A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium

Identifying heritable factors that moderate the genetic risk for schizophrenia (SCZ) could help clarify why some individuals remain unaffected despite having relatively high genetic liability. Previously, we developed a framework to mine genome-wide association (GWAS) data for common genetic variant...

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Autores: Hess, Jonathan, Mattheisen, Manuel, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Greenwood, Tiffany A., Tsuang, Ming T, Edenberg, Howard J., Holmans, Peter, Faraone, Stephen V., Glatt, Stephen J., Fañanas Saura, Lourdes
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2023
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/227934
Acesso em linha:https://hdl.handle.net/2445/227934
Access Level:Acceso aberto
Palavra-chave:Escales d'avaluació psiquiàtrica
Epidemiologia genètica
Esquizofrènia
Psychiatric rating scales
Genetic epidemiology
Schizophrenia
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spelling A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics ConsortiumHess, JonathanMattheisen, ManuelSchizophrenia Working Group of the Psychiatric Genomics ConsortiumGreenwood, Tiffany A.Tsuang, Ming TEdenberg, Howard J.Holmans, PeterFaraone, Stephen V.Glatt, Stephen J.Fañanas Saura, LourdesEscales d'avaluació psiquiàtricaEpidemiologia genèticaEsquizofrèniaPsychiatric rating scalesGenetic epidemiologySchizophreniaIdentifying heritable factors that moderate the genetic risk for schizophrenia (SCZ) could help clarify why some individuals remain unaffected despite having relatively high genetic liability. Previously, we developed a framework to mine genome-wide association (GWAS) data for common genetic variants that protect high-risk unaffected individuals from SCZ, leading to derivation of the first-ever "polygenic resilience score" for SCZ (resilient controls n = 3786; polygenic risk score-matched SCZ cases n = 18,619). Here, we performed a replication study to verify the moderating effect of our polygenic resilience score on SCZ risk (OR = 1.09, p = 4.03 × 10-5 ) using newly released GWAS data from 23 independent case-control studies collated by the Psychiatric Genomics Consortium (PGC) (resilient controls n = 2821; polygenic risk score-matched SCZ cases n = 5150). Additionally, we sought to optimize our polygenic resilience-scoring formula to improve subsequent modeling of resilience to SCZ and other complex disorders. We found significant replication of the polygenic resilience score, and found that strict pruning of SNPs based on linkage disequilibrium to known risk SNPs and their linked loci optimizes the performance of the polygenic resilience score.Wiley-Liss2026202620232026info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion44 p.application/pdfhttps://hdl.handle.net/2445/227934Articles publicats en revistes (Biologia Evolutiva, Ecologia i Ciències Ambientals)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1002/ajmg.b.32957American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2023, vol. 195, num.2https://doi.org/10.1002/ajmg.b.32957(c) Wiley-Liss, 2023info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2279342026-05-29T05:05:01Z
dc.title.none.fl_str_mv A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium
title A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium
spellingShingle A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium
Hess, Jonathan
Escales d'avaluació psiquiàtrica
Epidemiologia genètica
Esquizofrènia
Psychiatric rating scales
Genetic epidemiology
Schizophrenia
title_short A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium
title_full A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium
title_fullStr A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium
title_full_unstemmed A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium
title_sort A Polygenic Resilience Score Moderates the Genetic Risk for Schizophrenia: Replication in 18,090 Cases and 28,114 Controls from the Psychiatric Genomics Consortium
dc.creator.none.fl_str_mv Hess, Jonathan
Mattheisen, Manuel
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Greenwood, Tiffany A.
Tsuang, Ming T
Edenberg, Howard J.
Holmans, Peter
Faraone, Stephen V.
Glatt, Stephen J.
Fañanas Saura, Lourdes
author Hess, Jonathan
author_facet Hess, Jonathan
Mattheisen, Manuel
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Greenwood, Tiffany A.
Tsuang, Ming T
Edenberg, Howard J.
Holmans, Peter
Faraone, Stephen V.
Glatt, Stephen J.
Fañanas Saura, Lourdes
author_role author
author2 Mattheisen, Manuel
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Greenwood, Tiffany A.
Tsuang, Ming T
Edenberg, Howard J.
Holmans, Peter
Faraone, Stephen V.
Glatt, Stephen J.
Fañanas Saura, Lourdes
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Escales d'avaluació psiquiàtrica
Epidemiologia genètica
Esquizofrènia
Psychiatric rating scales
Genetic epidemiology
Schizophrenia
topic Escales d'avaluació psiquiàtrica
Epidemiologia genètica
Esquizofrènia
Psychiatric rating scales
Genetic epidemiology
Schizophrenia
description Identifying heritable factors that moderate the genetic risk for schizophrenia (SCZ) could help clarify why some individuals remain unaffected despite having relatively high genetic liability. Previously, we developed a framework to mine genome-wide association (GWAS) data for common genetic variants that protect high-risk unaffected individuals from SCZ, leading to derivation of the first-ever "polygenic resilience score" for SCZ (resilient controls n = 3786; polygenic risk score-matched SCZ cases n = 18,619). Here, we performed a replication study to verify the moderating effect of our polygenic resilience score on SCZ risk (OR = 1.09, p = 4.03 × 10-5 ) using newly released GWAS data from 23 independent case-control studies collated by the Psychiatric Genomics Consortium (PGC) (resilient controls n = 2821; polygenic risk score-matched SCZ cases n = 5150). Additionally, we sought to optimize our polygenic resilience-scoring formula to improve subsequent modeling of resilience to SCZ and other complex disorders. We found significant replication of the polygenic resilience score, and found that strict pruning of SNPs based on linkage disequilibrium to known risk SNPs and their linked loci optimizes the performance of the polygenic resilience score.
publishDate 2023
dc.date.none.fl_str_mv 2023
2026
2026
2026
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/2445/227934
url https://hdl.handle.net/2445/227934
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/10.1002/ajmg.b.32957
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2023, vol. 195, num.2
https://doi.org/10.1002/ajmg.b.32957
dc.rights.none.fl_str_mv (c) Wiley-Liss, 2023
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Wiley-Liss, 2023
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 44 p.
application/pdf
dc.publisher.none.fl_str_mv Wiley-Liss
publisher.none.fl_str_mv Wiley-Liss
dc.source.none.fl_str_mv Articles publicats en revistes (Biologia Evolutiva, Ecologia i Ciències Ambientals)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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