Advances in the genetics of rheumatoid arthritis point to subclassification into distinct disease subsets

In the past few years considerable advances have been made in the genetics of susceptibility to rheumatoid arthritis (RA). For decades the HLA-DRB1 alleles were the only extensively replicated genetic factor, but more genetic risk factors have now been identified that predispose to RA. Interestingly, several of the observed genetic variants conferred risk to anticitrulline-peptide antibody (ACPA)-positive RA and two variants may be restricted to ACPA-negative RA, pointing to the need for subclassification of RA. The current manuscript reviews recently identified genetic factors predisposing to ACPA-positive RA and ACPA-negative RA. Additionally, although being scarcely explored, genetic variants affecting the severity of disease course are discussed.