Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study


Por: McGrath L.M., Yu D., Marshall C., Davis L.K., Thiruvahindrapuram B., Li B., Cappi C., Gerber G., Wolf A., Schroeder F.A., Osiecki L., O'Dushlaine C., Kirby A., Illmann C., Haddad S., Gallagher P., Fagerness J.A., Barr C.L., Bellodi L., Benarroch F., Bienvenu O.J., Black D.W., Bloch M.H., Bruun R.D., Budman C.L., Camarena B., Cath D.C., Cavallini M.C., Chouinard S., Coric V., Cullen B., Delorme R., Denys D., Derks E.M., Dion Y., Rosário M.C., Eapen V., Evans P., Falkai P., Fernandez T.V., Garrido H., Geller D., Grabe H.J., Grados M.A., Greenberg B.D., Gross-Tsur V., Gruenblatt, E, Heiman G.A., Hemmings, SMJ, Herrera L.D., Hounie A.G., Jankovic J., Kennedy J.L., King R.A., Kurlan R., Lanzagorta N., Leboyer M., Leckman J.F., Lennertz L., Lochner C., Lowe T.L., Lyon G.J., MacCiardi F., Maier W., McCracken J.T., McMahon W., Murphy D.L., Naarden A.L., Neale B.M., Nurmi E., Pakstis A.J., Pato M.T., Pato C.N., Piacentini J., Pittenger C., Pollak Y., Reus V.I., Richter M.A., Riddle M., Robertson M.M., Rosenberg D., Rouleau G.A., Ruhrmann S., Sampaio A.S., Samuels J., Sandor P., Sheppard B., Singer H.S., Smit J.H., Stein D.J., Tischrield, JA, Vallada H., Veenstra-Vanderweele J., Walitza S., Wang Y., Wendfand, JR, Shugart Y.Y., Miguel E.C., Nicolini H., Oostra B.A., Moessner R., Wagner M., Ruiz-Linares A., Heutink P., Nestadt G., Freimer N., Petryshen T., Posthuma D., Jenike M.A., Cox N.J., Hanna G.L., Brentani H., Scherer S.W., Arnold P.D., Stewart S.E., Mathews C.A., Knowles J.A., Cook E.H., Pauls D.L., Wang K., Scharf J.M.

Publicada: 1 ago 2014
Resumen:
Objective: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method: The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results: Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to pu

Filiaciones:
McGrath L.M.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

 American University, Washington, DC, United States

 Harvard-MIT Broad Institute, Boston, United States

Yu D.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

 Harvard-MIT Broad Institute, Boston, United States

Marshall C.:
 University of Toronto, Hospital for Sick Children, Toronto, Canada

Davis L.K.:
 University of Chicago, United States

Thiruvahindrapuram B.:
 University of Toronto, Hospital for Sick Children, Toronto, Canada

Li B.:
 University of Toronto, Hospital for Sick Children, Toronto, Canada

Cappi C.:
 University of São Paulo Medical School, United States

Gerber G.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Wolf A.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Schroeder F.A.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Osiecki L.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

O'Dushlaine C.:
 Harvard-MIT Broad Institute, Boston, United States

Kirby A.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Illmann C.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Haddad S.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Gallagher P.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Fagerness J.A.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Barr C.L.:
 University of Toronto, Hospital for Sick Children, Toronto, Canada

 Toronto Western Research Institute, University Health Network, Toronto, Canada

Bellodi L.:
 Università Vita-Salute San Raffaele, Milan, Italy

Benarroch F.:
 Hadassah-Hebrew University Medical Center, Jerusalem, Israel

Bienvenu O.J.:
 Johns Hopkins University School of Medicine, Baltimore, United States

Black D.W.:
 University of Iowa College of Medicine, Iowa City, United States

Bloch M.H.:
 Yale University School of Medicine, New Haven, CT, United States

Bruun R.D.:
 North Shore-Long Island Jewish Medical Center, New Hyde Park, NY, United States

 New York University Medical Center, New York, NY, United States

Budman C.L.:
 North Shore-Long Island Jewish Medical Center, New Hyde Park, NY, United States

