Fig 1: Identification of causal variants. a We evaluated eight variants located in regulatory regions of ELL2 (Fig. 2c and Supplementary Table 1) using luciferase assays in RPMI-8226, OPM2, and L363 plasmocytoma lines, and in K562 and MOLM-13 cells that represent other hematologic lineages. Consistent with the effect on ELL2 expression in plasma cells but not in peripheral blood, three risk variants (rs3777189-C, rs3777185-C, and rs4563648-G) yielded reduced activity in the plasma cell lines but not in the control cell lines, whereas the remaining variants showed opposite or inconsistent effects. Plotted values represent log2-ratios of luciferase activities for the risk alleles over their corresponding protective alleles (median over tri or quadruplicates). b To identify the responsible transcription factors, we carried out sequence analyses and electrophoretic mobility shift assays (EMSA) (Supplementary Figs. 5 and 6). Shown here is EMSA with nuclear extract (NE) from OPM2 cells (lanes 2–4 and 6–8), and probes representing genomic sequence at rs3777189 with the risk/low-expressing allele (C) or the protective/high-expressing allele (G) in the center (lanes 1–4 and 5–8, respectively). The G allele showed an allele-specific shift (lane 6) that was outcompeted with unlabeled probe (ULP; lane 7) and supershifted with MAFF/G/K antibody (lane 8). Similar results were seen with L363 cells (Supplementary Fig. 5). c Sequence analysis predicted loss of a MAFF/G/K motif (Supplementary Table 4). Shown here is the MAFK motif from the HOCOMOCO-10 database. Arrow indicates G changed to C by the rs3777189-C risk variant