In order to model the effect of PTPN22 on rheumatoid arthritis (RA), we determined the combination of single-nucleotide-polymorphisms (SNPs) showing the strongest association with RA. Three SNPs (rs2476601-rs12730735-rs11102685) were selected for which we estimated the genotypic relative risks (GRRs) of the corresponding genotypes. On the basis of these GRRs we defined four at-risk genotypic classes. Relative to the class of reference risk, individuals had a risk approximately multiplied by two, three, or four. This classification was confirmed by the excess of identity-by-descent (IBD) sharing (IBD = 2) for the sibs of an index in the high-risk class and by excess of non-IBD sharing (IBD = 0) when the index belonged to the low-risk class. The observed data could not be explained by the role of a single variant but were compatible either with a joint effect of the three typed SNPs of PTPN22 on RA or with the role of two untyped variants.