GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways
Year: 2019
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Authors: 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, European Scleroderma Group†, R. Ríos, J. L. Callejas, J. A. Vargas-Hitos, R. García-Portales, M. T. Camps, A. Fernández-Nebro, M. F. González-Escribano, F. J. García-Hernández, M. J. Castillo, M. A. Aguirre, I. Gómez-Gracia, B. Fernández-Gutiérrez, L. Rodríguez-Rodríguez, P. García de la Peña, E. Vicente, J. L. Andreu, M Fernández de Castro, F. J. López-Longo, L. Martínez, Fonollosa, A. Guillén, G. Espinosa, C. Tolosa, A. Pros, M. Rodríguez-Carballeira, F. J. Narváez, M. Rubio-Rivas, Ortiz-Santamaría, A. B. Madroñero, M. A. González-Gay, B. Díaz, L. Trapiella, A. Sousa, M. V. Egurbide, P. Fanlo-Mateo, L. Sáez-Comet, F. Díaz, Hernández, E. Beltrán, J. A. Román-Ivorra, E. Grau, J. J. Alegre-Sancho, M. Freire, F. J. Blanco-García, N. Oreiro, T. Witte, A. Kreuter, G. Riemekasten, P. Airó, C. Magro, A. E. Voskuyl, M. C. Vonk, R. Hesselstrand, Susanna Proudman, Wendy Stevens, Mandana Nikpour, Australian Scleroderma Interest Group (ASIG), J. Zochling, J. Sahhar, J. Roddy, P. Nash, K. Tymms, M. Rischmueller, S. Lester, 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, Javier Martin
Institutions: Consejo Superior de Investigaciones Científicas, Instituto de Parasitología y Biomedicina "López - Neyra", The University of Texas Health Science Center at Houston, Howard Hughes Medical Institute, Stanford Medicine, Stanford University, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Vall d'Hebron Hospital Universitari, Research Institute Hospital 12 de Octubre, Hospital Universitario 12 De Octubre, Hospital de Sant Pau, Wellcome Sanger Institute, Universidad de Granada, Manchester Academic Health Science Centre, University of Manchester, University of Cologne, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Christian-Albrechts-Universität zu Kiel, University of Verona, Marche Polytechnic University, Leiden University Medical Center, University Medical Center Groningen, University of Groningen, University Medical Center Utrecht, Karolinska University Hospital, Karolinska Institutet, Oslo University Hospital, University of Oslo, Hospital Universitario Virgen de las Nieves, Hospital Clínico Universitario Virgen de la Victoria, Hospital Universitario Virgen del Rocío, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Clínico San Carlos, Hospital Universitario HM Sanchinarro, Hospital Universitario de La Princesa, Hospital Universitario Puerta de Hierro Majadahonda, Hospital General Universitario Gregorio Marañón, Hospital Clínic de Barcelona, Corporació Sanitària Parc Taulí, Hospital Del Mar, University Hospital Mútua de Terrassa, Bellvitge University Hospital, Hospital General de Granollers, Hospital General San Jorge, Universidad de Cantabria, Instituto de Investigación Marqués de Valdecilla, Hospital Universitario Central de Asturias, University Hospital Complex Of Vigo, Hospital de Cruces, Hospital Virgen del Camino, Hospital Universitario Miguel Servet, Hospital Universitario de Canarias, Hospital General Universitario De Valencia, Hospital Universitari i Politècnic La Fe, Hospital Universitario Doctor Peset, Instituto de Investigación Biomédica de A Coruña, Medizinische Hochschule Hannover, St. Josef-Hospital, Ruhr University Bochum, University of Lübeck, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Amsterdam UMC Location Vrije Universiteit Amsterdam, Radboud University Nijmegen, Radboud University Medical Center, Lund University, Royal Adelaide Hospital, The University of Adelaide, St Vincent's Hospital Melbourne, The University of Melbourne, University of Tasmania, Monash Medical Centre, Monash Health, Royal Perth Hospital, Queen Elizabeth Hospital, King's College London, NIHR Manchester Biomedical Research Centre, Salford Royal NHS Foundation Trust, The Royal Free Hospital, University College London, Inserm, Hôpital Cochin, Institut Cochin, Université Paris Descartes, Translational Research Institute, Queensland University of Technology, Princess Alexandra Hospital, Utrecht University
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: Howard Hughes Medical Institute, Wellcome Trust, Ministerio de Educación, Cultura y Deporte, Ministerio de Economía y Competitividad, Junta de Andalucía, Versus Arthritis, National Institutes of Health, Instituto de Salud Carlos III, National Human Genome Research Institute, National Center for Advancing Translational Sciences
OpenAlex ID: W2982511147