Recent results from genetic and treatment studies have shed new light on chronic 
inflammatory and autoimmune diseases such as rheumatoid arthritis (RA). In 
particular, genome-wide association studies (GWAS) have provided supportive 
evidence that RA is a disease with a strong genetic background. Interestingly, a 
series of candidate genes have been identified outside of the classical major 
histocompatibility (MHC) locus, which had long been regarded as the major 
contributor to the pathogenesis of this disease. Among these genes, PTPN22 plays 
an outstanding role. CD40, STAT4, PRM1, and TNFAIP3 also seem to be of 
relevance. Interestingly, there is a significant overlap between RA 
susceptibility genes and those of other autoimmune diseases such as systemic 
lupus erythematosus (SLE) and type 1 diabetes, which suggests common pathogenic 
mechanisms. Genetic analyses may not only provide new insights into the 
pathogenesis of RA, but may also open new avenues for therapeutic approaches, 
because overactive immune-signaling pathways might specifically be addressed by 
biologic therapies. However, the predictive value of many of the recent findings 
of large-scale genetic analyses in identifying new genetic polymorphisms remains 
low. We describe the current knowledge about the role of non-MHC genes in the 
pathogenesis of rheumatoid arthritis.