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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

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 ofcommon risk loci.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Arthritis & Rheumatology 2016 DOI 10.1002/art.39730

Editorial: John Wiley and Sons Ltd

 Fecha de publicación: 19/04/2016

Nº de páginas: 23

Tipo de publicación: Artículo de Revista

 DOI: 10.1002/art.39730

ISSN: 2326-5205,2326-5191

Autores/as

LÓPEZ ISAC, ELENA

MARTÍN, JOSE EZEQUIEL

ASSASSI, SHERVIN

SIMEÓN, CARMEN P.

CARREIRA, PATRICIA

ORTEGO CENTENO, NORBERTO

FREIRE, MAYKA

BELTRÁN, EMMA

NARVÁEZ, JAVIER

ALEGRE SANCHO, JUAN J.

SPANISH SCLERODERMA GROUP

FERNÁNDEZ GUTIÉRREZ, BENJAMÍN

BALSA, ALEJANDRO

ORTIZ, ANA M.

SANTANIELLO, ALESSANDRO

BELLOCCHI, CHIARA

LUNARDI, CLAUDIO

MORONCINI, GIANLUCA