# Collaborative Genomic Studies of Tourette Disorder Supplement

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $93,522

## Abstract

PROJECT SUMMARY
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 Neuron and in Cell Reports, identified two high confidence
and three probable novel TD risk genes, and collectively, pointed to neurite outgrowth and axon pathfinding as
potential pathological mechanisms5,6. More importantly, however, our findings demonstrated, for the first time, a
clear excess of de novo damaging point mutations and copy number variants (CNV) 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
1,000 simplex trios and make the phenotypic data and biological materials widely and rapidly available to the
broad scientific community; (2) accelerate gene and locus discovery, via whole exome sequencing (to identify
rare and/or de novo sequence variants) and genotyping (to identify rare and/or de novo CNVs) of these additional
TD trios, making these data rapidly and widely available as well (e.g. we have a long history of sharing our
genotyping data with the Psychiatric Genomics Consortium or PGC1 in order to facilitate common variant studies
of TD and related disorders); (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 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 and collaboration in rare variant human genomics and gene discovery.
Specifically, the proposal includes seven primary US sites, four direct subcontracts (two USA sites...

## Key facts

- **NIH application ID:** 10597813
- **Project number:** 3R01MH115961-05S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** SAMUEL KUPERMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $93,522
- **Award type:** 3
- **Project period:** 2018-06-10 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10597813

## Citation

> US National Institutes of Health, RePORTER application 10597813, Collaborative Genomic Studies of Tourette Disorder Supplement (3R01MH115961-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10597813. Licensed CC0.

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