An integrated analysis of genes and functional pathways for aggression in human and rodent models

Human genome-wide association studies (GWAS), transcriptome analyses of animal models, and candidate gene studies have advanced our understanding of the genetic architecture of aggressive behaviors. However, each of these methods presents unique limitations. To generate a more confident and comprehe...

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Autores: Zhang-James, Yanli, Fernàndez Castillo, Noèlia, Hess, Jonathan L., Malki, Karim, Glatt, Stephen J., Cormand Rifà, Bru, Faraone, Stephen V.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/166860
Acceso en línea:https://hdl.handle.net/2445/166860
Access Level:acceso abierto
Palabra clave:Genètica
Agressivitat
Genetics
Aggressiveness
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spelling An integrated analysis of genes and functional pathways for aggression in human and rodent modelsZhang-James, YanliFernàndez Castillo, NoèliaHess, Jonathan L.Malki, KarimGlatt, Stephen J.Cormand Rifà, BruFaraone, Stephen V.GenèticaAgressivitatGeneticsAggressivenessHuman genome-wide association studies (GWAS), transcriptome analyses of animal models, and candidate gene studies have advanced our understanding of the genetic architecture of aggressive behaviors. However, each of these methods presents unique limitations. To generate a more confident and comprehensive view of the complex genetics underlying aggression, we undertook an integrated, cross-species approach. We focused on human and rodent models to derive eight gene lists from three main categories of genetic evidence: two sets of genes identified in GWAS studies, four sets implicated by transcriptome-wide studies of rodent models, and two sets of genes with causal evidence from online Mendelian inheritance in man (OMIM) and knockout (KO) mice reports. These gene sets were evaluated for overlap and pathway enrichment to extract their similarities and differences. We identified enriched common pathways such as the G-protein coupled receptor (GPCR) signaling pathway, axon guidance, reelin signaling in neurons, and ERK/MAPK signaling. Also, individual genes were ranked based on their cumulative weights to quantify their importance as risk factors for aggressive behavior, which resulted in 40 top-ranked and highly interconnected genes. The results of our cross-species and integrated approach provide insights into the genetic etiology of aggression.Nature Publishing Group2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/166860Articles 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/s41380-018-0068-7Molecular Psychiatry, 2018, vol. 24, num. 11, p. 1655-1666https://doi.org/10.1038/s41380-018-0068-7info:eu-repo/grantAgreement/EC/H2020/667302(c) Zhang-James, Yanli et al., 2018info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1668602026-05-27T06:46:51Z
dc.title.none.fl_str_mv An integrated analysis of genes and functional pathways for aggression in human and rodent models
title An integrated analysis of genes and functional pathways for aggression in human and rodent models
spellingShingle An integrated analysis of genes and functional pathways for aggression in human and rodent models
Zhang-James, Yanli
Genètica
Agressivitat
Genetics
Aggressiveness
title_short An integrated analysis of genes and functional pathways for aggression in human and rodent models
title_full An integrated analysis of genes and functional pathways for aggression in human and rodent models
title_fullStr An integrated analysis of genes and functional pathways for aggression in human and rodent models
title_full_unstemmed An integrated analysis of genes and functional pathways for aggression in human and rodent models
title_sort An integrated analysis of genes and functional pathways for aggression in human and rodent models
dc.creator.none.fl_str_mv Zhang-James, Yanli
Fernàndez Castillo, Noèlia
Hess, Jonathan L.
Malki, Karim
Glatt, Stephen J.
Cormand Rifà, Bru
Faraone, Stephen V.
author Zhang-James, Yanli
author_facet Zhang-James, Yanli
Fernàndez Castillo, Noèlia
Hess, Jonathan L.
Malki, Karim
Glatt, Stephen J.
Cormand Rifà, Bru
Faraone, Stephen V.
author_role author
author2 Fernàndez Castillo, Noèlia
Hess, Jonathan L.
Malki, Karim
Glatt, Stephen J.
Cormand Rifà, Bru
Faraone, Stephen V.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Genètica
Agressivitat
Genetics
Aggressiveness
topic Genètica
Agressivitat
Genetics
Aggressiveness
description Human genome-wide association studies (GWAS), transcriptome analyses of animal models, and candidate gene studies have advanced our understanding of the genetic architecture of aggressive behaviors. However, each of these methods presents unique limitations. To generate a more confident and comprehensive view of the complex genetics underlying aggression, we undertook an integrated, cross-species approach. We focused on human and rodent models to derive eight gene lists from three main categories of genetic evidence: two sets of genes identified in GWAS studies, four sets implicated by transcriptome-wide studies of rodent models, and two sets of genes with causal evidence from online Mendelian inheritance in man (OMIM) and knockout (KO) mice reports. These gene sets were evaluated for overlap and pathway enrichment to extract their similarities and differences. We identified enriched common pathways such as the G-protein coupled receptor (GPCR) signaling pathway, axon guidance, reelin signaling in neurons, and ERK/MAPK signaling. Also, individual genes were ranked based on their cumulative weights to quantify their importance as risk factors for aggressive behavior, which resulted in 40 top-ranked and highly interconnected genes. The results of our cross-species and integrated approach provide insights into the genetic etiology of aggression.
publishDate 2018
dc.date.none.fl_str_mv 2018
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/2445/166860
url https://hdl.handle.net/2445/166860
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/s41380-018-0068-7
Molecular Psychiatry, 2018, vol. 24, num. 11, p. 1655-1666
https://doi.org/10.1038/s41380-018-0068-7
info:eu-repo/grantAgreement/EC/H2020/667302
dc.rights.none.fl_str_mv (c) Zhang-James, Yanli et al., 2018
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Zhang-James, Yanli et al., 2018
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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