Year: 2025
Type: review
Study design: Observational Study
Abstract: Obsessive-compulsive disorder (OCD) affects ∼1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3, CTNND1 and multiple genes in the MHC region. We estimated that ∼11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and cortex, along with D1- and D2-type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all of the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa, and Tourette syndrome, and was negatively associated with inflammatory bowel diseases, educational attainment, and body mass index.
Source: Nature Genetics
Authors: Nora I. Strom, Zachary F. Gerring, Marco Galimberti, Dongmei Yu, Matthew W. Halvorsen, Abdel Abdellaoui, Cristina Rodriguez-Fontenla, Julia M. Sealock, Tim Bigdeli, Jonathan R. Coleman, Behrang Mahjani, Jackson G. Thorp, Katharina Bey, Christie L. Burton, Jurjen J. Luykx, Gwyneth Zai, Silvia Alemany, Christine Andre, Kathleen D. Askland, Julia Bäckman, Nerisa Banaj, Cristina Barlassina, Judith Becker Nissen, O. Joseph Bienvenu, Donald Black, Michael H. Bloch, Sigrid Børte, Rosa Bosch, Michael Breen, Brian P. Brennan, Helena Brentani, Joseph D. Buxbaum, Jonas Bybjerg-Grauholm, Enda M. Byrne, Judit Cabana-Dominguez, Beatriz Camarena, Adrian Camarena, Carolina Cappi, Angel Carracedo, Miguel Casas, Maria Cristina Cavallini, Valentina Ciullo, Edwin H. Cook, Jesse Crosby, Bernadette A. Cullen, Elles J. De Schipper, Richard Delorme, Srdjan Djurovic, Jason A. Elias, Xavier Estivill, Martha J. Falkenstein, Bengt T. Fundin, Lauryn Garner, Christina Gironda, Fernando S. Goes, Marco A. Grados, Jakob Grove, Wei Guo, Jan Haavik, Kristen Hagen, Kelly Harrington, Alexandra Havdahl, Kira D. Höffler, Ana G. Hounie, Donald Hucks, Christina Hultman, Magdalena Janecka, Eric Jenike, Elinor K. Karlsson, Kara Kelley, Julia Klawohn, Janice E. Krasnow, Kristi Krebs, Christoph Lange, Nuria Lanzagorta, Daniel Levey, Kerstin Lindblad-Toh, Fabio Macciardi, Brion Maher, Brittany Mathes, Evonne McArthur, Nathaniel McGregor, Nicole C. McLaughlin, Sandra Meier, Euripedes C. Miguel, Maureen Mulhern, Paul S. Nestadt, Erika L. Nurmi, Kevin S. O’Connell, Lisa Osiecki, Olga Therese Ousdal, Teemu Palviainen, Nancy L. Pedersen, Fabrizio Piras, Federica Piras, Sriramya Potluri, Raquel Rabionet, Alfredo Ramirez, Scott Rauch, Abraham Reichenberg, Mark A. Riddle, Stephan Ripke, Maria C. Rosário, Aline S. Sampaio, Miriam A. Schiele, Anne Heidi Skogholt, Laura G. Sloofman, Jan Smit, María Soler Artigas, Laurent F. Thomas, Eric Tifft, Homero Vallada, Nathanial van Kirk, Jeremy Veenstra-VanderWeele, Nienke N. Vulink, Christopher P. Walker, Ying Wang, Jens R. Wendland, Bendik S. Winsvold, Yin Yao, Hang Zhou, Estonian Biobank, Andres Metspalu, Tõnu Esko, Reedik Mägi, Mari Nelis, Georgi Hudjashov, Chris German, Arpana Agrawal, Pino Alonso, Götz Berberich, Kathleen K. Bucholz, Cynthia M. Bulik, Danielle Cath, Damiaan Denys, Valsamma Eapen, Howard Edenberg, Peter Falkai, Thomas V. Fernandez, Abby J. Fyer, J. M. Gaziano, Dan A. Geller, Hans J. Grabe, Benjamin D. Greenberg, Gregory L. Hanna, Ian B. Hickie, David M. Hougaard, Norbert Kathmann, James Kennedy, Dongbing Lai, Mikael Landén, Stéphanie Le Hellard, Marion Leboyer, Christine Lochner, James T. McCracken, Sarah E. Medland, Preben B. Mortensen, Benjamin M. Neale, Humberto Nicolini, Merete Nordentoft, Michele Pato, Carlos Pato, David L. Pauls, John Piacentini, Christopher Pittenger, Danielle Posthuma, Josep Antoni Ramos-Quiroga, Steven A. Rasmussen, Margaret A. Richter, David R. Rosenberg, Stephan Ruhrmann, Jack F. Samuels, Sven Sandin, Paul Sandor, Gianfranco Spalletta, Dan J. Stein, S. Evelyn Stewart, Eric A. Storch, Barbara E. Stranger, Maurizio Turiel, Thomas Werge, Ole A. Andreassen, Anders D. Børglum, Susanne Walitza, Kristian Hveem, Bjarne K. Hansen, Christian Rück, Nicholas G. Martin, Lili Milani, Ole Mors, Ted Reichborn-Kjennerud, Marta Ribasés, Gerd Kvale, David Mataix-Cols, Katharina Domschke, Edna Grünblatt, Michael Wagner, John-Anker Zwart, Gerome Breen, Gerald Nestadt, Jaakko Kaprio, Paul D. Arnold, Dorothy E. Grice, James A. Knowles, Helga Ask, Karin J. Verweij, Lea K. Davis, Dirk J. Smit, James J. Crowley, Jeremiah M. Scharf, Murray B. Stein, Joel Gelernter, Carol A. Mathews, Eske M. Derks, Manuel Mattheisen
