Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/191024
Title: | GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways |
Author: | 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 Castellvi, 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 |
Keywords: | Esclerodèrmia Genomes Àcids nucleics Polimorfisme genètic Scleroderma (Disease) Genomes Nucleic acids Genetic polymorphisms |
Issue Date: | 31-Oct-2019 |
Publisher: | Nature Publishing Group |
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 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-019-12760-y |
It is part of: | Nature Communications, 2019, vol. 10, num. 1 |
URI: | http://hdl.handle.net/2445/191024 |
Related resource: | https://doi.org/10.1038/s41467-019-12760-y |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
693976.pdf | 1.24 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License