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Genome-Wide Association Study of Obsessive-Compulsive Disorder Molecular Psychiatry (2013) 18, 788 -- 798 & 2013 Macmillan Publishers Limited All rights reserved 1359-4184/13 www.nature.com/mp ORIGINAL ARTICLE Genome-wide association study of obsessive-compulsive disorder SE Stewart1,2,3,70,DYu1,2,70, JM Scharf1,2,4,5,7,70, BM Neale1,6,7,70, JA Fagerness1,2,70, CA Mathews8,70, PD Arnold9,10,70, PD Evans11, ER Gamazon11, L Osiecki1,2, L McGrath1,2, S Haddad1,2, J Crane1,2, D Hezel1,2, C Illman1,2, C Mayerfeld1,2, A Konkashbaev11, C Liu12, A Pluzhnikov11, A Tikhomirov11, CK Edlund13,14, SL Rauch15, R Moessner16, P Falkai17, W Maier16, S Ruhrmann18, H-J Grabe19, L Lennertz16, M Wagner16, L Bellodi20, MC Cavallini21, MA Richter10,22, EH Cook Jr23, JL Kennedy10,24, D Rosenberg25,26, DJ Stein27, SMJ Hemmings28, C Lochner28, A Azzam8, DA Chavira29, E Fournier30, H Garrido30, B Sheppard8, P Uman˜a30, DL Murphy31, JR Wendland31,32, J Veenstra-VanderWeele33, D Denys34, R Blom34, D Deforce35, F Van Nieuwerburgh35, HGM Westenberg34, S Walitza36, K Egberts37, T Renner37, EC Miguel38, C Cappi38, AG Hounie38, M Conceic¸a˜o do Rosa´rio38, AS Sampaio38,39, H Vallada38, H Nicolini40,41, N Lanzagorta41, B Camarena42, R Delorme43,44,45, M Leboyer43,44,45, CN Pato46, MT Pato46, E Voyiaziakis46, P Heutink47, DC Cath48,49, D Posthuma47, JH Smit49, J Samuels50, OJ Bienvenu50, B Cullen50, AJ Fyer51,52, MA Grados50, BD Greenberg53, JT McCracken54, MA Riddle50, Y Wang50, V Coric55, JF Leckman56, M Bloch55, C Pittenger55, V Eapen57, DW Black58, RA Ophoff59,60, E Strengman59,60, D Cusi61,62, M Turiel63, F Frau61,64, F Macciardi65, JR Gibbs66, MR Cookson66, A Singleton66 for the North American Brain Expression Consortium, J Hardy67, for the UK Brain Expression Database, AT Crenshaw68, MA Parkin68, DB Mirel68, DV Conti13,14, S Purcell1,2,5,68,71, G Nestadt50,71, GL Hanna69,71, MA Jenike1,2,71, JA Knowles46,71, N Cox11,71 and DL Pauls1,2,71 1Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Harvard Medical School, Boston, MA, USA; 2Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; 3British Columbia Mental Health and Addictions Research Institute, University of British Columbia, Vancouver, BC, Canada; 4Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; 5Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA; 6Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; 7Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; 8Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; 9Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; 10Department of Psychiatry, University of Toronto, Toronto, ON, Canada; 11Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA; 12Department of Psychiatry, University of Chicago, Chicago, IL, USA; 13Department of Preventative Medicine, Division of Biostatistics, Keck School of Medicine, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA, USA; 14Epigenome Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 15Partners Psychiatry and McLean Hospital, Boston, MA, USA; 16Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany; 17Department of Psychiatry and Psychotherapy, University of Go¨ttingen, Go¨ ttingen, Germany; 18Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany; 19Department of Psychiatry and Psychotherapy, Helios-Hospital Stralsund, University Medicine Greifswald, Greifswald, Germany; 20Psychiatry Universita Vita-Salute San Raffaele, Milano, Italy; 21Fondazione Centro San Raffaele del Monte Tabor, Milano, Italy; 22Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 23Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA; 24Centre for Addiction and Mental Health, Toronto, ON, Canada; 25Child Psychiatry and Psychology, Wayne State University, Detroit, MI, USA; 26Children’s Hospital of Michigan, Detroit, MI, USA; 27University of Cape Town, Cape Town, South Africa; 28University of Stellenbosch, Stellenbosch, South Africa; 29Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; 30Hospital Nacional de Nin˜os, San Jose´, Costa Rica; 31Laboratory of Clinical Science, NIMH Intramural