Institutions: University of Bern, Aarhus University, Region Stockholm, Karolinska Institutet, Humboldt-Universität zu Berlin, Stockholm Health Care Services, Institut für Psychiatrische Phänomik und Genomik, Ludwig-Maximilians-Universität München, Walter and Eliza Hall Institute of Medical Research, QIMR Berghofer Medical Research Institute, Yale University, VA Connecticut Healthcare System, Broad Institute, Massachusetts General Hospital, Stanley Center for Psychiatric Research, University of North Carolina at Chapel Hill, Amsterdam University Medical Centers, University of Amsterdam, Universidade de Santiago de Compostela, Center for Research in Molecular Medicine and Chronic Diseases, Instituto de Investigación Sanitaria de Santiago, Vanderbilt University, SUNY Downstate Health Sciences University, VA NY Harbor Healthcare System, King's College London, South London and Maudsley NHS Foundation Trust, National Institute for Health and Care Research, NIHR Maudsley Biomedical Research Centre, Icahn School of Medicine at Mount Sinai, The University of Queensland, University Hospital Bonn, Hospital for Sick Children, University Medical Center Utrecht, GGNet, Centre for Addiction and Mental Health, University of Toronto, Campbell Family Mental Health Research Institute, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, McLean Hospital, McMaster University, Fondazione Santa Lucia, University of Milan, Aarhus University Hospital, Johns Hopkins University, Johns Hopkins Medicine, University of Iowa, Oslo University Hospital, Norwegian University of Science and Technology, Hospital Sant Joan de Déu Barcelona, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red, Harvard University, Universidade de São Paulo, Statens Serum Institut, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Duke University, Mount Sinai Hospital, Centre for Biomedical Network Research on Rare Diseases, IRCCS Ospedale San Raffaele, University of Illinois Chicago, Assistance Publique – Hôpitaux de Paris, University of Bergen, Quantitative Genomics Medicine Laboratories (qGenomics), Lundbeck Foundation, National Institute of Mental Health, Haukeland University Hospital, Molde Hospital, Boston University, VA Boston Healthcare System, Norwegian Institute of Public Health, Lovisenberg Diakonale Sykehus, Vanderbilt University Medical Center, New York University, University of Massachusetts Chan Medical School, MSB Medical School Berlin, University of Tartu, Brigham and Women's Hospital, United States Department of Veterans Affairs, Uppsala University, Science for Life Laboratory, University of California, Irvine, Butler Hospital, Brown University, Dalhousie University, University of California, Los Angeles, University of Oslo, University of Helsinki, Institute for Molecular Medicine Finland, Institut de Recerca Sant Joan de Déu, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, The University of Texas at San Antonio Health Science Center, University of Cologne, German Center for Neurodegenerative Diseases, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University Hospital Cologne, Deutsches Zentrum für Psychische Gesundheit, Charité – Universitätsmedizin Berlin, Universidade Federal de São Paulo, Universidade Federal da Bahia, University of Freiburg, University Medical Center Freiburg, St Olav's University Hospital, New York State Psychiatric Institute, Columbia University, Rutgers, The State University of New Jersey, National Institutes of Health, Fudan University, Washington University in St. Louis, Bellvitge University Hospital, Institut d'Investigació Biomédica de Bellvitge, University Medical Center Groningen, University of Groningen, Royal Netherlands Academy of Arts and Sciences, 23andMe (United States), UNSW Sydney, Ingham Institute, South Western Sydney Local Health District, Indiana University School of Medicine, LMU Klinikum, Max Planck Institute of Psychiatry, Columbia University Irving Medical Center, Mass General Brigham, Universitätsmedizin