Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Neuron. 2017 Jun 21;94(6):1101-1111.e7. doi: 10.1016/j.neuron.2017.06.010.

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

Author information

1
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
2
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
3
Division of Genetic Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
4
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
5
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
6
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA; Moscow Institute of Physics and Technology, Dolgoprudny, Institusky 9, Moscow 141701, Russian Federation.
7
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA.
8
Department of Psychology, University of Denver, Denver, CO 80210, USA.
9
Toronto Western Research Institute, University Health Network and Youthdale Treatment Centres, University of Toronto, Toronto, ON M5T 2S8, Canada.
10
Krembil Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada.
11
Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
12
Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany; Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany.
13
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
14
Yale Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
15
University of Montréal, Montréal, QC H3T 1J4, Canada.
16
Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada.
17
Hofstra Northwell School of Medicine, Hempstead, NY 11549, USA.
18
IGBMC, CNRS UMR 7104/INSERM U964/Université de Strasbourg, 67404 Illkirch Cedex, France; Brain and Spine Institute, UPMC/INSERM UMR_S1127, 75013 Paris Cedex 05, France.
19
Brain and Spine Institute, UPMC/INSERM UMR_S1127, 75013 Paris Cedex 05, France.
20
Clinic of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, 30625 Hannover, Germany.
21
Institute of Human Genetics, Hannover Medical School, 30625 Hannover, Germany.
22
Department of Psychiatry and Psychotherapy, Medical University Vienna, 1090 Vienna, Austria; Biopsychosocial Corporation, 1090 Vienna, Austria.
23
Department of Psychiatry and Psychotherapy, Medical University Vienna, 1090 Vienna, Austria.
24
Department of Psychiatry and Psychotherapy, Medical University Vienna, 1090 Vienna, Austria; Center for Mental Health Muldenstrasse, BBRZMed, 4020 Linz, Austria.
25
Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
26
Department of Psychiatry, University of Utah, Salt Lake City, UT 84108, USA.
27
Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, 1085 Budapest, Hungary.
28
Vadaskert Child and Adolescent Psychiatric Hospital, 1021 Budapest, Hungary.
29
Children's Mercy Hospital, Kansas City, KS 64108, USA.
30
Dipartimento di Medicina Clinica e Sperimentale, Università di Catania, 95131 Catania, Italy.
31
Department of Psychiatry, University Medical Center Groningen & Drenthe Mental Health Center, 9700 RB Groningen, the Netherlands; Department of Clinical Psychology, Utrecht University, 3584 CS Utrecht, the Netherlands.
32
Department of Child Psychiatry, Medical University of Warsaw, 00-001 Warsaw, Poland.
33
Penn State University College of Medicine, Hershey, PA 17033, USA.
34
Department of Neurology and Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL 32607, USA.
35
Marquette University, Milwaukee, WI 53233, USA; University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA.
36
Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff CF24 4HQ, Wales, UK.
37
SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.
38
Department of Psychiatry & Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
39
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, 1081 HV Amsterdam, the Netherlands.
40
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
41
Department of Psychiatry, Genetics Institute, University of Florida, Gainesville, FL 32611, USA.
42
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: jscharf@partners.org.
43
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: gcoppola@ucla.edu.

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.

KEYWORDS:

CNTN6; NRXN1; Tourette Syndrome; copy number variation; genetics; neurodevelopmental disorders; structural variation; tic disorders

PMID:
28641109
PMCID:
PMC5568251
DOI:
10.1016/j.neuron.2017.06.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center