1. Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.
- Author
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Huang, Alden Y., Yu, Dongmei, Davis, Lea K., Sul, Jae Hoon, Tsetsos, Fotis, Ramensky, Vasily, Zelaya, Ivette, Ramos, Eliana Marisa, Osiecki, Lisa, Chen, Jason A., McGrath, Lauren M., Illmann, Cornelia, Sandor, Paul, Barr, Cathy L., Grados, Marco, Singer, Harvey S., Nöthen, Markus M., Hebebrand, Johannes, King, Robert A., and Dion, Yves
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NEURAL circuitry , *TOURETTE syndrome , *MICROARRAY technology , *DELETION mutation , *DIAGNOSIS , *DISEASE risk factors - Abstract
Summary Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2.28, 95% CI [1.39–3.79], p = 1.2 × 10 −3 ) and known, pathogenic CNVs (OR = 3.03 [1.85–5.07], p = 1.5 × 10 −5 ). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk ( NRXN1 deletions, OR = 20.3, 95% CI [2.6–156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3–45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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