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
Abstract
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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