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This study identified new genetic risk factors for Tourette Syndrome (TS) and Persistent Tic Disorder (PTD) by analyzing copy number variants (CNVs). A novel duplication at 17q12 was significantly associated with these neurodevelopmental conditions.

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Area of Science:

  • Genetics
  • Neuroscience
  • Medical Genetics

Background:

  • Tourette Syndrome (TS) and Persistent Tic Disorder (PTD) are heritable childhood-onset neuropsychiatric disorders.
  • Identifying specific genetic risk factors for TS/PTD has been limited by sample sizes in previous studies.

Purpose of the Study:

  • To increase the sample size for copy number variant (CNV) analysis in TS/PTD.
  • To identify novel genetic loci associated with TS/PTD through a meta-analysis of genomic data.

Main Methods:

  • Conducted a meta-analysis of microarray CNV data from three TS/PTD genomics consortia.
  • Supplemented existing data with new data from 3,291 cases, resulting in a total of 5,725 cases and 10,982 controls.
  • Performed genome-wide analysis to identify significant CNV associations.

Main Results:

  • TS/PTD cases showed a higher burden of ultra-rare deletions in intolerant genes (OR=1.68) and carried more established neurodevelopmental CNVs (OR=1.42).
  • A novel, genome-wide significant CNV locus was discovered at 17q12, involving duplications.
  • A specific ~1.4 Mb duplication at 17q12 was found in eight cases, and a smaller duplication including the *ACACA* gene was found in one case.

Conclusions:

  • Rare, genic CNVs significantly contribute to the genetic architecture of TS/PTD.
  • Identified a new genome-wide significant association for TS/PTD with duplications at the 17q12 locus.