# 4/7-Collaborative genomic studies of Tourette Disorder

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $213,771

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite strong evidence for a genetic contribution to Tourette disorder (TD), progress in the identification of
specific risk genes has been, until quite recently, halting. However, building upon NIMH’s support for our initial
efforts to ascertain TD trios as well as our highly successful experience with genomic investigations of autism
spectrum disorders (ASD), we have now demonstrated a clear path forward for reliable, systematic gene
discovery in TD. Our TD work, recently published in the journal Neuron, identified one high confidence and
three probable novel TD risk genes collectively pointing to neurite outgrowth and axon pathfinding as potential
pathological mechanisms1. More importantly, however, our findings demonstrate, for the first time, a clear
excess of de novo damaging point mutations in individuals with TD, with effect sizes that rival our recent
findings in ASD. This discovery strongly suggests that sequencing of larger cohorts will reliably and rapidly
lead to the identification of many more highly penetrant risk genes. Moreover, our recent work suggests an
increased yield of highly penetrant damaging de novo variants in probands who are affected both with TD and
obsessive compulsive disorder or attention deficit hyperactivity disorder, suggesting that our efforts may well
also offer avenues to study the overlap in genetic risks for these often-comorbid conditions. Our current
application proposes to: (1) expand our well characterized TD trio cohort by an additional 1,025 simplex trios
and make the phenotypic data and biological materials widely and rapidly available to the broad scientific
community; (2) accelerate gene discovery, via genotyping (for large de novo CNV identification) and whole
exome sequencing (for de novo single nucleotide variant, insertion/deletion variant, and small CNV
identification) of these additional TD trios, making these data rapidly and widely available as well; (3) extend
the process of in silico and in vitro genomics investigations to elaborate the biology of TD with the long term
goal of developing novel and more effective treatment strategies; and (4) begin biological characterization of
TD variants using iPSC-derived neuronal cells. Given the potentially debilitating nature of TD alone, and a
population prevalence of approximately 1 in 100 individuals, such advances would confer a significant public
health benefit. The study design again rests heavily on the collaborative R01 mechanism that will bring
together deep experience with the TD phenotype at multiple sites across the globe with scientists with a strong
track record of success in rare variant human genomics and gene discovery. Specifically, the proposal includes
seven primary US sites, three direct subcontracts (one USA site for clinical supervision and two foreign
coordinating sites), and fourteen secondary clinical sites within Europe and South Korea.

## Key facts

- **NIH application ID:** 10598206
- **Project number:** 3R01MH115962-05S1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** DONALD L GILBERT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $213,771
- **Award type:** 3
- **Project period:** 2018-06-10 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10598206

## Citation

> US National Institutes of Health, RePORTER application 10598206, 4/7-Collaborative genomic studies of Tourette Disorder (3R01MH115962-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10598206. Licensed CC0.

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