PRTN3 and rheumatoid arthritis: Second, even though we focused our study on the SNPs within the MHC region and selected CpG sites based on previous work, the success of identifying a CpG site, with methylation that mediates a novel interaction between genotype and smoking in the risk of developing ACPA-positive RA, suggests that this type of epigenetic regulation may be more common than currently acknowledged, and the findings reported here may simply be the “tip of the iceberg”.