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dc.contributor.authorLópez-Isac, Elena
dc.contributor.authorAcosta-Herrera, Marialbert
dc.contributor.authorKerick Martin
dc.contributor.authorAssassi, Shervin
dc.contributor.authorSatpathy, Ansuman T.
dc.contributor.authorGranja, Jeffrey
dc.contributor.authorMumbach, Maxwell R.
dc.contributor.authorBeretta, Lorenzo
dc.contributor.authorSimeón, Carmen P.
dc.contributor.authorCarreira, Patricia
dc.contributor.authorOrtego-Centeno, Norberto
dc.contributor.authorCastellvi, Ivan
dc.contributor.authorBossini-Castillo, Lara
dc.contributor.authorCarmona, F. David
dc.contributor.authorOrozco, Gisela
dc.contributor.authorHunzelmann, Nicolas
dc.contributor.authorDistler, Jörg H.W.
dc.contributor.authorFranke, Andre
dc.contributor.authorLunardi, Claudio
dc.contributor.authorGonzález-Gay Mantecón, Miguel Ángel 
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.description.abstractSystemic 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.es_ES
dc.description.sponsorshipFunding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively.es_ES
dc.format.extent14 p.es_ES
dc.publisherNature Publishing Groupes_ES
dc.rightsAttribution 4.0 Internationales_ES
dc.sourceNat Commun . 2019 Oct 31;10(1):4955es_ES
dc.titleGWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathwayses_ES

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Attribution 4.0 InternationalExcept where otherwise noted, this item's license is described as Attribution 4.0 International