Recent advances in the genetics of rheumatoid arthritis

To review the recently discovered genetic risk loci in rheumatoid arthritis (RA), the pathways they implicate, and the genetic architecture of RA.

Since 2008 investigators have identified many common genetic variants that confer disease risk through single nucleotide polymorphism genotyping studies; the list of variants will no doubt continue to expand at a rapid rate as genotyping technologies evolve and case-control sample collections continue to grow. In aggregate, these variants implicate pathways leading to NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation, the interluekin-2 signaling pathway, and T-cell activation.

Although the effect of any individual variant is modest and even in aggregate considerably less than that of the major histocompatability complex, discovery of recent risk variants suggests immunological processes that are involved in disease pathogenesis.