Table 1. MCF-7 BCa Risk Enhancers.
Listed are the 10 best BCa risk loci in MCF-7 and the corresponding 10 MCF-7 risk enhancers which are most suitable for follow up testing. Each enhancer overlaps the most significant GWAS SNP at the locus, and the locus shows both an enrichment greater than 2 (frequency of BCa credible risk variants (CRVs) overlapping enhancers compared to background overlap frequency), as well as a proportion of the CRV risk span that overlaps enhancers greater than more than 95% background overlap proportions. The enrichment and overlap values may be modified by overlap of risk SNPs with other enhancers at the same locus. The overall GWAS significance, ER+ GWAS significance, and reported genes from Michailidou et. al. are listed. Additionally, all but the enhancer at locus 19 are unique to MCF-7 and do not overlap HMEC enhancers locations, so the differentially expressed genes (relative to HMEC) within 500 Kb or 1 MB of each lead SNP are identified as putative risk genes in MCF-7.
| Locus | Alt. Locus ID | CRVs Enh. Overlap | CRVs in Locus | Hyper. P.Val. (−log) | Ratio Enrich. | Span Overlap Signif. (−log) | Lead SNP ID | Comb. GWAS P.Val. | Comb. GWAS P. Val., ER | Risk Enhancer Start | Risk Enhancer Stop | Gene | MCF-7 DE Genes 0–500Kb | MCF-7 DE Genes 500Kb −1Mb |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1p36.22 | 1_10566215 | 8 | 50 | 4.29 | 5.79 | 1.72 | rs2506889 | 2.38E-20 | 1.10E-07 | 10595877 | 10599012 | PEX14 | APITD1, TARDBP, UBE4B, PEX14 | SRM, SLC25A33, PIK3CD, LZIC, PTCHD2, CLSTN1, EXOSC10, MTOR |
| 3p26.1 | 3_4742276 | 1 | 22 | 0.65 | 3.31 | 1.71 | rs6787391 | 9.07E-19 | 1.20E-15 | 4727872 | 4732087 | EGOT, ITPR1 | BHLHE40, ARL8B, ITPR1, | EDEM1 |
| 6q25 | 6_151952332 | 10 | 10 | 12.50 | 17.64 | 2.19 | rs60954078 | 2.84E-54 | 1.70E-22 | 151948050 | 151959756 | ESR1 | ZBTB2, RMND1, AKAP12, C6orf211, SYNE1, ESR1 | MTHFD1L, PLEKHG1 |
| 8q22.3 | 8_102478959 | 2 | 8 | 1.50 | 6.62 | 1.66 | rs514192 | 5.61E-09 | 9.90E-09 | 102478133 | 102481107 | YWHAZ, GRHL2, KLF10 | ZNF706, GRHL2 | ANKRD46, YWHAZ, RRM2B, UBR5, PABPC1 |
| 10p14 | 10_9088113 | 30 | 42 | 23.50 | 8.93 | 2.15 | rs60954078 | 1.73E-10 | 6.00E-08 | 9074392 | 9089320 | GATA3 | NA | GATA3 |
| 12q24.31 | 12_120832146 | 2 | 26 | 0.80 | 2.32 | 1.54 | rs206966 | 3.79E-08 | 1.40E-06 | 120831824 | 120833249 | DYNLL1, GATC | TRIAP1, SRSF9, POP5, PXN, MSI1, DYNLL1, COQ5, UNC119B, CCDC64, RNF10 | PRKAB1, P2RX4, CIT, ANAPC5 |
| 16q23.2 | 16_80650805 | 8 | 17 | 9.69 | 26.12 | 2.66 | rs7500067 | 4.06E-27 | 2.90E-21 | 80647147 | 80651103 | CDYL2 | ATMIN, CENPN, CDYL2 | GAN, CMIP |
| 17q25.3 | 17_77781725 | 3 | 13 | 2.56 | 9.98 | 1.90 | rs8082452 | 1.14E-10 | 2.40E-06 | 77769769 | 77772332 | NA | CBX2, CBX8, CBX4, CARD14, SGSH, SLC26A11, TBC1D16, EIF4A3 | TIMP2, LGALS3BP, ENDOV, USP36, RPTOR |
| 19pl3.12 | 19_13954571 | 19 | 43 | 13.35 | 8.74 | 2.74 | rs2594714 | 1.08E-08 | 1.70E-05 | 13948902 | 13955856 | JUNB, NANOS3 | MIR24–2, PALM3, SAMD1, CCDC130, ZSWIM4, C19orf57, PODNL1, ASF1B, | CALR, SYCE2, TRMT1, CD97, GIPC1, DNAJB1, HOOK2, MAST1, |
| 21q21.1 | 21_16520832 | 2 | 2 | 4.32 | 143.22 | 2.52 | rs2403907 | 1.87E-32 | 4.20E-23 | 16570278 | 16574820 | NRIP1 | NRIP1 | HSPA13, USP25 |