Fig. 2: Functional annotations and prioritization of associated SNPs at 3p26.1 region.

a Regional plot of association signals in the combined stages and annotations with ovary-specific epigenomics data, including DNase-Seq, H3K27ac, and H3K4me1 histone modification ChIP-seq profiles for primary ovary tissue (data from Roadmap), and ATAC-seq profiles from three ovarian cancer cell lines (OVCA432, DOV13, and SKOV3). The region of rs9311399 overlaps with peaks of H3K27ac, H3K4me1, and DNase I hypersensitivity sites (DHSs) measured by DNase-Seq and ATAC-seq in ovary tissues/cells. b TF footprint analysis using ATAC-seq. Footprint analysis showed that the rs9311399 associated sequences could affect the TF footprint. The average profiles estimated by Sasquatch software showed the highest-scoring k-mer pair (blue = reference, red = variant). The k-mers were two sequences showing the biggest difference of protein footprint with and without the investigated variant. The number represented times that k-mer within open chromatin sites (indicated by #). c Luciferase reporter assay using vectors containing rs9311399 in OVCA432 cells. Luciferase signals were normalized to Renilla signals (n = 3). Luciferase reporter assay showed the effect allele A fragment had a higher activity, compared with the non-effect allele C fragment. d EMSA assay showed rs9311399-A caused enhanced protein binding relative to rs9311399-C using synthetic allele-specific probes and nuclear extracts from SKOV3 cells. The rs9311399-C allele was associated with a reduction of 20% in the intensity of the shifted protein band compared to the A allele. The competitor was the unlabeled probe with the corresponding genotype. Statistical comparisons of relative luciferase activity were undertaken using Student’s t tests. Data are shown as means ± sd with *P < 0.05, ***P < 0.001.