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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
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 of
common risk loci.
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
Consultar en UCrea Leer publicación
LÓPEZ ISAC, ELENA
MARTÍN, JOSE EZEQUIEL
SIMEÓN, CARMEN P.
ORTEGO CENTENO, NORBERTO
ALEGRE SANCHO, JUAN J.
FERNÁNDEZ GUTIÉRREZ, BENJAMÍN
ORTIZ, ANA M.
MIGUEL ANGEL GONZALEZ-GAY MANTECON