The generation of self-reactive auto-antibodies is a characteristic feature of autoimmune disease. To prevent this, B-cells expressing self-reactive antibody are removed prior to maturation to antibody secreting plasma cells. Here we show SNPs at 12q13.2, a locus showing reproducible association with multiple autoimmune diseases including type I diabetes (T1D)25-28 regulate the expression of genes implicated in cell-cycle control in trans in B-cells only. Previous studies have demonstrated rs11171739 at 12q13.2 forms a cis-eQTL involving RPS26 in liver8, LCLs15 and leukocytes11. Differential RPS26 expression however appears unable to explain susceptibility to T1D at this locus29 and the causal genes are unresolved. We find a highly significant trans-eQTL in B-cells with IP6K2 (encoding inositol hexakisphosphate kinase-2) (pB-cell=5.8×10−15) (Figure 4a). IP6K2 is required for p53-mediated apoptosis30 and is able to regulate the accumulation of p21/CIP1, a protein involved in cell division, apoptosis of pathogenic memory B-cells31 and is a known susceptibility gene for SLE32. Intriguingly, a further trans-association was found for a transcript mapping 5′ to the actual gene encoding p21/CIP1 (CDKN1A) (pB-cell=2×10−52, pmonocyte=1.8×10−4). This region is denoted as the pseudogene LAP3P2 but