 Hofstra University School of Medicine, Hempstead, NY, United States

Camarena B.:
 Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico

Cath D.C.:
 Utrecht University, VU Medical Center, Amsterdam, Netherlands

 VU Medical Center, Amsterdam, Netherlands

Cavallini M.C.:
 Ospedale San Raffaele, Milan, Italy

Chouinard S.:
 University of Montreal, Canada

Coric V.:
 Yale University School of Medicine, New Haven, CT, United States

Cullen B.:
 Johns Hopkins University School of Medicine, Baltimore, United States

Delorme R.:
 Robert Debre University Hospital, Paris, French National Science Foundation, Creteil, France

 Institut Pasteur, Paris, France

Denys D.:
 Netherlands Institute for Neuroscience, Amsterdam, Netherlands

 Academic Medical Center, Amsterdam, Netherlands

Derks E.M.:
 Academic Medical Center, Amsterdam, Netherlands

Dion Y.:
 University of Montreal, Canada

Rosário M.C.:
 Federal University of São Paulo, Netherlands

Eapen V.:
 University of New South Wales, Australia

Evans P.:
 University of Chicago, United States

Falkai P.:
 University of Munich, Germany

Fernandez T.V.:
 Yale University School of Medicine, New Haven, CT, United States

Garrido H.:
 Hospital Nacional de Niños, San Jose, Costa Rica

 Clinica Herrera Amighetti, Avenida Escazú, San José, Costa Rica

Geller D.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Grabe H.J.:
 University Medicine Greifswald, Greifswald, Germany

Grados M.A.:
 Johns Hopkins University School of Medicine, Baltimore, United States

Greenberg B.D.:
 Brown Medical School, Providence, RI, United States

Gross-Tsur V.:
 Shaare Zedek Medical Center, Jerusalem, Israel

Heiman G.A.:
 Rutgers University, Piscataway Township, NJ, United States

Herrera L.D.:
 Hospital Nacional de Niños, San Jose, Costa Rica

Hounie A.G.:
 Federal University of São Paulo, Netherlands

Jankovic J.:
 Baylor College of Medicine, Houston, United States

Kennedy J.L.:
 Centre for Addiction and Mental Health, Toronto, Canada

King R.A.:
 Yale University School of Medicine, New Haven, CT, United States

Kurlan R.:
 Atlantic Neuroscience Institute, Summit, NJ, United States

Lanzagorta N.:
 Carracci Medical Group, Mexico City, Mexico

Leboyer M.:
 Robert Debre University Hospital, Paris, French National Science Foundation, Creteil, France

 Institut Mondor de Recherche Biomédicale, Créteil, France

Leckman J.F.:
 Yale University School of Medicine, New Haven, CT, United States

Lennertz L.:
 University of Bonn, Germany

Lochner C.:
 University of Stellenbosch, South Africa

Lowe T.L.:
 University of California at San Francisco, School of Medicine, United States

Lyon G.J.:
 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States

MacCiardi F.:
 University of California, Irvine, United States

Maier W.:
 University of Bonn, Germany

McCracken J.T.:
 University of California Los Angeles (UCLA), School of Medicine, United States

McMahon W.:
 University of Utah, Salt Lake City, United States

Murphy D.L.:
 National Institute of Mental Health (NIMH), Intramural Research Program, Bethesda, MD, United States

Naarden A.L.:
 Medical City Dallas Hospital, United States

Neale B.M.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

 Harvard-MIT Broad Institute, Boston, United States

Nurmi E.:
 University of California Los Angeles (UCLA), School of Medicine, United States

Pakstis A.J.:
 Yale University School of Medicine, New Haven, CT, United States

Pato M.T.:
 Zilkha Neurogenetic Institute, Los Angeles, United States

Pato C.N.:
 Zilkha Neurogenetic Institute, Los Angeles, United States

Piacentini J.:
 University of California Los Angeles (UCLA), School of Medicine, United States

Pittenger C.:
 Yale University School of Medicine, New Haven, CT, United States

Pollak Y.:
 Shaare Zedek Medical Center, Jerusalem, Israel

Reus V.I.:
 University of California at San Francisco, School of Medicine, United States