Greifswald, Providence VA Medical Center, University of Michigan, The University of Sydney, Indiana University Indianapolis, University of Gothenburg, Inserm, Université Paris-Est Créteil, Stellenbosch University, National Institute of Genomic Medicine, University of Copenhagen, Mental Health Services, Capital Region of Denmark, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC Location Vrije Universiteit Amsterdam, Sunnybrook Health Science Centre, Wayne State University, Baylor College of Medicine, South African Medical Research Council, University of Cape Town, University of British Columbia, BC Mental Health & Substance Use Services, BC Children's Hospital Research Institute, Northwestern University, Copenhagen University Hospital, University of Zurich, ETH Zurich, Psychiatrische Universitätsklinik Zürich, Senter for Krisepsykologi, University of Calgary, Mathison Centre for Mental Health Research and Education, Amsterdam UMC Location University of Amsterdam, University of California San Diego, VA San Diego Healthcare System, University of Florida
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: U.S. Department of Veterans Affairs, Massachusetts General Hospital, Klarman Family Foundation, Yale University, Office of Research and Development, Brown University, Vanderbilt University, McLean Hospital, Wayne State University, International OCD Foundation, Northwestern University, State University of New York, Aarhus Universitet, Aarhus Universitetshospital, Helsingin Yliopisto, Johns Hopkins University, Fundació la Marató de TV3, Norges Teknisk-Naturvitenskapelige Universitet, South London and Maudsley NHS Foundation Trust, McMaster University, Queensland Health, BC Children's Hospital, Università degli Studi di Milano, Beatrice and Samuel A. Seaver Foundation, Vanderbilt University Medical Center, QIMR Berghofer Medical Research Institute, Broad Institute, Ministerio de Ciencia, Innovación y Universidades, Trond Mohn stiftelse, Georgia Clinical and Translational Science Alliance, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela, Della Martin Foundation, Stichting Volksbond Rotterdam, Amsterdam University Medical Centers, Ontario Council on Graduate Studies, Council of Ontario Universities, National Institute for Health and Care Research, Department of Health and Social Care, King's College London, European Commission, National Research Foundation, South African Medical Research Council, Deutsche Forschungsgemeinschaft, Institut National de la Santé et de la Recherche Médicale, Rijksuniversiteit Groningen, Koninklijke Nederlandse Akademie van Wetenschappen, University of New South Wales, University of Queensland, Universiteit van Amsterdam, Vrije Universiteit Amsterdam, Bundesministerium für Bildung und Forschung, AFA Försäkring, Gentofte Hospital, Eidgenössische Technische Hochschule Zürich, Ministero della Salute, Fudan University, Ministero dell’Istruzione, dell’Università e della Ricerca, Helse- og Omsorgsdepartementet, Lundbeckfonden, University of Toronto, Karolinska Institutet, Novo Nordisk, Stockholms Läns Landsting, Vetenskapsrådet, Universiteit Stellenbosch, Helse Midt-Norge, Universitetet i Bergen, Universitair Medisch Centrum Groningen, Deutsches Zentrum für Neurodegenerative Erkrankungen, Region Hovedstaden, Universitetet i Oslo, Norges Forskningsråd, Göteborgs Universitet, Universitat de Barcelona, Hospital for Sick Children, Humboldt-Universität zu Berlin, Universität Zürich, Forskningsrådet om Hälsa, Arbetsliv och Välfärd, Centro de Investigación Biomédica en Red de Salud Mental, University of Cape Town, Tartu Ülikool, European College of Neuropsychopharmacology, Universität zu Köln, Universitätsspital Zürich, Université Paris-Est Créteil Val-de-Marne, Novo Nordisk Fonden, Assistance publique-Hôpitaux de Paris, Universitat Autònoma de Barcelona, St. Olavs Hospital Universitetssykehuset i Trondheim, Fundació Institut de Recerca Hospital Universitari Vall d’Hebron, H. Lundbeck A/S, Ingham Institute for Applied Medical Research, Instituto Nacional de Medicina Genómica, Universidade de Santiago de Compostela, Amsterdam Neuroscience, National