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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Detalles Bibliográficos
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
Descripción
Sumario: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.

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