dc.contributor
[Strom NI] Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany. Department of Psychiatric Phenomics and Genomics (IPPG), Ludwig-Maximilians University Munich, Munich, Germany. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Services, Region Stockholm, Stockholm, Sweden. Department of Biomedicine, Aarhus University, Aarhus, Denmark. University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland. [Gerring ZF] Department of Mental Health and Neuroscience, Translational Neurogenomics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Department of Population Health and Immunity, Healthy Development and Ageing, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. [Galimberti M] Department of Psychiatry, Human Genetics, Yale University, New Haven, CT, USA. VA Connecticut Healthcare System, West Haven, CT, USA. [Yu D] Department of Center for Genomic Medicine, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. [Halvorsen MW] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. [Abdellaoui A] Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands. [Alemany S, Cabana-Dominguez S] Grup de Recerca de Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid, Spain. [Soler Artigas M, Ribasés M] Grup de Recerca de Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid, Spain. Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain. [Ramos-Quiroga JA] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. CIBERSAM, Barcelona, Spain. Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
dc.description.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 and CTNND1 and multiple genes in the major histocompatibility complex (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 the 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 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.
