Recently, we devised an analytical approach to fine map risk of the variants in the MHC region by imputing genotypes of amino acid polymorphisms in the classical HLA genes and classical two- and four-digit alleles.24–26 Each classical four-digit HLA allele corresponds to a unique amino acid sequence encoded by the HLA gene, and thus polymorphic residues at each amino acid position could also be targets of disease-risk association studies. This approach has been used for successfully fine mapping HLA alleles of several autoimmune or immune-mediated diseases, including durable host control of HIV infection (MIM 609423), seropositive and seronegative rheumatoid arthritis (MIM 180300), myasthenia gravis (MIM 254200), and follicular lymphoma (MIM 613024).25–29 In certain instances, our approach has been able to pinpoint individual amino acid sites that might account for disease risk within HLA molecules.25–27