Fig. 2

Functional analysis of the 1p36.33 risk locus. a The set of most likely functional variants at 1p36.33 and their P value rank (1–10, in red) is shown as well as overlapping RefSeq genes on chr1: 885,555-904,522 (NCBI GRCh37/Hg19). ENCODE data for histone modification marks (H3K4me1, H3K4me3, H3K27Ac) are indicated by colored density plots. Open chromatin (DNase hypersensitivity regions, DNase clusters) and binding of transcription factors (TF ChIP) are indicated by horizontal bars. The numbers next to each bar indicate the number of cell lines with DNase clusters, or the number of different transcription factors bound across all tested cell lines. The panel is adapted from the UCSC Genome Browser. b Expression QTLs in histologically normal autopsy-derived pancreatic tissues (n = 149) from the GTEx consortium (GTEx), the Laboratory of Translational Genomics histologically normal adjacent-to-tumor pancreatic tissue set (LTG, n = 95), and the TCGA pancreatic cancer tissue set (TCGA/PAAD, n = 115). Normalized NOC2L expression is shown on the y axis and genotypes at the marker SNP at 1p36.33 on the x axis. Risk-increasing alleles are marked in red. Note that no samples in the LTG and TCGA/PAAD sets were of the minor homozygous risk genotype (GG). The box-and-whisker plots show the median (horizontal middle line within each box), interquartile range (top and bottom horizontal lines of each box), and 1.5 times the IQR (whiskers). c Analysis of the effects of 1p36.33 variants on transcription factor motifs for rs13303160 (r² = 0.93 with rs13303010 in 1000 G EUR). The risk allele (C) at this marker alters predicted DNA-binding motifs for SMARCC1 and AP-1 proteins