GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

López Isac, Elena; Acosta Herrera, Marialbert; Kerick, Martin; Assassi, Shervin; Satpathy, Ansuman T.; Granja, Jeffrey; Mumbach, Maxwell R.; Beretta, Lorenzo; Simeón Aznar, Carmen Pilar; Carreira, Patricia; Ortego Centeno, Norberto; Castellví, Ivan; Bossini Castillo, Lara; Carmona, F. David; Orozco, Gisela; Hunzelmann, Nicolas; Distler, Jörg H.V.; Franke, Andre; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Vries-Bouwstra, Jeska de; Wijmenga, Cisca; Koeleman, Bobby P. C.; Nordin, Annika; Padyukov, Leonid; Hoffmann-Vold, Anna-Maria; Lie, Benedicte; European Scleroderma Group; Proudman, Susanna; Stevens, Stevens; Nikpour, Mandana; Australian Scleroderma Interest Group (ASIG); Vyse, Timothy; Herrick, Ariane L.; Worthington, Jane; Denton, Christopher P.; Allanore, Yannick; Brown, Matthew A.; Radstake, Timothy R.D.J.; Fonseca, Carmen; Chang, Howard Y.; Mayes, Maureen D.; Martin, Javier; Narváez García, Francisco Javier

GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals,...

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Autores:	López Isac, Elena, Acosta Herrera, Marialbert, Kerick, Martin, Assassi, Shervin, Satpathy, Ansuman T., Granja, Jeffrey, Mumbach, Maxwell R., Beretta, Lorenzo, Simeón Aznar, Carmen Pilar, Carreira, Patricia, Ortego Centeno, Norberto, Castellví, Ivan, Bossini Castillo, Lara, Carmona, F. David, Orozco, Gisela, Hunzelmann, Nicolas, Distler, Jörg H.V., Franke, Andre, Lunardi, Claudio, Moroncini, Gianluca, Gabrielli, Armando, Vries-Bouwstra, Jeska de, Wijmenga, Cisca, Koeleman, Bobby P. C., Nordin, Annika, Padyukov, Leonid, Hoffmann-Vold, Anna-Maria, Lie, Benedicte, European Scleroderma Group, Proudman, Susanna, Stevens, Stevens, Nikpour, Mandana, Australian Scleroderma Interest Group (ASIG), Vyse, Timothy, Herrick, Ariane L., Worthington, Jane, Denton, Christopher P., Allanore, Yannick, Brown, Matthew A., Radstake, Timothy R.D.J., Fonseca, Carmen, Chang, Howard Y., Mayes, Maureen D., Martin, Javier, Narváez García, Francisco Javier
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2019
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/191024
Acceso en línea:	https://hdl.handle.net/2445/191024
Access Level:	acceso abierto
Palabra clave:	Esclerodèrmia Genomes Àcids nucleics Polimorfisme genètic Scleroderma (Disease) Nucleic acids Genetic polymorphisms

