A combined large-scale meta-analysis identifies COG6 as a novel shared risk locus for rheumatoid arthritis and systemic lupus erythematosus.
Ann Rheum Dis
; 76(1): 286-294, 2017 Jan.
Article
in En
| MEDLINE
| ID: mdl-27193031
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 top-associated polymorphisms in the discovery phase were selected for replication in additional datasets comprising 13â 641 RA cases and 31â 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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Arthritis, Rheumatoid
/
Adaptor Proteins, Vesicular Transport
/
Lupus Erythematosus, Systemic
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limits:
Humans
Language:
En
Year:
2017
Type:
Article