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

Journal article
(Report)


Publication Details

Author(s): 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
Journal: Arthritis and Rheumatology
Publication year: 2016
Volume: 68
Journal issue: 9
Pages range: 2338-44
ISSN: 2326-5191
eISSN: 2326-5205


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.



FAU Authors / FAU Editors

Distler, Jörg PD Dr.
Heisenberg-Professur für Molekulare Mechanismen der Organfibrose


External institutions with authors

Bellvitge University Hospital / Hospital Universitari de Bellvitge
Complejo Hospitalario Universitario de Vigo (CHUVI)
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Hospital Clínico San Carlos
Hospital Clínico Universitario de Valencia
Hospital Universitario 12 de Octubre
Hospital Universitario de La Princesa
Hospital Universitario La Paz
Hospital Universitario Virgen de las Nieves
Hospital Universitario y Politécnico de La Fe
Karolinska University Hospital / Karolinska Universitetssjukhuset
Leiden University
Lund University / Lunds universitet
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Oslo universitetssykehus Rikshospitalet
Radboud University Nijmegen
Royal Free Hospital
Spanish National Research Council / Consejo Superior de Investigaciones Científicas (CSIC)
Universidad de Cantabria (UC)
Università Politecnica delle Marche (UNIVPM)
Universität Köln
Universität zu Lübeck
University Medical Centre Utrecht (UMC Utrecht)
University of Manchester
University of Otago
University of Texas Health Science Center at Houston (UTHealth)
University of Verona / Università degli Studi di Verona
Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron
Vrije Universiteit Amsterdam (VU) / University Amsterdam


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://dx.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.

BibTeX: 

Last updated on 2018-27-11 at 06:02