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
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