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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
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, Volume 68, No. 9, Year 2016
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Description
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 × 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. 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. © 2016, American College of Rheumatology
Authors & Co-Authors
Carreira-Delgado, Patricia E.
Spain, Madrid
Hospital Universitario 12 de Octubre
Ortego-Centeno, Norberto
Spain, Granada
Hospital Universitario San Cecilio
Narváez, Javier A.
Spain, Barcelona
Hospital Universitari de Bellvitge
Alegre-Sancho, Juan José
Spain, Valencia
Hospital Universitario Dr. Peset
Fernàndez-Gutiérrez, Benjamín
Spain, Madrid
Hospital Clínico San Carlos
Balsa, Alejando
Spain, Madrid
Instituto de Investigación Sanitaria Del Hospital Universitario la Paz
González-Gay, Miguel Ángel
Spain, Santander
Universidad de Cantabria
Beretta, Lorenzo
Italy, Milan
Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
Moroncini, Gianluca
Italy, Ancona
Azienda Ospedaliera Universitaria Ospedali Riuniti, Ancona
Gabrielli, Armando
Italy, Ancona
Azienda Ospedaliera Universitaria Ospedali Riuniti, Ancona
Witte, Torsten
Germany, Hannover
Hannover Medical School
Hunzelmann, Nicolas
Germany, Koln
Universität zu Köln
Distler, Jor̈g H.W.
Germany, Erlangen
Friedrich-alexander-universität Erlangen-nürnberg
van der Helm – van Mil, Annette H.Mvan
Netherlands, Leiden
Leids Universitair Medisch Centrum
Magro-Checa, César
Netherlands, Leiden
Leids Universitair Medisch Centrum
Voskuyl, Alexandre E.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Vonk, Madelon C.
Netherlands, Nijmegen
Radboud University Medical Center
Merriman, Tony R.
New Zealand, Dunedin
University of Otago
Hesselstrand, Roger
Sweden, Lund
Lunds Universitet
Padyukov, Leonid
Sweden, Stockholm
Karolinska Institutet
Herrick, Ariane L.
United Kingdom, Manchester
Health Innovation Manchester
Eyre, Stephen
United Kingdom, Manchester
Health Innovation Manchester
Koeleman, Bobby P.C.
Netherlands, Utrecht
University Medical Center Utrecht
Denton, Christopher Paul
United Kingdom, London
Ucl Medical School
Radstake, Timothy R.D.J.
Netherlands, Utrecht
University Medical Center Utrecht
Mayes, Maureen Davidica
United States, Houston
University of Texas Health Science Center at Houston
Martin, Javier
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Callejas-Rubio, José Luís
Unknown Affiliation
Fernández-Nebro, Antonio
Unknown Affiliation
Gónzalez-Escribano, María Francisca
Unknown Affiliation
Rodríguez-Rodríguez, Luís Pablo
Unknown Affiliation
Vicente-Rabaneda, Esther Francisca
Unknown Affiliation
Andréu, José Luis
Unknown Affiliation
López-Longo, Francisco Javier
Unknown Affiliation
Espinosa, Gerard
Unknown Affiliation
Ortiz-Santamaría, Vera
Unknown Affiliation
Díaz-González, Federico J.
Unknown Affiliation
Blanco, F. J.
Unknown Affiliation
Statistics
Citations: 40
Authors: 38
Affiliations: 30
Identifiers
Doi:
10.1002/art.39730
ISSN:
23265191
Research Areas
Genetics And Genomics
Study Design
Cohort Study
Study Approach
Systematic review