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

作者：Marquez Ana^*; Vidal Bralo Laura; Rodriguez Rodriguez Luis; Gonzalez Gay Miguel A; Balsa Alejandro; Gonzalez Alvaro Isidoro; Carreira Patricia; Ortego Centeno Norberto; Ayala Gutierrez Maria M; Jose Garcia Hernandez Francisco; Francisca Gonzalez Escribano M; Mario Sabio Jose; Tolosa Caries; Suarez Ana; Gonzalez Antonio; Padyukov Leonid; Worthington Jane; Vyse Timothy; Alarcon Riquelme Marta E; Martin Javier

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

DOI：10.1136/annrheumdis-2016-209436

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 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.
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 cross-phenotype associations between RA and SLE.
Conclusions 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.

• 出版日期2017-1