A polygenic resilience score moderates the genetic risk for schizophrenia

Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531–538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable p...

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Autores: Hess, Jonathan L., Tylee, Daniel S., Mattheisen, Manuel, D. Børglum, Anders, D. Als, Thomas, Grove, Jakob, Crespo Facorro, Benedicto
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/135040
Acceso en línea:https://hdl.handle.net/11441/135040
https://doi.org/10.1038/s41380-019-0463-8
Access Level:acceso abierto
Palabra clave:Polygenic resilience
Schizophrenia
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spelling A polygenic resilience score moderates the genetic risk for schizophreniaHess, Jonathan L.Tylee, Daniel S.Mattheisen, ManuelD. Børglum, AndersD. Als, ThomasGrove, JakobCrespo Facorro, BenedictoPolygenic resilienceSchizophreniaBased on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531–538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known “polygenic resilience score” that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.Springer NaturePsiquiatría2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/135040https://doi.org/10.1038/s41380-019-0463-8reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésMolecular Psychiatry, 26 (3), 800-815.https://www.nature.com/articles/s41380-019-0463-8info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1350402026-06-17T12:51:07Z
dc.title.none.fl_str_mv A polygenic resilience score moderates the genetic risk for schizophrenia
title A polygenic resilience score moderates the genetic risk for schizophrenia
spellingShingle A polygenic resilience score moderates the genetic risk for schizophrenia
Hess, Jonathan L.
Polygenic resilience
Schizophrenia
title_short A polygenic resilience score moderates the genetic risk for schizophrenia
title_full A polygenic resilience score moderates the genetic risk for schizophrenia
title_fullStr A polygenic resilience score moderates the genetic risk for schizophrenia
title_full_unstemmed A polygenic resilience score moderates the genetic risk for schizophrenia
title_sort A polygenic resilience score moderates the genetic risk for schizophrenia
dc.creator.none.fl_str_mv Hess, Jonathan L.
Tylee, Daniel S.
Mattheisen, Manuel
D. Børglum, Anders
D. Als, Thomas
Grove, Jakob
Crespo Facorro, Benedicto
author Hess, Jonathan L.
author_facet Hess, Jonathan L.
Tylee, Daniel S.
Mattheisen, Manuel
D. Børglum, Anders
D. Als, Thomas
Grove, Jakob
Crespo Facorro, Benedicto
author_role author
author2 Tylee, Daniel S.
Mattheisen, Manuel
D. Børglum, Anders
D. Als, Thomas
Grove, Jakob
Crespo Facorro, Benedicto
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Psiquiatría
dc.subject.none.fl_str_mv Polygenic resilience
Schizophrenia
topic Polygenic resilience
Schizophrenia
description Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531–538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known “polygenic resilience score” that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/135040
https://doi.org/10.1038/s41380-019-0463-8
url https://hdl.handle.net/11441/135040
https://doi.org/10.1038/s41380-019-0463-8
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Molecular Psychiatry, 26 (3), 800-815.
https://www.nature.com/articles/s41380-019-0463-8
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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