Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia.

Costas, Javier; Carrera, Noa; Alonso, Pino; Gurriarán, X.; Segalàs, Cinto; Real, Eva; López-Solà, Clara; Mas, Sebastian; Gassó, Patricia; Domènech Salgado, Laura, 1989-; Morell, Marta; Quintela Garcia, Ines; Lázaro, Luisa; Menchón, José M.; Estivill, Xavier, 1955-; Carracedo, Ángel

Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia.

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dc.contributor.author Costas, Javierca
dc.contributor.author Carrera, Noaca
dc.contributor.author Alonso, Pinoca
dc.contributor.author Gurriarán, X.ca
dc.contributor.author Segalàs, Cintoca
dc.contributor.author Real, Evaca
dc.contributor.author López-Solà, Claraca
dc.contributor.author Mas, Sebastianca
dc.contributor.author Gassó, Patriciaca
dc.contributor.author Domènech Salgado, Laura, 1989-ca
dc.contributor.author Morell, Martaca
dc.contributor.author Quintela Garcia, Inesca
dc.contributor.author Lázaro, Luisaca
dc.contributor.author Menchón, José M.ca
dc.contributor.author Estivill, Xavier, 1955-ca
dc.contributor.author Carracedo, Ángelca
dc.date.accessioned 2016-05-02T08:18:04Z
dc.date.available 2016-05-02T08:18:04Z
dc.date.issued 2016
dc.description.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.ca
dc.description.sponsorship The study was supported by Fundación María José Jove, Fondo Europeo de Desarrollo Regional (FEDER), Xunta de Galicia; and by grants from the Instituto de Salud Carlos III FIS PI13/01136 to AC, CP11/00163 to JC, PI13/00918 to JMM, PI14/00413 to PA; the Generalitat de Catalunya AGAUR 2014 SGR-1138; the Spanish MINIECO SAF2013-49108- R Plan Estatal; and the European Commission 7th Framework Program, Project N. 262055 (ESGI) to XE. LD is supported by a Severo Ochoa fellowship of the Spanish MINIECO.
dc.format.mimetype application/pdfca
dc.identifier.citation Costas J, Carrera N, Alonso P, Gurriarán X, Segalàs C, Real E et al. Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia. Transl Psychiatry. 2016 Mar 29;6:e768. DOI: 10.1038/tp.2016.34ca
dc.identifier.doi http://dx.doi.org/10.1038/tp.2016.34
dc.identifier.issn 2158-3188
dc.identifier.uri http://hdl.handle.net/10230/26228
dc.language.iso engca
dc.publisher Nature publishing groupca
dc.relation.ispartof Translational Psychiatry. 2016 Mar 29;6:e768
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/262055
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-49108-R
dc.rights This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
dc.subject.other Neurosi obsessivaca
dc.subject.other Esquizofrèniaca
dc.subject.other Gens humansca
dc.title Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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