Lopez-Isac, Elena ORCID: 0000-0001-8806-5148, Martin, Jose-Ezequiel, Assassi, Shervin, Simeon, Carmen P., Carreira, Patricia, Ortego-Centeno, Norberto, Freire, Mayka, Beltran, Emma, Narvaez, Javier ORCID: 0000-0002-1614-8064, Alegre-Sancho, Juan J., Fernandez-Gutierrez, Benjamin, Balsa, Alejandro, Ortiz, Ana M., Gonzalez-Gay, Miguel A., Beretta, Lorenzo ORCID: 0000-0002-6529-6258, Santaniello, Alessandro, Bellocchi, Chiara, Lunardi, Claudio, Moroncini, Gianluca, Gabrielli, Armando, Witte, Torsten, Hunzelmann, Nicolas, Distler, Jorg H. W., Riekemasten, Gabriella, van der Helm-Van Mil, Annette H., de Vries-Bouwstra, Jeska, Magro-Checa, Cesar, Voskuyl, Alexandre E., Vonk, Madelon C., Molberg, Oyvind, Merriman, Tony ORCID: 0000-0003-0844-8726, Hesselstrand, Roger, Nordin, Annika ORCID: 0000-0003-1976-4679, Padyukov, Leonid ORCID: 0000-0003-2950-5670, Herrick, Ariane, Eyre, Steve, Koeleman, Bobby P. C., Denton, Christopher P., Fonseca, Carmen, Radstake, Timothy R. D. J., Worthington, Jane, Mayes, Maureen D. and Martin, Javier ORCID: 0000-0002-2202-0622 (2016). 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 Rheumatol., 68 (9). S. 2338 - 2345. HOBOKEN: WILEY-BLACKWELL. ISSN 2326-5205

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lopez-Isac, ElenaUNSPECIFIEDorcid.org/0000-0001-8806-5148UNSPECIFIED
Martin, Jose-EzequielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assassi, ShervinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simeon, Carmen P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carreira, PatriciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortego-Centeno, NorbertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freire, MaykaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beltran, EmmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Narvaez, JavierUNSPECIFIEDorcid.org/0000-0002-1614-8064UNSPECIFIED
Alegre-Sancho, Juan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez-Gutierrez, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balsa, AlejandroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortiz, Ana M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez-Gay, Miguel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beretta, LorenzoUNSPECIFIEDorcid.org/0000-0002-6529-6258UNSPECIFIED
Santaniello, AlessandroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bellocchi, ChiaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lunardi, ClaudioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moroncini, GianlucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabrielli, ArmandoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witte, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunzelmann, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Distler, Jorg H. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riekemasten, GabriellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Helm-Van Mil, Annette H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Vries-Bouwstra, JeskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Magro-Checa, CesarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voskuyl, Alexandre E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vonk, Madelon C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Molberg, OyvindUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merriman, TonyUNSPECIFIEDorcid.org/0000-0003-0844-8726UNSPECIFIED
Hesselstrand, RogerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nordin, AnnikaUNSPECIFIEDorcid.org/0000-0003-1976-4679UNSPECIFIED
Padyukov, LeonidUNSPECIFIEDorcid.org/0000-0003-2950-5670UNSPECIFIED
Herrick, ArianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eyre, SteveUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koeleman, Bobby P. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denton, Christopher P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fonseca, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radstake, Timothy R. D. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Worthington, JaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayes, Maureen D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, JavierUNSPECIFIEDorcid.org/0000-0002-2202-0622UNSPECIFIED
URN: urn:nbn:de:hbz:38-265325
DOI: 10.1002/art.39730
Journal or Publication Title: Arthritis Rheumatol.
Volume: 68
Number: 9
Page Range: S. 2338 - 2345
Date: 2016
Publisher: WILEY-BLACKWELL
Place of Publication: HOBOKEN
ISSN: 2326-5205
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
AUTOIMMUNE-DISEASES; PATHWAYSMultiple languages
RheumatologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26532

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