Research Program, Bethesda, MD, USA; 32CNS Clinical Biomarker Group, Pharma Research and Early Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland; 33Departments of Psychiatry, Pediatrics, and Pharmacology, Kennedy Center for Research on Human Development, and Brain Institute, Vanderbilt University, Nashville, TN, USA; 34Department of Psychiatry, Academic Medical Center and Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences (NIN-KNAW), Amsterdam, The Netherlands; 35Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium; 36Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland; 37Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wu¨rzburg, Wu¨ rzburg, Germany; 38Department of Psychiatry, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; 39University Health Care Services - SMURB, Federal University of Bahia, Salvador, Brazil; 40Centre for Genomic Sciences, University of Mexico City, Mexico City, Mexico; 41Carracci Medical Group, Mexico City, Mexico; 42Instituto Nacional de Psiquiatrı´a Ramo´n de la Fuente Mun˜iz, Depto. de Gene´tica Psiquia´trica, Mexico City, Mexico; 43AP-HP, Robert Debre´ Hospital, Department of Child and Adolescent Psychiatry, INSERM U955, Paris, France; 44Institut Mondor de Recherche Biome´dicale, Psychiatric Genetics, Cre´teil, France; 45Foundation Fondamental, French National Science Foundation, Cre´teil, France; 46Department of Psychiatry and The Behavioral Sciences, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 47Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center Amsterdam, Amsterdam, The Netherlands; 48Department of Psychiatry, VU University Medical Center and Department of Clinical and Health Psychology, Utrecht University, Utrecht, The Netherlands; 49Department of Psychiatry, EMGO Institute, VU University Medical Center, Utrecht, The Netherlands; 50Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 51Department of Psychiatry, College of Physicians and Surgeons at Columbia University, New York City, NY, USA; 52New York State Psychiatric Institute, New York City, NY, USA; 53Department of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Providence, RI, USA; 54Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, School of Medicine, Los Angeles, CA, USA; 55Child Study Centre and Department of Psychiatry, Yale University, New Haven, CT, USA; 56Child Study Centre, Pediatrics and Psychology, Yale University, New Haven, CT, USA; 57Infant, Child and Adolescent Psychiatry, University of New South Wales, Academic Unit of Child Psychiatry South West Sydney (AUCS), Sydney, NSW, Australia; 58University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA; 59UCLA Center for Neurobehavioral Genetics, Los Angeles, CA, USA; 60University Medical Center Utrecht, Utrecht, The Netherlands; 61Department of Medicine, Surgery and Dentistry, Graduate School of Nephrology, University of Milano, Milano, Italy; 62Division of Nephrology, San Paolo Hospital, Milano, Italy; 63Department of Health Technologies, University of Milano, Milano, Italy; 64Filarete Foundation, Milano, Italy; 65Department of Psychiatry and Human Behavior, School of Medicine, University of California Irvine (UCI), Irvine, CA, USA; 66Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; 67Department of Molecular Neuroscience, University College of London, Institute of Neurology, London, UK; 68The Broad Institute of Harvard-MIT, Cambridge, MA, USA; 69Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. Correspondence: Dr SE Stewart, Department of Psychiatry, University of British Columbia, A3-118, 938 West 28th Avenue, OCD Clinic, BCMHARI at CFRI, Vancouver, BC V5Z 4H4, Canada or Dr DL Pauls, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA 02114, USA. E-mail: [email protected] or [email protected] 70These authors contributed equally to this work. 71These are co-senior authors. Received 4 January 2012; revised 3 May 2012; accepted 7 May 2012; published online 14 August 2012 Genome-wide association study of OCD SE Stewart et al 789 Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched
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