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Exploring the contribution of non-coding and somatic copy number variations to the Tourette Disorder

Award Number: R03NS148680
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/18/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Exploring the contribution of non-coding and somatic copy number variations to the Tourette Disorder - Abstract Tourette disorder (TS) affects approximately 1 in 150 children and exhibits one of the highest familial recurrence rates among neuropsychiatric disorders. Despite this, previous genome-wide association and exome sequencing studies have identified only a limited number of risk genes and rare copy number variants (CNVs), suggesting that key genetic contributors may lie in non-coding regions or in somatic genomic alterations. This project aims to investigate two underexplored contributors to TS genetics: germline non-coding regulatory variants and somatic CNVs. Leveraging SNP array and whole genome sequencing (WGS) data from large cohort, we will conduct a comprehensive analysis to elucidate their roles in TS etiology. Aim 1 will assess the contribution of germline non-coding variants by analyzing imputed SNP array data from 7,418 TS cases and WGS data from 52 TS brains. Variants will be mapped to cell type–specific regulatory regions identified through single-cell ATAC- seq analysis of postmortem TS brains affecting transcription factor binding sites (TFBS). We will compare the burden and predicted functional effects of these variants between TS and control groups. Aim 2 will investigate somatic CNVs in the same cohort using CNVpytor, a state-of-the-art tool for detecting somatic CNVs from SNP array and WGS data. We will compare CNV frequency, size, and genomic location between TS and control samples to identify TS-associated somatic alterations. By integrating analyses of non-coding and somatic variations, this project will provide the first large-scale assessment of these genetic mechanisms in TS, offering novel insights into its molecular basis and potential therapeutic targets.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $161,400 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/17/2026	NEW	$161,400
														Subtotal = $161,400

Grand Total All Awards = $161,400

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Exploring the contribution of non-coding and somatic copy number variations to the Tourette Disorder

Award Number: R03NS148680

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/18/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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