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    Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

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    23. Lopez-Isaac.pdf (1.043Mb)
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    URI: http://hdl.handle.net/10902/11560
    DOI: 10.1002/art.39730
    ISSN: 2326-5205
    ISSN: 2326-5191
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    Author
    López Isac, Elena; Martín, Jose Ezequiel; Assassi, Shervin; Simeón Aznar, Carmen Pilar; Carreira, Patricia; Ortego Centeno, Norberto; Freire, Mayka; Beltrán, Emma; Narváez, Javier; Alegre Sancho, Juan J.; Spanish Scleroderma Group; Fernández Gutiérrez, Benjamín; Balsa Criado, Alejandro; Ortiz, Ana M.; González-Gay Mantecón, Miguel ÁngelAutoridad Unican; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; [et al.]
    Date
    2016-04-19
    Derechos
    ©John Wiley & Sons. This is the peer reviewed version of the following article: López-Isac, E., Martín, J.-E., Assassi, S., Simeón, C. P., Carreira, P., Ortego-Centeno, N., Freire, M., Beltrán, E., Narváez, J., Alegre-Sancho, J. J., the Spanish Scleroderma Group, Fernández-Gutiérrez, B., Balsa, A., Ortiz, A. M., González-Gay, M. A., Beretta, L., Santaniello, A., Bellocchi, C., Lunardi, C., Moroncini, G., Gabrielli, A., Witte, T., Hunzelmann, N., Distler, J. H. W., Riekemasten, G., van der Helm-van Mil, A. H., de Vries-Bouwstra, J., Magro-Checa, C., Voskuyl, A. E., Vonk, M. C., Molberg, Ø., Merriman, T., Hesselstrand, R., Nordin, A., Padyukov, L., Herrick, A., Eyre, S., Koeleman, B. P. C., Denton, C. P., Fonseca, C., Radstake, T. R. D. J., Worthington, J., Mayes, M. D. and Martín, J. (2016), Brief Report: 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. Arthritis & Rheumatology, 68: 2338-2344, which has been published in final form at doi:10.1002/art.39730. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."
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    Arthritis & Rheumatology 2016 DOI 10.1002/art.39730
    Publisher
    John Wiley and Sons Ltd
    Abstract:
    Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci.
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    UNIVERSIDAD DE CANTABRIA

    Repositorio realizado por la Biblioteca Universitaria utilizando DSpace software
    Contact Us | Send Feedback
    Metadatos sujetos a:licencia de Creative Commons Reconocimiento 3.0 España