Background There is strong evidence that Rheumatoid Arthritis (RA) patients expressing anti-cyclic citrullinated peptide antibodies (ACPA) have a differential genetic background compared to ACPA-negative RA patients.
Objectives We performed a genome-wide association study (GWAS) on ACPA-positive RA patients to identify additional disease susceptibility genes.
Methods A total of 924 ACPA-positive RA patients and 1,524 healthy controls were genotyped in 582,591 single-nucleotide polymorphisms (SNPs) in the discovery phase. The most significant SNPs were then analyzed in an independent cohort of 863 ACPA-positive patients and 1,152 healthy controls.
Results In the discovery phase we found suggestive association (P <5e-4) for 60 novel loci with the risk to develop ACPA-positive RA. In the validation phase, we nominally replicated the association of 12 candidate loci (P<0.05 same direction of effect as in GWAS). Combining the data from the discovery and validation cohorts we found a genome-wide significant association between an intronic SNP in Solute Carrier family 8 gene (SLC8A3) and the risk to develop ACPA-positive RA (OR (95%CI): 1.42 (1.25-1.6), combined P=3.19e-8).
Conclusions This study identified a new locus associated with ACPA-positive RA. These results support the evidence that RA patients positive for ACPA have a specific genetic background.
Disclosure of Interest None declared