RT Journal Article
T1 A combined large-scale meta-analysis identifies COG6 as a novel shared risk locus for rheumatoid arthritis and systemic lupus erythematosus.
A1 Marquez, Ana
A1 Vidal-Bralo, Laura
A1 Rodriguez-Rodriguez, Luis
A1 Gonzalez-Gay, Miguel A
A1 Balsa, Alejandro
A1 Gonzalez-Alvaro, Isidoro
A1 Carreira, Patricia
A1 Ortego-Centeno, Norberto
A1 Ayala-Gutierrez, Maria M
A1 Garcia-Hernandez, Francisco Jose
A1 Gonzalez-Escribano, M Francisca
A1 Sabio, Jose Mario
A1 Tolosa, Carles
A1 Suarez, Ana
A1 Gonzalez, Antonio
A1 Padyukov, Leonid
A1 Worthington, Jane
A1 Vyse, Timothy
A1 Alarcon-Riquelme, Marta E
A1 Martin, Javier
K1 Gene Polymorphism
K1 Rheumatoid Arthritis
K1 Systemic Lupus Erythematosus
AB 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. 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 top-associated 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. 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 cross-phenotype associations between RA and SLE. In conclusion, we have identified a new risk locus shared between RA and SLE through a meta-analysis including GWAS datasets of both diseases. This study represents the first comprehensive large-scale analysis on the genetic overlap between these two complex disorders.
PB Elsevier
YR 2016
FD 2016-05-18
LK http://hdl.handle.net/10668/10097
UL http://hdl.handle.net/10668/10097
LA en
NO Márquez A, Vidal-Bralo L, Rodríguez-Rodríguez L, González-Gay MA, Balsa A, González-Álvaro I, Carreira P, et al. A combined large-scale meta-analysis identifies COG6 as a novel shared risk locus for rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis. 2017 Jan;76(1):286-294
NO This work was supported by the following grants: SAF2012-34435 from the Spanish Ministry of Economy and Competitiveness, P12-BIO-1395 from Consejería de Innovación, Ciencia y Tecnología, Junta de Andalucía (Spain), the European IMI BTCure Program, the EU/EFPIA Innovative Medicines Initiative Joint Undertaking PRECISESADS (ref: 115565), the Cooperative Research Thematic Network (RETICS) programme, RD12/0009/0004 (RIER), from Instituto de Salud Carlos III (ISCIII, Health Ministry, Madrid, Spain) and PI12/02558 from Instituto de Salud Carlos III (ISCIII, Health Ministry, Madrid, Spain). AM is recipient of a Rio Hortega fellowship (CM13/00314) from the Ministry of Economy and Competitiveness through the Instituto de Salud Carlos III (ISCIII, Health Ministry, Madrid, Spain).
DS RISalud
RD Apr 7, 2025