Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Genetic association study; Quantitative trait; Systemic sclerosis

Detalles Bibliográficos
Autores: Callejas, José Luis, Assassi, Shervin, International SSc Group, Acosta-Herrera, Marialbert, Simeón Aznar, Carmen Pilar, Kerick, Martin
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Departament de Salut de la Generalitat de Catalunya (DS)
Repositorio:Scientia. Dipòsit d'Informació Digital del Departament de Salut
OAI Identifier:oai:scientiasalut.gencat.cat:11351/8494
Acceso en línea:https://hdl.handle.net/11351/8494
Access Level:acceso abierto
Palabra clave:Expressió gènica
Esclerosi sistemàtica progressiva - Aspectes genètics
DISEASES::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic
Other subheadings::Other subheadings::Other subheadings::/genetics
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Phenomena::Genetic Structures::Transcriptome
ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémica
Otros calificadores::Otros calificadores::Otros calificadores::/genética
FENÓMENOS Y PROCESOS::fenómenos genéticos::expresión génica
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spelling Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosisCallejas, José LuisAssassi, ShervinInternational SSc GroupAcosta-Herrera, MarialbertSimeón Aznar, Carmen PilarKerick, MartinExpressió gènicaEsclerosi sistemàtica progressiva - Aspectes genèticsDISEASES::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, SystemicOther subheadings::Other subheadings::Other subheadings::/geneticsPHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Phenomena::Genetic Structures::TranscriptomeENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémicaOtros calificadores::Otros calificadores::Otros calificadores::/genéticaFENÓMENOS Y PROCESOS::fenómenos genéticos::expresión génicaGenetic association study; Quantitative trait; Systemic sclerosisEstudi d'associació genètica; Tret quantitatiu; Esclerosi sistèmicaEstudio de asociación genética; Rasgo cuantitativo; Esclerosis sistémicaCopy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals.This work was supported by grant RTI2018101332-B-100 funded by MCIN/AEI/10.13039/501100011033 by “ERDF A way of making Europe”, Red de Investigación en Inflamación y Enfermedades Reumáticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013). This work has received funding from the Innovative Medicines Initiative 1 & 2 Joint Undertaking (JU) under grant agreements No 115565 (PRECISESADS) and No 831434 (3TR). The JU receives support from the European Union’s FP7 and Horizon 2020 research and innovation programs and EFPIA. MAH was supported by the Juan de la Cierva Incorporacion program, grant IJC2018-035131-I funded by MCIN/AEI/10.13039/501100011033. This work is dedicated to the memory of Annette Kerick (1945-2020).Nature PortfolioInstitut Català de la Salut[Kerick M] Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain. [Acosta-Herrera M] Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain. Systemic Autoimmune Disease Unit, Hospital Clínico San Cecilio, Instituto de Investigación Biosanitaria Ibs. GRANADA, Granada, Spain. [Simeón-Aznar CP] Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Callejas JL] Department of Internal Medicine, Hospital San Cecilio, Granada, Spain. [Assassi S] Department of Rheumatology, The University of Texas Health Science Center at Houston, Houston, TX, USAVall d'Hebron Barcelona Hospital Campus202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/8494Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)Inglésnpj Genomic Medicine;7https://doi.org/10.1038/s41525-022-00327-8Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/84942026-06-12T09:38:37Z
dc.title.none.fl_str_mv Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
title Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
spellingShingle Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
Callejas, José Luis
Expressió gènica
Esclerosi sistemàtica progressiva - Aspectes genètics
DISEASES::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic
Other subheadings::Other subheadings::Other subheadings::/genetics
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Phenomena::Genetic Structures::Transcriptome
ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémica
Otros calificadores::Otros calificadores::Otros calificadores::/genética
FENÓMENOS Y PROCESOS::fenómenos genéticos::expresión génica
title_short Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
title_full Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
title_fullStr Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
title_full_unstemmed Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
title_sort Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis
dc.creator.none.fl_str_mv Callejas, José Luis
Assassi, Shervin
International SSc Group
Acosta-Herrera, Marialbert
Simeón Aznar, Carmen Pilar
Kerick, Martin
author Callejas, José Luis
author_facet Callejas, José Luis
Assassi, Shervin
International SSc Group
Acosta-Herrera, Marialbert
Simeón Aznar, Carmen Pilar
Kerick, Martin
author_role author
author2 Assassi, Shervin
International SSc Group
Acosta-Herrera, Marialbert
Simeón Aznar, Carmen Pilar
Kerick, Martin
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Kerick M] Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain. [Acosta-Herrera M] Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain. Systemic Autoimmune Disease Unit, Hospital Clínico San Cecilio, Instituto de Investigación Biosanitaria Ibs. GRANADA, Granada, Spain. [Simeón-Aznar CP] Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Callejas JL] Department of Internal Medicine, Hospital San Cecilio, Granada, Spain. [Assassi S] Department of Rheumatology, The University of Texas Health Science Center at Houston, Houston, TX, USA
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Expressió gènica
Esclerosi sistemàtica progressiva - Aspectes genètics
DISEASES::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic
Other subheadings::Other subheadings::Other subheadings::/genetics
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Phenomena::Genetic Structures::Transcriptome
ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémica
Otros calificadores::Otros calificadores::Otros calificadores::/genética
FENÓMENOS Y PROCESOS::fenómenos genéticos::expresión génica
topic Expressió gènica
Esclerosi sistemàtica progressiva - Aspectes genètics
DISEASES::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic
Other subheadings::Other subheadings::Other subheadings::/genetics
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Phenomena::Genetic Structures::Transcriptome
ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémica
Otros calificadores::Otros calificadores::Otros calificadores::/genética
FENÓMENOS Y PROCESOS::fenómenos genéticos::expresión génica
description Genetic association study; Quantitative trait; Systemic sclerosis
publishDate 2022
dc.date.none.fl_str_mv 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/11351/8494
url https://hdl.handle.net/11351/8494
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv npj Genomic Medicine;7
https://doi.org/10.1038/s41525-022-00327-8
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://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 Portfolio
publisher.none.fl_str_mv Nature Portfolio
dc.source.none.fl_str_mv Scientia
reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname:Departament de Salut de la Generalitat de Catalunya (DS)
instname_str Departament de Salut de la Generalitat de Catalunya (DS)
reponame_str Scientia. Dipòsit d'Informació Digital del Departament de Salut
collection Scientia. Dipòsit d'Informació Digital del Departament de Salut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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