Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.
Journal: Journal of the American Academy of Child and Adolescent Psychiatry
Volume: 53
Issue: 8
Year of Publication: 2015
Affiliated Institutions:
Massachusetts General Hospital, Boston; American University, Washington, DC; Harvard-MIT Broad Institute, Boston.
Massachusetts General Hospital, Boston; Harvard-MIT Broad Institute, Boston.
University of Toronto and the Hospital for Sick Children, Toronto.
University of Chicago.
University of São Paulo Medical School.
Massachusetts General Hospital, Boston.
Harvard-MIT Broad Institute, Boston.
University of Toronto and the Hospital for Sick Children, Toronto; Toronto Western Research Institute, University Health Network, Toronto.
Università Vita-Salute San Raffaele, Milan.
Hadassah-Hebrew University Medical Center, Jerusalem.
Johns Hopkins University School of Medicine, Baltimore.
University of Iowa College of Medicine, Iowa City.
Yale University School of Medicine, New Haven, CT.
North Shore-Long Island Jewish Medical Center, New Hyde Park, NY; New York University Medical Center, New York.
North Shore-Long Island Jewish Medical Center, New Hyde Park, NY; Hofstra University School of Medicine, Hempstead, NY.
Instituto Nacional de Psiquiatría Ramon de la Fuente Muñiz, Mexico.
Utrecht University and VU Medical Center, Amsterdam.
Ospedale San Raffaele, Milan.
University of Montreal.
Robert Debre University Hospital, Paris and the French National Science Foundation, Creteil, France; Institut Pasteur, Paris.
Netherlands Institute for Neuroscience, Amsterdam; Academic Medical Center, Amsterdam.
Academic Medical Center, Amsterdam.
Federal University of São Paulo.
University of New South Wales, Australia.
University of Munich.
Hospital Nacional de Niños, San Jose, Costa Rica; Clinica Herrera Amighetti, Avenida Escazú, San José, Costa Rica.
University Medicine Greifswald, Greifswald, Germany.
Brown Medical School, Providence, RI.
Shaare Zedek Medical Center, Jerusalem.
University of Zurich.
Rutgers University, Piscataway Township, NJ.
University of Stellenbosch, South Africa.
Hospital Nacional de Niños, San Jose, Costa Rica.
Baylor College of Medicine, Houston.
Centre for Addiction and Mental Health, Toronto.
Atlantic Neuroscience Institute, Summit, NJ.
Carracci Medical Group, Mexico City.
Robert Debre University Hospital, Paris and the French National Science Foundation, Creteil, France; Institut Mondor de Recherche Biomédicale, Créteil, France.
University of Bonn, Germany.
University of California at San Francisco School of Medicine.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
University of California, Irvine.
University of California, Los Angeles (UCLA) School of Medicine.
University of Utah, Salt Lake City.
National Institute of Mental Health (NIMH) Intramural Research Program, Bethesda, MD.
Medical City Dallas Hospital.
Zilkha Neurogenetic Institute, Los Angeles.
University of Toronto and the Hospital for Sick Children, Toronto; Sunnybrook Health Sciences Centre, Toronto.
University College London.
Wayne State University and Detroit Medical Center, Detroit.
Montreal Neurological Institute.
University of Cologne, Germany.
Federal University of São Paulo; Universidade Federal da Bahia, Salvador, Bahia, Brazil.
VU Amsterdam and Erasmus University Medical Centre, Rotterdam; VU University Amsterdam; VU Medical Center, Amsterdam.
University of Cape Town, South Africa.
Vanderbilt University, Nashville, TN.
University of Zurich; University of Würzburg.
Erasmus Medical Center Rotterdam, the Netherlands.
German Center for Neurodegenerative Diseases, Bonn and VU Medical Center Amsterdam.
University of California, Los Angeles (UCLA) School of Medicine; Semel Institute for Neuroscience and Human Behavior, UCLA.
VU Amsterdam and Erasmus University Medical Centre, Rotterdam.
University of Michigan, Ann Arbor, MI.
Massachusetts General Hospital, Boston; University of British Columbia, Vancouver.
University of Illinois at Chicago.
Massachusetts General Hospital, Boston; Brigham and Womens Hospital, Boston; Harvard-MIT Broad Institute, Boston. Electronic address: jscharf@partners.org.
Abstract summary
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.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.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 published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%).Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.
Authors & Co-authors:
McGrath Lauren M LM
Yu Dongmei D
Marshall Christian C
Davis Lea K LK
Thiruvahindrapuram Bhooma B
Li Bingbin B
Cappi Carolina C
Gerber Gloria G
Wolf Aaron A
Schroeder Frederick A FA
Osiecki Lisa L
O'Dushlaine Colm C
Kirby Andrew A
Illmann Cornelia C
Haddad Stephen S
Gallagher Patience P
Fagerness Jesen A JA
Barr Cathy L CL
Bellodi Laura L
Benarroch Fortu F
Bienvenu O Joseph OJ
Black Donald W DW
Bloch Michael H MH
Bruun Ruth D RD
Budman Cathy L CL
Camarena Beatriz B
Cath Danielle C DC
Cavallini Maria C MC
Chouinard Sylvain S
Coric Vladimir V
Cullen Bernadette B
Delorme Richard R
Denys Damiaan D
Derks Eske M EM
Dion Yves Y
Rosário Maria C MC
Eapen Valsama V
Evans Patrick P
Falkai Peter P
Fernandez Thomas V TV
Garrido Helena H
Geller Daniel D
Grabe Hans J HJ
Grados Marco A MA
Greenberg Benjamin D BD
Gross-Tsur Varda V
Grünblatt Edna E
Heiman Gary A GA
Hemmings Sian M J SM
Herrera Luis D LD
Hounie Ana G AG
Jankovic Joseph J
Kennedy James L JL
King Robert A RA
Kurlan Roger R
Lanzagorta Nuria N
Leboyer Marion M
Leckman James F JF
Lennertz Leonhard L
Lochner Christine C
Lowe Thomas L TL
Lyon Gholson J GJ
Macciardi Fabio F
Maier Wolfgang W
McCracken James T JT
McMahon William W
Murphy Dennis L DL
Naarden Allan L AL
Neale Benjamin M BM
Nurmi Erika E
Pakstis Andrew J AJ
Pato Michele T MT
Pato Carlos N CN
Piacentini John J
Pittenger Christopher C
Pollak Yehuda Y
Reus Victor I VI
Richter Margaret A MA
Riddle Mark M
Robertson Mary M MM
Rosenberg David D
Rouleau Guy A GA
Ruhrmann Stephan S
Sampaio Aline S AS
Samuels Jack J
Sandor Paul P
Sheppard Brooke B
Singer Harvey S HS
Smit Jan H JH
Stein Dan J DJ
Tischfield Jay A JA
Vallada Homero H
Veenstra-VanderWeele Jeremy J
Walitza Susanne S
Wang Ying Y
Wendland Jens R JR
Shugart Yin Yao YY
Miguel Euripedes C EC
Nicolini Humberto H
Oostra Ben A BA
Moessner Rainald R
Wagner Michael M
Ruiz-Linares Andres A
Heutink Peter P
Nestadt Gerald G
Freimer Nelson N
Petryshen Tracey T
Posthuma Danielle D
Jenike Michael A MA
Cox Nancy J NJ
Hanna Gregory L GL
Brentani Helena H
Scherer Stephen W SW
Arnold Paul D PD
Stewart S Evelyn SE
Mathews Carol A CA
Knowles James A JA
Cook Edwin H EH
Pauls David L DL
Wang Kai K
Scharf Jeremiah M JM
Study Outcome
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