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

Elena López-Isac (), Marialbert Acosta-Herrera, Martin Kerick, Shervin Assassi, Ansuman T. Satpathy, Jeffrey Granja, Maxwell R. Mumbach, Lorenzo Beretta, Carmen P. Simeón, Patricia Carreira, Norberto Ortego-Centeno, Ivan Castellvi, Lara Bossini-Castillo, F. David Carmona, Gisela Orozco, Nicolas Hunzelmann, Jörg H. W. Distler, Andre Franke, Claudio Lunardi, Gianluca Moroncini, Armando Gabrielli, Jeska de Vries-Bouwstra, Cisca Wijmenga, Bobby P. C. Koeleman, Annika Nordin, Leonid Padyukov, Anna-Maria Hoffmann-Vold, Benedicte Lie, Susanna Proudman, Wendy Stevens, Mandana Nikpour, Timothy Vyse, Ariane L. Herrick, Jane Worthington, Christopher P. Denton, Yannick Allanore, Matthew A. Brown, Timothy R. D. J. Radstake, Carmen Fonseca, Howard Y. Chang, Maureen D. Mayes and Javier Martin ()
Additional contact information
Elena López-Isac: Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC
Marialbert Acosta-Herrera: Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC
Martin Kerick: Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC
Shervin Assassi: The University of Texas Health Science Center–Houston
Ansuman T. Satpathy: Stanford University School of Medicine
Jeffrey Granja: Stanford University School of Medicine
Maxwell R. Mumbach: Stanford University School of Medicine
Lorenzo Beretta: Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano
Carmen P. Simeón: Valle de Hebrón Hospital
Patricia Carreira: 12 de Octubre University Hospital
Norberto Ortego-Centeno: San Cecilio Clinic University Hospital
Ivan Castellvi: Santa Creu i Sant Pau University Hospital
Lara Bossini-Castillo: Wellcome Trust Sanger Institute
F. David Carmona: University of Granada
Gisela Orozco: The University of Manchester
Nicolas Hunzelmann: University of Cologne
Jörg H. W. Distler: University of Erlangen-Nuremberg
Andre Franke: Christian-Albrechts-University of Kiel
Claudio Lunardi: Università degli Studi di Verona
Gianluca Moroncini: Università Politecnica delle Marche and Ospedali Riuniti
Armando Gabrielli: Università Politecnica delle Marche and Ospedali Riuniti
Jeska de Vries-Bouwstra: Leiden University Medical Center
Cisca Wijmenga: University Medical Center Groningen, University of Groningen
Bobby P. C. Koeleman: University Medical Center Utrecht
Annika Nordin: Karolinska University Hospital, Karolinska Institute
Leonid Padyukov: Karolinska University Hospital, Karolinska Institute
Anna-Maria Hoffmann-Vold: Oslo University Hospital
Benedicte Lie: University of Oslo and Oslo University Hospital
Susanna Proudman: Royal Adelaide Hospital and University of Adelaide
Wendy Stevens: St. Vincent’s Hospital
Mandana Nikpour: The University of Melbourne at St. Vincent’s Hospital
Timothy Vyse: King’s College London
Ariane L. Herrick: The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre
Jane Worthington: The University of Manchester
Christopher P. Denton: Royal Free and University College Medical School
Yannick Allanore: INSERM U1016, Paris Descartes University
Matthew A. Brown: Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital
Timothy R. D. J. Radstake: University Medical Center Utrecht
Carmen Fonseca: Royal Free and University College Medical School
Howard Y. Chang: Stanford University School of Medicine
Maureen D. Mayes: The University of Texas Health Science Center–Houston
Javier Martin: Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-12760-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12760-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-12760-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().