Institutes of Health, University of North Carolina at Chapel Hill, Feinberg School of Medicine, SUNY Downstate Medical Center, School of Medicine, Indiana University, Campbell Family Mental Health Research Institute, Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Stanley Center for Psychiatric Research, Broad Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, Department of Psychiatry, Columbia University, Department of Psychiatry, University of Toronto, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Cereal Partners Worldwide, Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, NIHR Maudsley Biomedical Research Centre, National Center for PTSD, U.S. Department of Veterans Affairs, Fakultet for medisin og helsevitenskap, Norges Teknisk-Naturvitenskapelige Universitet, Department of Psychiatry, Faculty of Medicine, University of British Columbia, Medical Research Council, National Health and Medical Research Council, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, European Regional Development Fund, Neuroscience Center Zurich, University of Zurich, Center for Innovative Medicine, Faculty of Medicine and Health, University of Sydney, Norwegian Institute of Public Health, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, NIH Clinical Center, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, European Social Fund, FP7 Health
Awards: G1022082625, G103528551, G1085576015, Behavioral Genetics and Neuropsychiatric Disorders in a Natural Model System, G1182793083, G1188586094, Collaborative OCD Genetics Study, G1274085498, G1297207816, Advancing drug repositioning and development for Alzheimer's Disease using functional genomics and computational phenomics, G1390942713, G1435936284, Pharmacogenomics of Arrhythmia Therapy, G1482489452, G1490400109, G1531600799, LINKAGE &ASSOCIATION IN OBSESSIVE-COMPULSIVE DISORDER, Integrating Common and Rare Variation to Discover Genes Associated with Tourette Syndrome, G1766209448, G1795826554, G1846282300, OCD Collaborative Genetics Association Study, G1922020140, G1951620746, G2043477120, G2048194553, G2076520454, G2103760183, G214445032, G2209161966, Understanding the genetic risk underlying racial disparities in uterine fibroids, G2242242560, G2308744219, PREADAPT - Identifizierung personalisierter Entzündungsprofile des Alterns und ihre Auswirkungen auf die Demenzentwicklung - Teilprojekt: Definition eines altersbedingten SASP-Scores, welcher den kognitiven Abbau moduliert und Identifizierung der zugrundeliegenden genetischen Faktoren, G2323639618, G2325242462, Action Monitoring and Genomic Variants in Pediatric Obsessive-Compulsive Behavior, G2615776415, G2683268942, G2719215791, G2759730755, G2924140200, Neurogenetic Investigations of Obsessive-Compulsive Disorder, G2956829171, OCD: Novel Comparative Genomic Approaches to Identify Disease and Treatment Mechanisms, G3045084321, G3061433778, Investigating the Genomic Architecture of Anxiety and Overlap with Mental Health Disorders in the Million Veteran Program., Más allá del riesgo genético para el TDAH: contribución genética a la resiliencia en una muestra clínica, Biomarcadores multi-ómicos periféricos predictores de la evolución a largo plazo del Trastorno Obsesivo-Compulsivo: la cohorte TOC Barcelona (OCD-BC), G3246699782, G3277956970, G3281292808, G3298186876, G332351177, Genetics of Alcohol Dependence in African Americans: Recruitment, Improving Prediction of Drug Action, G3376032223, G3377182240, G3395468139, G3433676821, MOLECULAR GENETICS OF OBSESSIVE COMPULSIVE DISORDER, Obsessive-Compulsive Disorder: Novel comparative genomic approaches to identification of disease and treatment mechanisms, Mental health and chronic disease: A psycheMERGE investigation into the shared biology underlying psychiatric disorders and their physical comorbidities, G3619590958, G3623979720, G363525713, G364208108, Advancing our understanding of Psychiatric Disorders through Imaging and Genetics, G3771220633, G3784421331, G3791753988, G3809296745, Risk and Resilience in Developmental Diversity and Mental Health, G3884610240, Using genomics to understand psychiatric