Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome

Huang, A. Y., Yu, D., Davis, L. K., Sul, J. H., Tsetsos, F., Ramensky, V., Zelaya, I., Ramos, E. M., Osiecki, L., Chen, J. A., McGrath, L. M., Illmann, C., Sandor, P., Barr, C. L., Grados, M., Singer, H. S., Nothen, M. M., Hebebrand, J., King, R. A., Dion, Y., Rouleau, G., Budman, C. L., Depienne, C., Worbe, Y., Hartmann, A., Muller-Vahl, K. R., Stuhrmann, M., Aschauer, H., Stamenkovic, M., Schloegelhofer, M., Konstantinidis, A., Lyon, G. J., McMahon, W. M., Barta, C., Tarnok, Z., Nagy, P., Batterson, J. R., Rizzo, R., Cath, D. C., Wolanczyk, T., Berlin, C., Malaty, I. A., Okun, M. S., Woods, D. W., Rees, E., Pato, C. N., Pato, M. T., Knowles, J. A., Posthuma, D., Pauls, D. L., Cox, N. J., Neale, B. M., Freimer, N. B., Paschou, P., Mathews, C. A., Scharf, J. M., Coppola, G. (June 2017) Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome. Neuron, 94 (6). 1101-1111.e7. ISSN 0896-6273

URL: https://www.ncbi.nlm.nih.gov/pubmed/28641109
DOI: 10.1016/j.neuron.2017.06.010


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 x 10-3) and known, pathogenic CNVs (OR = 3.03 [1.85-5.07], p = 1.5 x 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.

Item Type: Paper
Uncontrolled Keywords: Cntn6 Nrxn1 Tourette Syndrome copy number variation genetics neurodevelopmental disorders structural variation tic disorders
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > copy number variants
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
diseases & disorders > mental disorders > Tourette Syndrome
CSHL Authors:
Communities: CSHL labs > Lyon lab
Depositing User: Matt Covey
Date: 21 June 2017
Date Deposited: 29 Jun 2017 21:00
Last Modified: 06 Jul 2021 19:30
PMCID: PMC5568251
Related URLs:
URI: https://repository.cshl.edu/id/eprint/35039

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