Journal article

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

Elena Lopez-Isac, Marialbert Acosta-Herrera, Martin Kerick, Shervin Assassi, Ansuman T Satpathy, Jeffrey Granja, Maxwell R Mumbach, Lorenzo Beretta, Carmen P Simeon, Patricia Carreira, Norberto Ortego-Centeno, Ivan Castellvi, Lara Bossini-Castillo, F David Carmona, Gisela Orozco, Nicolas Hunzelmann, Joerg HW Distler, Andre Franke, Claudio Lunardi, Gianluca Moroncini Show all

Nature Communications | NATURE PUBLISHING GROUP | Published : 2019

Abstract

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 targ..

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Grants

Awarded by Spanish Ministry of Economy and Competitiveness


Awarded by Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucia


Awarded by Ministerio de Educacion, Cultura y Deporte


Awarded by Red de Investigacion en Inflamacion y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III


Awarded by NIH


Awarded by German Ministry for Education and Research



Funding Acknowledgements

We thank Sofia Vargas, Sonia Garcia, and Gema Robledo for their excellent technical assistance and all the patients and control donors for their essential collaboration. We thank National DNA Bank Carlos III (University of Salamanca, Spain) that supplied part of the control DNA samples from Spain, WTCCC and EIRA Consortiums, and PopGen 2.0 network. This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucia (P12-BIO-1395), Ministerio de Educacion, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigacion en Inflamacion y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50HG007735 (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.