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

Lopez-Isac E, Martin JE, Assassi S, Simeon CP, Carreira P, Ortego-Centeno N, Freire M, Beltran E, Narvaez J, Alegre-Sancho JJ, Fernandez-Gutierrez B, Balsa A, Ortiz AM, Gonzalez-Gay MA, Beretta L, Santaniello A, Bellocchi C, Lunardi C, Moroncini G, Gabrielli A, Witte T, Hunzelmann N, Distler J, Riekemasten G, Van Der Helm-Van Mil AH, De Vries-Bouwstra J, Magro-Checa C, Voskuyl AE, Vonk MC, Molberg O, Merriman T, Hesselstrand R, Nordin A, Padyukov L, Herrick A, Eyre S, Koeleman BPC, Denton CP, Fonseca C, Radstake TRDJ, Worthington J, Mayes MD, Martin J (2016)

Publication Type: Journal article, Report

Publication year: 2016

Journal

Book Volume: 68

Pages Range: 2338-44

Journal Issue: 9

DOI: 10.1002/art.39730

Abstract

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.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.This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P < 5 × 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 (Pcombined = 3.29 × 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.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.

Authors with CRIS profile

Involved external institutions

Hospital Universitario 12 de Octubre Spain (ES) Hospital Universitario Virgen de las Nieves Spain (ES) Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico Italy (IT) Universität zu Lübeck Germany (DE) Leiden University Netherlands (NL) Vrije Universiteit Amsterdam (VU) / University Amsterdam Netherlands (NL) Radboud University Nijmegen Netherlands (NL) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) University of Otago New Zealand (NZ) Lund University / Lunds universitet Sweden (SE) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) University of Manchester United Kingdom (GB) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Royal Free Hospital United Kingdom (GB) University of Texas Health Science Center at Houston (UTHealth) United States (USA) (US) Spanish National Research Council / Consejo Superior de Investigaciones Científicas (CSIC) Spain (ES) Università Politecnica delle Marche (UNIVPM) / Marche Polytechnic University Italy (IT) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron Spain (ES) Complejo Hospitalario Universitario de Vigo (CHUVI) Spain (ES) Hospital Universitario y Politécnico de La Fe Spain (ES) Bellvitge University Hospital / Hospital Universitari de Bellvitge Spain (ES) Hospital Clínico Universitario de Valencia Spain (ES) Hospital Clínico San Carlos Spain (ES) Hospital Universitario La Paz Spain (ES) Hospital Universitario de La Princesa Spain (ES) Universidad de Cantabria (UC) Spain (ES) University of Verona / Università degli Studi di Verona Italy (IT) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Universität zu Köln Germany (DE)

How to cite

APA:

Lopez-Isac, E., Martin, J.-E., Assassi, S., Simeon, C.P., Carreira, P., Ortego-Centeno, N.,... Martin, 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 and Rheumatology, 68(9), 2338-44. https://doi.org/10.1002/art.39730

MLA:

Lopez-Isac, Elena, et al. "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 and Rheumatology 68.9 (2016): 2338-44.

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