disorders, G3938985443, G3987400284, Postpartum Depression: Action Towards Causes and Treatment, G4049315607, G4070137766, G4107354744, G4128221539, G4198746417, G4218682071, Automated Storage and Retrieval of Biological Systems, G4258172611, G4261582792, European Network for Genetic-Epidemiological Studies: building a method to dissect complex genetic traits, using essential hypertension as a disease model, G434337789, G4395870004, G4398881426, G4410787187, G4425699080, Multivariate whole genome estimation and prediction analysis of genomics data applied to psychiatric disorders, Understanding and treating Obsessive-Compulsive and Related Disorders: etiology, epidemiology, treatment development and outcome, Predicting health outcomes and labor market marginalization after treatment in common mental disorders using Machine Learning, G4493028280, G4538986684, G4591372979, PRiMED: Predicting Response to CBT in Mental Disorders using multimodal data and machine learning, Más allá del riesgo genético para el TDAH: contribución genética a la resiliencia en una muestra poblacional, Obsessive-compulsive disorder (OCD) Collaborative Genetics Association Study, G4750876853, UCLA-Caltech Medical Scientist Training Program, G5408826359, G5497799976, G5511928619, G5554424168, G5580019600, G560889077, G5628911745, G563474107, Tackling heterogeneity in the etiology of major depressive disorder, Addition of OCD to the Genomic Psychiatry Cohort, G5679716143, G5717004637, G57820259, G5821054634, G5834621717, G5868276417, G5926161409, FAMILY STUDY OF OBSESSIVE-COMPULSIVE DISORDER, Genetic Epidemiology of Multiple Sclerosis, User-friendly ICT tools to enhance self-management and effective treatment of depression in the EU, G6058185027, G6173849340, G6263508347, G6305174853, G6346618796, G6368058359, OCD Collaborative Genetics Association Study, G6589054092, G659731888, Genomics of OCD in Latin American Communities, G662545860, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, Large-Scale Collaborative Genetic and Epigenetic Studies of Tourette Syndrome, 2/3 Brain Function and Genetics in Pediatric Obsessive-Compulsive Behaviors, G6742998398, G6809934652, From gene discovery to clinical drug development for neuropsychiatric disorders, G6858189587, G6877267764, VESPA: Vanderbilt Electronic Systems for Pharmacogenomic Assessment, Modelos predictivos basados en datos genéticos, transcriptómicos y de micro ARN para el estudio del TDAH: un enfoque multiómico, G6988210397, Predicting comorbid cardiovascular disease in individuals with mental disorder by decoding disease mechanisms, Training Program on Genetic Variation and Human Phenotypes, G7044663616, Estudio de asociación a escala transcriptómica (TWAS) en Trastorno por Déficit de Atención con Hiperactividad (TDAH), G712881263, G7163342664, G7303354750, G7389299803, Genetic & Environmental Predictors of Tourette Syndrome & OCD in Denmark, G7612322874, G7653134492, The Vanderbilt Institute for Clinical and Translational Research (VICTR), OCD Collaborative Genetics Association Study, Vanderbilt Genome Electronic Records Project, G79382232, Discovering Biology for Neuropsychiatric Diseases Through Omics Studies on Comorbidities, G806246556, G8098630230, G8117232887, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8332127685, Obsessive-compulsive disorder (OCD) Collaborative Genetics Association Study, G8538723892, G8878202614, 1/2-D-Cycloserine Augmentation of CBT for Pediatric OCD, G9000033427, G9000300101, 7/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact, Vanderbilt Institute for Clinical and Translational Research (VICTR), 5/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact, 1/2 Rare Genetic Variation and Risk for Obsessive Compulsive Disorder, Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS), 1/7 PGC: Advancing Discovery and Impact, Multimodal Investigation of Excitatory/Inhibitory Imbalances and Network Dysfunction Related to Motor Control in OCD Youth: ùH fMRS and fMRI Applications, 2/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact, Collaborative Study on the Genetics of Alcoholism (COGA).
OpenAlex ID: W4410325451