Rare copy number variants in NRXN1 and CNTN6 increase risk for Tourette syndrome

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 Noethen; Johannes Hebebrand; Robert A King; Yves Dion; Guy Rouleau; Cathy L Budman; Christel Depienne; Yulia Worbe; Andreas Hartmann; Kirsten R Muller-Vahl; Manfred Stuhrmann; Harald Aschauer; Mara Stamenkovic; Monika Schloegelhofer; Anastasios Konstantinidis; Gholson L Lyon; William M McMahon; Csaba Barta; Zsanett Tarnok; Peter Nagy; James R Batterson; Renata Rizzo; Danielle C Cath

doi:10.1101/062471

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bioRxiv · 10.1101/062471

Rare copy number variants in NRXN1 and CNTN6 increase risk for Tourette syndrome

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Abstract

Tourette syndrome (TS) is highly heritable, although identification of its underlying genetic cause(s) has remained elusive. We examined a European ancestry sample composed of 2,435 TS cases and 4,100 controls for copy-number variants (CNVs) using SNP microarrays and identified two genome-wide significant loci that confer a substantial increase in risk for TS (NRXN1, OR=20.3, 95%CI [2.6-156.2], p=6.0 x 10-6; CNTN6, OR=10.1, 95% CI [2.3-45.4], p=3.7 x 10-5). Approximately 1% of TS cases carried one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS.

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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 Noethen, Johannes Hebebrand, Robert A King, Yves Dion, Guy Rouleau, Cathy L Budman, Christel Depienne, Yulia Worbe, Andreas Hartmann, Kirsten R Muller-Vahl, Manfred Stuhrmann, Harald Aschauer, Mara Stamenkovic, Monika Schloegelhofer, Anastasios Konstantinidis, Gholson L Lyon, William M McMahon, Csaba Barta, Zsanett Tarnok, Peter Nagy, James R Batterson, Renata Rizzo, Danielle C Cath. 2016-07-08. Rare copy number variants in NRXN1 and CNTN6 increase risk for Tourette syndrome. https://doi.org/10.1101/062471

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