Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ove...

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Detalles Bibliográficos
Autores: Cormand Rifà, Bru, Psychiatric Genomics Consortium
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/126719
Acceso en línea:https://hdl.handle.net/2445/126719
Access Level:acceso abierto
Palabra clave:Psiquiatria
Genètica mèdica
Psychiatry
Medical genetics
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spelling Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathwaysCormand Rifà, BruPsychiatric Genomics ConsortiumPsiquiatriaGenètica mèdicaPsychiatryMedical geneticsGenome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.Nature Publishing Group2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/126719Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1038/nn.3922Nature Neuroscience, 2015, vol. 18, num. 2, p. 199-209https://doi.org/10.1038/nn.3922(c) Cormand Rifà, Bru, 2015info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1267192026-05-27T06:46:51Z
dc.title.none.fl_str_mv Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
title Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
spellingShingle Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
Cormand Rifà, Bru
Psiquiatria
Genètica mèdica
Psychiatry
Medical genetics
title_short Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
title_full Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
title_fullStr Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
title_full_unstemmed Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
title_sort Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
dc.creator.none.fl_str_mv Cormand Rifà, Bru
Psychiatric Genomics Consortium
author Cormand Rifà, Bru
author_facet Cormand Rifà, Bru
Psychiatric Genomics Consortium
author_role author
author2 Psychiatric Genomics Consortium
author2_role author
dc.subject.none.fl_str_mv Psiquiatria
Genètica mèdica
Psychiatry
Medical genetics
topic Psiquiatria
Genètica mèdica
Psychiatry
Medical genetics
description Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/126719
url https://hdl.handle.net/2445/126719
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1038/nn.3922
Nature Neuroscience, 2015, vol. 18, num. 2, p. 199-209
https://doi.org/10.1038/nn.3922
dc.rights.none.fl_str_mv (c) Cormand Rifà, Bru, 2015
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Cormand Rifà, Bru, 2015
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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