AbstractIL2RAis associated with multiple autoimmune diseases including type 1 diabetes (T1D). Higher expression ofIL2RAmRNA and its protein product CD25 in T lymphocytes is associated with a T1D-protective haplotype. Here we show that a rare variation of this haplotype that loses the protective allele at a single SNP, rs61839660, reducesIL2RAexpression and T1D protection, identifying it as the causal factor in disease.