Where do we stand with the genetics of psoriatic arthritis?

Psoriasis and psoriatic arthritis (PsA) are interrelated heritable diseases. Polymorphisms in the genes encoded in the major histocompatibility complex region have consistently been associated with psoriasis and PsA and account for about 30% of the genetic risk. Recently, the results of multiple well-powered genome-wide association studies have identified several additional loci outside the major histocompatibility complex region associated with psoriasis risk, including three genes involved in interleukin (IL)-23 signaling (IL-23R, IL-23A, IL-12B), two genes that regulate nuclear factor-kappaB signaling (TNIP1, TNFAIP3), and two genes involved in the modulation of T-helper type 2 immune responses (IL-4, IL-13). These initial findings are beginning to illuminate the molecular pathways implicated in the pathogenesis of psoriasis and suggest priority targets for study in PsA cohorts. Of course, the next step will be to identify genetic risk factors specifically associated with PsA, and indeed, a formal genome-wide association study on PsA is being undertaken.