GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways
Metadatos
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López Isac, Elena; Acosta Herrera, Marialbert; Kerick, Martin; Ortega Centeno, Norberto; Carmona López, Francisco David; Ríos, R; Callejas Rubio, José Luis; Vargas Hitos, José AntonioEditorial
Springer Nature
Fecha
2019Referencia bibliográfica
López-Isac, E., Acosta-Herrera, M., Kerick, M., Assassi, S., Satpathy, A. T., Granja, J., ... & Ortego-Centeno, N. (2019). GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways. Nature communications, 10(1), 1-14.
Patrocinador
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.Resumen
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.