Title |
Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome
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Published in |
Neuron, June 2017
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DOI | 10.1016/j.neuron.2017.06.010 |
Pubmed ID | |
Authors |
Alden Y. Huang, Dongmei Yu, Lea K. Davis, Jae Hoon Sul, Fotis Tsetsos, Vasily Ramensky, Ivette Zelaya, Eliana Marisa Ramos, Lisa Osiecki, Jason A. Chen, Lauren M. McGrath, Cornelia Illmann, Paul Sandor, Cathy L. Barr, Marco Grados, Harvey S. Singer, Markus M. Nöthen, Johannes Hebebrand, Robert A. King, Yves Dion, Guy Rouleau, Cathy L. Budman, Christel Depienne, Yulia Worbe, Andreas Hartmann, Kirsten R. Müller-Vahl, Manfred Stuhrmann, Harald Aschauer, Mara Stamenkovic, Monika Schloegelhofer, Anastasios Konstantinidis, Gholson J. Lyon, William M. McMahon, Csaba Barta, Zsanett Tarnok, Peter Nagy, James R. Batterson, Renata Rizzo, Danielle C. Cath, Tomasz Wolanczyk, Cheston Berlin, Irene A. Malaty, Michael S. Okun, Douglas W. Woods, Elliott Rees, Carlos N. Pato, Michele T. Pato, James A. Knowles, Danielle Posthuma, David L. Pauls, Nancy J. Cox, Benjamin M. Neale, Nelson B. Freimer, Peristera Paschou, Carol A. Mathews, Jeremiah M. Scharf, Giovanni Coppola, The Tourette Syndrome Association International Consortium for Genetics, Ruth D. Bruun, Sylvain Chouinard, Sabrina Darrow, Erica Greenberg, Matthew E. Hirschtritt, The Gilles de la Tourette Syndrome GWAS Replication Initiative, Roger Kurlan, James F. Leckman, Mary M. Robertson, Jan Smit |
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 × 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 20 | 54% |
United Kingdom | 2 | 5% |
Netherlands | 1 | 3% |
Belgium | 1 | 3% |
Taiwan | 1 | 3% |
Hungary | 1 | 3% |
Ireland | 1 | 3% |
India | 1 | 3% |
Uzbekistan | 1 | 3% |
Other | 0 | 0% |
Unknown | 8 | 22% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 23 | 62% |
Scientists | 10 | 27% |
Practitioners (doctors, other healthcare professionals) | 2 | 5% |
Science communicators (journalists, bloggers, editors) | 1 | 3% |
Unknown | 1 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | <1% |
Sweden | 1 | <1% |
Unknown | 160 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 23 | 14% |
Researcher | 19 | 12% |
Student > Bachelor | 19 | 12% |
Student > Doctoral Student | 14 | 9% |
Student > Postgraduate | 10 | 6% |
Other | 31 | 19% |
Unknown | 46 | 28% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 26 | 16% |
Medicine and Dentistry | 23 | 14% |
Neuroscience | 22 | 14% |
Agricultural and Biological Sciences | 20 | 12% |
Psychology | 7 | 4% |
Other | 14 | 9% |
Unknown | 50 | 31% |