Even the strongest genetic risk factor for RA, the variants in the HLA-DRB1 gene suggested by the shared epitope (SE) hypothesis [2], confer only a moderate risk increase for RA, with an odds ratio (OR) of 4–6 in European Caucasians with regard to anti-citrullinated protein antibodies (ACPA) positive RA [3], [4]. The gene discussed is HLA-DRB1; the disease is rheumatoid arthritis.