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Abstract: Objectives During the last years, genome-wide
association studies (GWASs) have identified a number of
common genetic risk factors for rheumatoid arthritis (RA)
and systemic lupus erythematosus (SLE). However, the
genetic overlap between these two immune-mediated
diseases has not been thoroughly examined so far. The
aim of the present study was to identify additional risk
loci shared between RA and SLE.
Methods We performed a large-scale meta-analysis of
GWAS data from RA (3911 cases and 4083 controls)
and SLE (2237 cases and 6315 controls). The topassociated
polymorphisms in the discovery phase were
selected for replication in additional datasets comprising
13 641 RA cases and 31 921 controls and 1957
patients with SLE and 4588 controls.
Results The rs9603612 genetic variant, located nearby
the COG6 gene, an established susceptibility locus for
RA, reached genome-wide significance in the combined
analysis including both discovery and replication sets (p
value=2.95E?13). In silico expression quantitative trait
locus analysis revealed that the associated polymorphism
acts as a regulatory variant influencing COG6 expression.
Moreover, protein?protein interaction and gene ontology
enrichment analyses suggested the existence of overlap
with specific biological processes, specially the type I
interferon signalling pathway. Finally, genetic correlation
and polygenic risk score analyses showed crossphenotype
associations between RA and SLE.
Conclusions In conclusion, we have identified a new
risk locus shared between RA and SLE through a metaanalysis
including GWAS datasets of both diseases. This
study represents the first comprehensive large-scale
analysis on the genetic overlap between these two
Fuente: Ann Rheum Dis 2017;76:286-294
Editorial: BMJ Publishing Group
Año de publicación: 2017
Nº de páginas: 10
Tipo de publicación: Artículo de Revista
VIDAL BRALO, LAURA
RODRÍGUEZ RODRÍGUEZ, LUIS
MIGUEL ANGEL GONZALEZ-GAY MANTECON
GONZÁLEZ ÁLVARO, ISIDORO
ORTEGO CENTENO, NORBERTO
AYALA GUTIÉRREZ, MARÍA M.
GARCÍA HERNÁNDEZ, FRANCISCO JOSÉ
GONZÁLEZ ESCRIBANO, M. FRANCISCA
SABIO, JOSÉ MARIO
ALARCÓN RIQUELME, MARTA E.