Type 1A diabetes, formerly termed insulin-dependent diabetes mellitus (IDDM) is a genetically complex disorder resulting from immune-mediated destruction of the insulin-secreting beta cells. The disease is characterized by the presence of islet autoantibodies (eg, anti-insulin, glutamic acid decarboxylase, and ICA512 (IA-2) autoantibodies) that typically precede the development of diabetes. Several prospective studies have reported that these autoantibodies can appear early in childhood and the presence of two or more of these autoantibodies is highly predictive for the development of diabetes (1, 2). The Diabetes Autoimmunity Study in the Young (DAISY) 3 investigates early genetic and environmental factors contributing to risk of beta cell autoimmunity and progression to diabetes in relatives (siblings and offspring cohort (SOCs)) of patients with type 1A diabetes and a general population newborn cohort (NEC). Children with HLA-DR and DQ genotypes associated with diabetes risk are followed from birth for the development of islet autoantibodies. Genetic susceptibility for development of type 1A diabetes is associated with over 15 genetic loci, with the best characterized loci within the human leukocyte antigen (HLA) region on chromosome 6p21. Common alleles of class II HLA genes, in particular DQ and DR genes, are strongly associated with diabetes risk. To date, the highest risk genotype for development of type 1A diabetes is DQA1* 0501, DQB1* 0201 (DR3) with DQA1* 0301, DQB1* 0302 (DR4), which occurs in approximately 35–50% of new onset type 1A diabetics compared to a population frequency of 2.4%. A number of studies suggest that other genes within the HLA region might influence diabetes susceptibility but the extensive linkage disequilibrium within the region makes the identification of these genes problematic. Recently, several reports in both humans and animal models of type 1A diabetes have suggested that alleles of class I genes (eg, HLA-A) may contribute to diabetes risk and the age of diabetes development (3–6).