Our scan found associations with SNPs within the chromosome 10p15 region containing CD25, encoding the high-affinity receptor for IL-2. This is consistent with a previous report of associations of this region with T1D91. The CD25 region has previously been shown to be associated with Graves’ disease98 and the present study also provides evidence of association with RA (combined trend test P=5×10-8, P=~7×10-6 for RA and T1D separately, Supplementary Table 11). This finding has clear biological connections to the evidence of association between T1D and a region of 4q27 revealed by the multilocus analysis (Supplementary Table 12, Supplementary Fig. 12). This region contains the genes encoding both IL-2 and IL-21. Together with studies in the NOD (nonobese diabetic) mouse model of T1D, which have shown that a major non-MHS locus (Idd3) reflects regulatory variation of the Il2 gene99, our results point to the primary importance of the IL-2 pathway in T1D and other autoimmune diseases.
