclusion