# Integrating Common and Rare Variation to Discover Genes Associated with Tourette Syndrome

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $956,462

## Abstract

Integrating Common and Rare Variation to Discover Genes Associated with Tourette Syndrome
Tourette Syndrome (TS) is a childhood-onset, neuropsychiatric disorder that is highly heritable, though
discovery of definitive TS susceptibility genes has been challenging. This multi-PD/PI application, which aims
to identify new susceptibility genes for TS and to examine their relationship to clinical disease outcomes,
continues the work of the Tourette Association of America International Consortium for Genetics (TAAICG), the
longest standing research collaborative group dedicated to understanding the genetic causes underlying TS.
The research plan consists of: 1) Whole exome sequencing of 1,400 TS parent-proband trios to identify rare,
potentially deleterious genetic variants of relevance to TS; 2) Genome-wide analyses of de novo copy-number
variation (CNVs) in these 1,400 TS trios to identify high impact, rare structural variation associated with TS;
3) Use of information about TS-relevant common variation from existing genome-wide association study
(GWAS) data on 4,819 TS cases and 9,488 controls to prioritize a subset of 800 of the 1,400 TS trios for
cryptic structural variation sequencing studies to capture de novo gene-disrupting chromosomal
rearrangements not detectable by standard techniques; and 4) Integration of identified rare and common
variation to develop prediction models of disease outcome, including tic severity, functional impairment, tic
persistence into adulthood, and psychiatric comorbidity.
The proposed study will be conducted at Massachusetts General Hospital, University of Florida, University of
California at Los Angeles, and Vanderbilt University Medical Center, each who have complementary expertise
in computational biology, analysis of next-generation sequencing data, and integration of disease-associated
DNA variation with clinical data. This proposal provides a unique and exciting opportunity to rapidly advance
the goal of identifying the biological basis of this complex and important model neuropsychiatric disorder which
in the future could lead to prediction of disease severity and to targeted treatments and/or prevention.

## Key facts

- **NIH application ID:** 10359202
- **Project number:** 5R01NS102371-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Carol A Mathews
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $956,462
- **Award type:** 5
- **Project period:** 2018-03-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359202

## Citation

> US National Institutes of Health, RePORTER application 10359202, Integrating Common and Rare Variation to Discover Genes Associated with Tourette Syndrome (5R01NS102371-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10359202. Licensed CC0.

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