# Large-scale collaborative genetic and epigenetic studies of Tourette Syndrome

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $648,187

## Abstract

PROJECT SUMMARY/ABSTRACT
Tourette Syndrome (TS) affects ~1% of children worldwide, and is three times more common in
boys than in girls. TS is one of the most highly heritable non-Mendelian neuropsychiatric
disorders. Although tics are the defining feature of TS, >85% of patients have additional
neuropsychiatric disorders, most notably obsessive-compulsive (OCD) and attention-deficit
hyperactivity disorder (ADHD), which are thought to be etiologically related, and which contribute
to the stigmatization and functional impairment commonly seen in TS patients. Abnormal
development and/or maintenance of cortico-striato-thalamo-cortical (CSTC) circuits is thought to
underlie the pathophysiology of TS and its comorbidities; however, the molecular and cellular
basis of the disorder, and the genetic relationships between TS, OCD, and ADHD, remain largely
elusive. Despite these challenges, the field of TS genetics is on the verge of accelerated gene
discovery, with multiple US and European consortia conducting genome-wide association studies
(GWAS) and copy number variant (CNV) analyses for TS in large patient cohorts. The team of
investigators leading this application represent all of the major TS consortia, and bring together
approximately 12,000 TS cases and 50,000 ancestry-matched controls. We will apply innovative
approaches to conduct large-scale GWAS and CNV meta and mega-analyses, with the goal of
identifying individual risk variants that lead to TS susceptibility, as well as elucidating the
underlying genetic architecture of the disorder and its comorbidities. We will then integrate the
resulting genomic data with functional epigenomic, transcriptomic, and neuro-imaging data to
determine the specific brain regions, cell types and neurodevelopmental time points where TS
susceptibility gene dysfunction leads to disease. We will also examine the role of biological sex
in the genetic underpinnings of TS. This integrative effort will utilize data spanning various fields
of neuroscience including neuro-genomics and neuro-epigenomics, neurodevelopmental biology,
and neuro-imaging. Our study will identify the tissues, cell types and circuits where aggregated
TS genetic risk is most highly concentrated, as well as the most relevant developmental period(s).
This spatio-temporal localization of TS pathogenesis at the molecular, cellular and circuit level will
provide critical information to guide the establishment of future disease models of TS and
potentially point to targets for new treatments.

## Key facts

- **NIH application ID:** 10101698
- **Project number:** 5R01NS105746-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Carol A Mathews
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $648,187
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101698

## Citation

> US National Institutes of Health, RePORTER application 10101698, Large-scale collaborative genetic and epigenetic studies of Tourette Syndrome (5R01NS105746-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10101698. Licensed CC0.

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