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spelling	GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathwaysLópez Isac, ElenaAcosta Herrera, MarialbertKerick, MartinAssassi, ShervinSatpathy, Ansuman T.Granja, JeffreyMumbach, Maxwell R.Beretta, LorenzoSimeón Aznar, Carmen PilarCarreira, PatriciaOrtego Centeno, NorbertoCastellví, IvanBossini Castillo, LaraCarmona, F. DavidOrozco, GiselaHunzelmann, NicolasDistler, Jörg H.V.Franke, AndreLunardi, ClaudioMoroncini, GianlucaGabrielli, ArmandoVries-Bouwstra, Jeska deWijmenga, CiscaKoeleman, Bobby P. C.Nordin, AnnikaPadyukov, LeonidHoffmann-Vold, Anna-MariaLie, BenedicteEuropean Scleroderma GroupProudman, SusannaStevens, StevensNikpour, MandanaAustralian Scleroderma Interest Group (ASIG)Vyse, TimothyHerrick, Ariane L.Worthington, JaneDenton, Christopher P.Allanore, YannickBrown, Matthew A.Radstake, Timothy R.D.J.Fonseca, CarmenChang, Howard Y.Mayes, Maureen D.Martin, JavierNarváez García, Francisco JavierEsclerodèrmiaGenomesÀcids nucleicsPolimorfisme genèticScleroderma (Disease)GenomesNucleic acidsGenetic polymorphismsSystemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Nature Publishing Group2022202220192022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/191024Articles publicats en revistes (Ciències Clíniques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41467-019-12760-yNature Communications, 2019, vol. 10, num. 1https://doi.org/10.1038/s41467-019-12760-ycc-by (c) López Isac, Elena et al., 2019https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1910242026-05-29T05:05:01Z
dc.title.none.fl_str_mv	GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways
title	GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways
spellingShingle	GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways López Isac, Elena Esclerodèrmia Genomes Àcids nucleics Polimorfisme genètic Scleroderma (Disease) Genomes Nucleic acids Genetic polymorphisms
title_short	GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways
title_full	GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways
title_fullStr	GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways
title_full_unstemmed	GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways
title_sort	GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways
dc.creator.none.fl_str_mv	López Isac, Elena Acosta Herrera, Marialbert Kerick, Martin Assassi, Shervin Satpathy, Ansuman T. Granja, Jeffrey Mumbach, Maxwell R. Beretta, Lorenzo Simeón Aznar, Carmen Pilar Carreira, Patricia Ortego Centeno, Norberto Castellví, Ivan Bossini Castillo, Lara Carmona, F. David Orozco, Gisela Hunzelmann, Nicolas Distler, Jörg H.V. Franke, Andre Lunardi, Claudio Moroncini, Gianluca Gabrielli, Armando Vries-Bouwstra, Jeska de Wijmenga, Cisca Koeleman, Bobby P. C. Nordin, Annika Padyukov, Leonid Hoffmann-Vold, Anna-Maria Lie, Benedicte European Scleroderma Group Proudman, Susanna Stevens, Stevens Nikpour, Mandana Australian Scleroderma Interest Group (ASIG) Vyse, Timothy Herrick, Ariane L. Worthington, Jane Denton, Christopher P. Allanore, Yannick Brown, Matthew A. Radstake, Timothy R.D.J. Fonseca, Carmen Chang, Howard Y. Mayes, Maureen D. Martin, Javier Narváez García, Francisco Javier
author	López Isac, Elena
author_facet	López Isac, Elena Acosta Herrera, Marialbert Kerick, Martin Assassi, Shervin Satpathy, Ansuman T. Granja, Jeffrey Mumbach, Maxwell R. Beretta, Lorenzo Simeón Aznar, Carmen Pilar Carreira, Patricia Ortego Centeno, Norberto Castellví, Ivan Bossini Castillo, Lara Carmona, F. David Orozco, Gisela Hunzelmann, Nicolas Distler, Jörg H.V. Franke, Andre Lunardi, Claudio Moroncini, Gianluca Gabrielli, Armando Vries-Bouwstra, Jeska de Wijmenga, Cisca Koeleman, Bobby P. C. Nordin, Annika Padyukov, Leonid Hoffmann-Vold, Anna-Maria Lie, Benedicte European Scleroderma Group Proudman, Susanna Stevens, Stevens Nikpour, Mandana Australian Scleroderma Interest Group (ASIG) Vyse, Timothy Herrick, Ariane L. Worthington, Jane Denton, Christopher P. Allanore, Yannick Brown, Matthew A. Radstake, Timothy R.D.J. Fonseca, Carmen Chang, Howard Y. Mayes, Maureen D. Martin, Javier Narváez García, Francisco Javier
author_role	author
author2	Acosta Herrera, Marialbert Kerick, Martin Assassi, Shervin Satpathy, Ansuman T. Granja, Jeffrey Mumbach, Maxwell R. Beretta, Lorenzo Simeón Aznar, Carmen Pilar Carreira, Patricia Ortego Centeno, Norberto Castellví, Ivan Bossini Castillo, Lara Carmona, F. David Orozco, Gisela Hunzelmann, Nicolas Distler, Jörg H.V. Franke, Andre Lunardi, Claudio Moroncini, Gianluca Gabrielli, Armando Vries-Bouwstra, Jeska de Wijmenga, Cisca Koeleman, Bobby P. C. Nordin, Annika Padyukov, Leonid Hoffmann-Vold, Anna-Maria Lie, Benedicte European Scleroderma Group Proudman, Susanna Stevens, Stevens Nikpour, Mandana Australian Scleroderma Interest Group (ASIG) Vyse, Timothy Herrick, Ariane L. Worthington, Jane Denton, Christopher P. Allanore, Yannick Brown, Matthew A. Radstake, Timothy R.D.J. Fonseca, Carmen Chang, Howard Y. Mayes, Maureen D. Martin, Javier Narváez García, Francisco Javier
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Esclerodèrmia Genomes Àcids nucleics Polimorfisme genètic Scleroderma (Disease) Genomes Nucleic acids Genetic polymorphisms
topic	Esclerodèrmia Genomes Àcids nucleics Polimorfisme genètic Scleroderma (Disease) Genomes Nucleic acids Genetic polymorphisms
description	Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.
publishDate	2019
dc.date.none.fl_str_mv	2019 2022 2022 2022
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/2445/191024
url	https://hdl.handle.net/2445/191024
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1038/s41467-019-12760-y Nature Communications, 2019, vol. 10, num. 1 https://doi.org/10.1038/s41467-019-12760-y
dc.rights.none.fl_str_mv	cc-by (c) López Isac, Elena et al., 2019 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by (c) López Isac, Elena et al., 2019 https://creativecommons.org/licenses/by/4.0/
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 (Ciències Clíniques) 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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GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

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