RT Journal Article
T1 Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia
A1 Costas Costas, Javier
A1 Carrera, Noa
A1 Alonso, Pino
A1 Gurriarán Bas, Xaquín
A1 Segalàs, Cinto
A1 Real, Eva
A1 López Solà, Clara
A1 Mas, Sebastian
A1 Gassó, Patricia
A1 Domènech Salgado, Laura
A1 Morell, Marta
A1 Quintela García, Inés
A1 Lázaro, Luisa
A1 Menchón, José M.
A1 Estivill, Xavier
A1 Carracedo Álvarez, Ángel
AB Common single-nucleotide polymorphisms (SNPs) account for a large proportion of the heritability of obsessive-compulsivedisorder (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 associatedwith OCD by SNP-based and gene-based tests; and to test the existence of a polygenic risk shared with schizophrenia. The primaryanalysis was an exon-focused genome-wide association study of 370 OCD cases and 443 controls from Spain. A polygenic riskmodel based on the Psychiatric Genetics Consortium schizophrenia data set (PGC-SCZ2) was tested in our OCD data. A polygenicrisk model based on our OCD data was tested on previous data of schizophrenia from our group. The most significant association atthe gene-based test was found atDNM3(P= 7.9 × 10−5), a gene involved in synaptic vesicle endocytosis. The polygenic risk modelfrom PGC-SCZ2 data was strongly associated with disease status in our OCD sample, reaching its most significant value afterremoval of the major histocompatibility complex region (lowestP= 2.3 × 10−6, explaining 3.7% of the variance). The sharedpolygenic risk was confirmed in our schizophrenia data. In conclusion,DNM3may be involved in risk to OCD. The shared polygenicrisk between schizophrenia and OCD may be partially responsible for the frequent comorbidity of both disorders, explainingepidemiological data on cross-disorder risk. This common etiology may have clinical implications.
PB Nature Publishing Group
SN 2045-2322
YR 2016
FD 2016
LK http://hdl.handle.net/10347/22675
UL http://hdl.handle.net/10347/22675
LA eng
NO Costas, J., Carrera, N., Alonso, P. et al. Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia. Transl Psychiatry 6, e768 (2016). https://doi.org/10.1038/tp.2016.34
NO The study was supported by Fundación María José Jove, Fondo Europeo de DesarrolloRegional (FEDER), Xunta de Galicia; and by grants from the Instituto de Salud Carlos IIIFIS PI13/01136 to AC, CP11/00163 to JC, PI13/00918 to JMM, PI14/00413 to PA; theGeneralitat de Catalunya AGAUR 2014 SGR-1138; the Spanish MINIECO SAF2013-49108-R
DS Minerva
RD 24 abr 2026