There is a dose effect of shared epitope positive HLA-DRB1 alleles on the risk to develop RA: subjects with two shared epitope positive HLA-DRB1 alleles are at higher risk than those with one shared epitope positive HLA-DRB1 allele, and subjects with no shared epitope positive HLA-DRB1 allele are at the lowest risk. The gene discussed is HLA-DRB1; the disease is rheumatoid arthritis.