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A combined large-scale meta-analysis identifies COG6 as a novel shared risk locus for rheumatoid arthritis and systemic lupus erythematosus

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 (pvalue=2.95E?13). In silico expression quantitative trait locus analysis revealed that the associated polymorphismacts 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 Iinterferon 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 complex disorders.

 Fuente: Annals of the Rheumatic Diseases, 2017, 76(1), 286-294

 Editorial: BMJ Publishing Group

 Año de publicación: 2017

 Nº de páginas: 10

 Tipo de publicación: Artículo de Revista

 DOI: 10.1136/annrheumdis-2016-209436

 ISSN: 0003-4967,1468-2060

Authorship

MÁRQUEZ, ANA

VIDAL BRALO, LAURA

RODRÍGUEZ RODRÍGUEZ, LUIS

BALSA, ALEJANDRO

GONZÁLEZ ÁLVARO, ISIDORO

CARREIRA, PATRICIA

ORTEGO CENTENO, NORBERTO

AYALA GUTIÉRREZ, MARÍA M.

GARCÍA HERNÁNDEZ, FRANCISCO JOSÉ

GONZÁLEZ ESCRIBANO, M. FRANCISCA

SABIO, JOSÉ MARIO

TOLOSA, CARLES

SUÁREZ, ANA

GONZÁLEZ, ANTONIO

PADYUKOV, LEONID

WORTHINGTON, JANE

VYSE, TIMOTHY

ALARCÓN RIQUELME, MARTA E.

MARTÍN, JAVIER