The HLA-B*3906 allele imparts a high risk of diabetes only on specific HLA-DR/DQ haplotypes

AIMS/HYPOTHESIS: We investigated the risk associated with HLA-B*39 alleles in the context of specific HLA-DR/DQ haplotypes. METHODS: We studied a readily available dataset from the Type 1 Diabetes Genetics Consortium that consists of 2,300 affected sibling pair families genotyped for both HLA alleles and 2,837 single nucleotide polymorphisms across the major histocompatibility complex region. RESULTS: The B*3906 allele significantly enhanced the risk of type 1 diabetes when present on specific HLA-DR/DQ haplotypes (DRB1*0801-DQB1*0402: p = 1.6 × 10(−6), OR 25.4; DRB1*0101-DQB1*0501: p = 4.9 × 10(−5), OR 10.3) but did not enhance the risk of DRB1*0401-DQB1*0302 haplotypes. In addition, the B*3901 allele enhanced risk on the DRB1*1601-DQB1*0502 haplotype (p = 3.7 × 10(−3), OR 7.2). CONCLUSIONS/INTERPRETATION: These associations indicate that the B*39 alleles significantly increase risk when present on specific HLA-DR/DQ haplotypes, and HLA-B typing in concert with specific HLA-DR/DQ genotypes should facilitate genetic prediction of type 1 diabetes, particularly in a research setting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-011-2161-1) contains supplementary material, which is available to authorised users.