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 Noethen, Johannes Hebebrand, Robert A. King, Yves DionGuy Rouleau, Cathy L. Budman, Christel Depienne, Yulia Worbe, Andreas Hartmann, Kirsten R. Mueller-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, TSAICG, Gilles Tourette Syndrome GWAS

    OnderzoeksoutputAcademicpeer review

    116 Citaten (Scopus)


    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 Mb), singleton events (OR = 2.28, 95% CI [1.39-3.79], p = 1.2310(-3)) and known, pathogenic CNVs (OR = 3.03 [1.85-5.07], p = 1.5 3 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.

    Originele taal-2English
    Pagina's (van-tot)1101-+
    Aantal pagina's18
    Nummer van het tijdschrift6
    StatusPublished - 21-jun.-2017

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