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Title: Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia
Author: Costas, Javier
Carrera, Noa
Alonso, Pino
Gurriarán, X.
Segalàs Cosi, Cinto
Real, Eva
López Solà, Clara
Mas Herrero, Sergi
Gassó Astorga, Patricia
Domènech, Lluis
Morell, Marta
Quintela, Inés
Lázaro García, Luisa
Menchón Magriñá, José Manuel
Estivill, Xavier, 1955-
Carracedo, Arkaitz
Keywords: Neurosi obsessiva
Herència humana
Malalties hereditàries
Genètica humana
Obsessive-compulsive disorder
Heredity in humans
Genetic diseases
Human genetics
Issue Date: 29-Mar-2016
Publisher: Nature Publishing Group
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.
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It is part of: Translational Psychiatry, 2016, num. 6, p. e768
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ISSN: 2158-3188
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