2024-03-29T08:16:34Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1903792023-01-16T07:32:04Zcom_10261_64com_10261_1col_10261_317
IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies
López-Isac, Elena
Martin, J.E.
Assassi, S.
Simeón, Carmen P.
Carreira, P.
Ortego-Centeno, N.
Freire, María del Carmen
Beltran, E.
Narváez, Javier
Alegre-Sancho, Juan-José
Fernández-Gutiérrez, B.
Balsa, Alejandro
Ortiz, Ana María
González-Gay, M. A.
Beretta, L.
Santaniello, Alessandro
Bellocchi, Chiara
Lunardi, C.
Moroncini, Gianluca
Gabrielli, Armando
Witte, Torsten
Hunzelmann, Nicolas
Distler, J. H.
Riekemasten, Gabriella
van der Helm-Van Mil, Annette H. M.
de Vries-Bouwstra, Jeska
Magro-Checa, Cesar
Voskuyl, Alexandre E.
Vonk, Madelon C.
Molberg, Oyvind
Merriman, Tony
Hesselstrand, R.
Nordin, A.
Padyukov, Leonid
Herrick, A.
Eyre, Steve
Koeleman, B. P.
Denton, C.
Fonseca, C.
Radstake, T. R.
Worthington, J.
Mayes, Maureen D.
Martín, J.
Junta de Andalucía
Ministerio de Economía y Competitividad (España)
Ministerio de Educación, Cultura y Deporte (España)
European Commission
Dutch Association for Institutional Research
Dutch Arthritis Foundation
National Institutes of Health (US)
National Institute of Allergy and Infectious Diseases (US)
National Center for Research Resources (US)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (US)
Department of Defense (US)
Martín, J. [0000-0002-2202-0622]
Autoría conjunta: Spanish Scleroderma Grp
Objective. Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc-RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc-RA loci through an interdisease meta-genome-wide association (meta-GWAS) strategy.
Methods. The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case-control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls.
Results. This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P<5 x 10(-6)) that also showed evidence of association in the disease-specific GWAS scans. These loci included several genomic regions not previously reported as shared loci, as well as several risk factors that were previously found to be associated with both diseases. Follow-up analyses of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these 2 diseases (P-combined=3.29 x 10(-12)). Analysis of the biologic relevance of the known SSc-RA shared loci identified the type I interferon and interleukin-12 signaling pathways as the main common etiologic factors.
Conclusion. This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.
Supported by a grant from the Ministerio de Educacion, Cultura y Deporte through the program FPU (to Dr. Lopez-Isac), grant 115565 from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS (ref. no. 115565) and BIO-1395 from the Junta de Andalucia, grant PI-0590-2010 from the Consejeria de Salud y Bienestar Social, Junta de Andalucia, Spain (to Dr. Ortego-Centeno), a VIDI laureate from the Dutch Association of Research and Dutch Arthritis Foundation (to Dr. Radstake), and grant SAF2012-34435 from the Spanish Ministry of Economy and Competitiveness (to Dr. J. Martin). Dr. Assassi's work was supported by grants KL2-RR-024149-04 and K23-AR-061436 from the NIH, grant 3-UL1-RR-024148 from the NIH National Center for Research Resources, and grant U01-1U01AI09090 from the NIH National Institute of Allergy and Infectious Diseases. Dr. Mayes' work was supported by grant P50-AR-054144 from the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Centers of Research Translation, grant N01-AR-0-2251 from the NIAMS SSc Family Registry and DNA Repository, grant PR-1206877 from the Department of Defense, and grant R01-AR-055258 from the NIAMS.
Peer reviewed
2019-09-10T11:52:21Z
2019-09-10T11:52:21Z
2016-09
artículo
http://purl.org/coar/resource_type/c_6501
Arthritis and Rheumatology
2326-5191
http://hdl.handle.net/10261/190379
10.1002/art.39730
2326-5205
http://dx.doi.org/10.13039/501100003176
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/100000097
http://dx.doi.org/10.13039/100000002
http://dx.doi.org/10.13039/100000069
http://dx.doi.org/10.13039/100000005
http://dx.doi.org/10.13039/100000060
http://dx.doi.org/10.13039/501100011011
http://dx.doi.org/10.13039/100006492
27111665
en
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2012-34435
info:eu-repo/grantAgreement/EC/FP7/115565
Sí
none
John Wiley & Sons