Richter M.A.:
 University of Toronto, Hospital for Sick Children, Toronto, Canada

 Sunnybrook Health Sciences Centre, Toronto, Canada

Riddle M.:
 Johns Hopkins University School of Medicine, Baltimore, United States

Robertson M.M.:
 University College London, United Kingdom

Rosenberg D.:
 Wayne State University, Detroit Medical Center, Detroit, United States

Rouleau G.A.:
 Montreal Neurological Institute, United States

Ruhrmann S.:
 University of Cologne, Germany

Sampaio A.S.:
 Federal University of São Paulo, Netherlands

 Universidade Federal da Bahia, Salvador Bahia, Brazil

Samuels J.:
 Johns Hopkins University School of Medicine, Baltimore, United States

Sandor P.:
 University of Toronto, Hospital for Sick Children, Toronto, Canada

 Toronto Western Research Institute, University Health Network, Toronto, Canada

Sheppard B.:
 University of California at San Francisco, School of Medicine, United States

Singer H.S.:
 Johns Hopkins University School of Medicine, Baltimore, United States

Smit J.H.:
 VU University Amsterdam, Netherlands

 VU Medical Center, Amsterdam, Netherlands

 VU Amsterdam and Erasmus University Medical Centre, Rotterdam, Netherlands

Stein D.J.:
 University of Cape Town, South Africa

Vallada H.:
 University of São Paulo Medical School, United States

Veenstra-Vanderweele J.:
 Vanderbilt University, Nashville, TN, United States

Walitza S.:
 University of Zurich, Switzerland

 University of Würzburg, Israel

Wang Y.:
 Johns Hopkins University School of Medicine, Baltimore, United States

Shugart Y.Y.:
 National Institute of Mental Health (NIMH), Intramural Research Program, Bethesda, MD, United States

Miguel E.C.:
 University of São Paulo Medical School, United States

Nicolini H.:
 Carracci Medical Group, Mexico City, Mexico

Oostra B.A.:
 Erasmus Medical Center Rotterdam, Netherlands

Moessner R.:
 University of Bonn, Germany

Wagner M.:
 University of Bonn, Germany

Ruiz-Linares A.:
 University College London, United Kingdom

Heutink P.:
 VU Medical Center, Amsterdam, Netherlands

 German Center for Neurodegenerative Diseases, Bonn and VU Medical Center, Amsterdam, Netherlands

Nestadt G.:
 Johns Hopkins University School of Medicine, Baltimore, United States

Freimer N.:
 University of California Los Angeles (UCLA), School of Medicine, United States

 Semel Institute for Neuroscience and Human Behavior, UCLA, United Kingdom

Petryshen T.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

 Harvard-MIT Broad Institute, Boston, United States

Posthuma D.:
 VU Amsterdam and Erasmus University Medical Centre, Rotterdam, Netherlands

Jenike M.A.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Cox N.J.:
 University of Chicago, United States

Hanna G.L.:
 University of Michigan, Ann Arbor, MI, United States

Brentani H.:
 University of São Paulo Medical School, United States

Scherer S.W.:
 University of Toronto, Hospital for Sick Children, Toronto, Canada

Arnold P.D.:
 University of Toronto, Hospital for Sick Children, Toronto, Canada

Stewart S.E.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

 University of British Columbia, Vancouver, Canada

Mathews C.A.:
 University of California at San Francisco, School of Medicine, United States

Knowles J.A.:
 Zilkha Neurogenetic Institute, Los Angeles, United States

Cook E.H.:
 University of Illinois at Chicago, United States

Pauls D.L.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

Wang K.:
 Zilkha Neurogenetic Institute, Los Angeles, United States

Scharf J.M.:
 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States

 Brigham and Womens Hospital, Boston, United States

 Harvard-MIT Broad Institute, Boston, United States
ISSN: 08908567
Editorial
LIPPINCOTT WILLIAMS & WILKINS, 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA, Países Bajos
Tipo de documento: Article
Volumen: 53 Número: 8
Páginas: 910-919
WOS Id: 000339932900011
ID de PubMed: 25062598
imagen

MÉTRICAS