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

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...

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Main Authors:	Costas, J, Carrera, N, Alonso, P, Gurriarán, X, Segalàs, C, Real, E, López-Solà, C, Mas, S, Gassó, P, Domènech, L, Morell, M, Quintela, I, Lázaro, L, Menchón, J M, Estivill, X, Carracedo, Á
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872458/

id	pubmed-4872458
recordtype	oai_dc
spelling	pubmed-48724582016-05-27 Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia Costas, J Carrera, N Alonso, P Gurriarán, X Segalàs, C Real, E López-Solà, C Mas, S Gassó, P Domènech, L Morell, M Quintela, I Lázaro, L Menchón, J M Estivill, X Carracedo, Á Original Article 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. Nature Publishing Group 2016-03 2016-03-29 /pmc/articles/PMC4872458/ /pubmed/27023174 http://dx.doi.org/10.1038/tp.2016.34 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ 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/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Costas, J Carrera, N Alonso, P Gurriarán, X Segalàs, C Real, E López-Solà, C Mas, S Gassó, P Domènech, L Morell, M Quintela, I Lázaro, L Menchón, J M Estivill, X Carracedo, Á
spellingShingle	Costas, J Carrera, N Alonso, P Gurriarán, X Segalàs, C Real, E López-Solà, C Mas, S Gassó, P Domènech, L Morell, M Quintela, I Lázaro, L Menchón, J M Estivill, X Carracedo, Á Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia
author_facet	Costas, J Carrera, N Alonso, P Gurriarán, X Segalàs, C Real, E López-Solà, C Mas, S Gassó, P Domènech, L Morell, M Quintela, I Lázaro, L Menchón, J M Estivill, X Carracedo, Á
author_sort	Costas, J
title	Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia
title_short	Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia
title_full	Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia
title_fullStr	Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia
title_full_unstemmed	Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia
title_sort	exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia
description	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.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872458/
_version_	1613581340494528512

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

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