title: Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia.
abstract: Common single-nucleotide polymorphisms (SNPs) account for a large proportion of the heritability of obsessive-compulsive disorder (OCD). Co-ocurrence of OCD and schizophrenia is commoner than expected based on their respective prevalences, complicating the clinical management of patients. This study addresses two main objectives: to identify particular genes associated with OCD by SNP-based and gene-based tests; and to test the existence of a polygenic risk shared with schizophrenia. The primary analysis was an exon-focused genome-wide association study of 370 OCD cases and 443 controls from Spain. A polygenic risk model based on the Psychiatric Genetics Consortium schizophrenia data set (PGC-SCZ2) was tested in our OCD data. A polygenic risk model based on our OCD data was tested on previous data of schizophrenia from our group. The most significant association at the gene-based test was found at DNM3 (P=7.9 × 10(-5)), a gene involved in synaptic vesicle endocytosis. The polygenic risk model from PGC-SCZ2 data was strongly associated with disease status in our OCD sample, reaching its most significant value after removal of the major histocompatibility complex region (lowest P=2.3 × 10(-6), explaining 3.7% of the variance). The shared polygenic risk was confirmed in our schizophrenia data. In conclusion, DNM3 may be involved in risk to OCD. The shared polygenic risk between schizophrenia and OCD may be partially responsible for the frequent comorbidity of both disorders, explaining epidemiological data on cross-disorder risk. This common etiology may have clinical implications.
authors.affiliation: Grupo de Xenética Psiquiátrica, Instituto de Investigación Sanitaria de Santiago, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde, Santiago de Compostela, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Costas
authors.affiliation: Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.|Fundación Pública Galega de Medicina Xenómica, Servicio Galego de Saúde, Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Carrera
authors.affiliation: OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona, Spain.|Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.|Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Alonso
authors.affiliation: Grupo de Xenética Psiquiátrica, Instituto de Investigación Sanitaria de Santiago, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde, Santiago de Compostela, Spain.|Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: X
authors.initials: X
authors.lastname: Gurriarán
authors.affiliation: OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona, Spain.|Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Segalàs
authors.affiliation: OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona, Spain.|Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Real
authors.affiliation: OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona, Spain.|Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: López-Solà
authors.affiliation: Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.|Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Mas
authors.affiliation: Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.|Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Gassó
authors.affiliation: Genomics and Disease Group, Centre for Genomic Regulation, Barcelona, Spain.|Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.|Centro de Investigación Biomédica en Red Epidemiología y Salud Pública, Centre for Genomic Regulation, Barcelona, Spain.|Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Domènech
authors.affiliation: Genomics and Disease Group, Centre for Genomic Regulation, Barcelona, Spain.|Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.|Centro de Investigación Biomédica en Red Epidemiología y Salud Pública, Centre for Genomic Regulation, Barcelona, Spain.|Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Morell
authors.affiliation: Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado - Instituto Carlos III, Santiago de Compostela, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras, Santiago de Compostela, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Quintela
authors.affiliation: Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.|Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.|Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.|Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Lázaro
authors.affiliation: OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona, Spain.|Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Madrid, Spain.|Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Menchón
authors.affiliation: Genomics and Disease Group, Centre for Genomic Regulation, Barcelona, Spain.|Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.|Centro de Investigación Biomédica en Red Epidemiología y Salud Pública, Centre for Genomic Regulation, Barcelona, Spain.|Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.affiliation: Fundación Pública Galega de Medicina Xenómica, Servicio Galego de Saúde, Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.|Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado - Instituto Carlos III, Santiago de Compostela, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras, Santiago de Compostela, Spain.
authors.forename: Á
authors.initials: Á
authors.lastname: Carracedo
mesh_terms: D016022:Case-Control Studies; D034286:Dynamin III / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D034286:Dynamin III