Table 1.
Implicated target genes at 46 BMD GWAS loci in hMSC-derived osteoblasts
| GWAS Locus | Sentinel SNP | Proxy SNP (r2) | Implicated genes (FPKM) | GWAS Set |
|---|---|---|---|---|
| ANKFN1 | rs72829754 | rs56335503 (0.96), rs8065311 (0.95) | NOG (21.00) | Heel |
| C11orf58 | rs56928337 | rs78152188 (0.99) | TCONS_00019584 (NA), TCONS_00019858 (NA) | Heel |
| CCND1 | rs4980659 | rs6606645 (0.91) | CCND1 (88.53) | DEXA |
| CRADD | rs7969076 | rs7953280 (0.88) | SOCS2 (3.78), SOCS2-AS1 (0.59) | Heel |
| DLX5 | rs1724298 | rs1724298 (1) | SHFM1 (9.38) | Heel |
| DLX6-AS1 | rs17598132 | rs73402679 (0.94) | SHFM1 (9.38) | Heel |
| DNM3 | rs12041600 | rs1992549 (1), rs1992550 (1), rs2586393 (0.99), rs6694387 (0.94) | DNM3OS (8.92), MIR199A2 (NA) | Heel |
| EMP1 | rs76243438 | rs116942315 (1), rs117604090 (1), rs199595633 (1), rs75180224 (1) | EMP1 (30.57) | Heel |
| EN1 | rs62159864 | rs62159869 (0.97) | TCONS_00004419 (NA) | Heel |
| EPDR1 | rs1717731 | rs939666 (0.87) | EPDR1 (25.59), SFRP4 (0.88) | Heel |
| FADS2 | rs174574 | rs3834458 (0.92) | FADS1 (19.09) | Heel |
| FRZB | rs10206992 | rs36090522 (0.99), rs9288087 (0.99) | FRZB (12.92) | Heel |
| GMDS-AS1 | rs4959677 | rs1010762 (0.85) | LINC01600 (NA), TCONS_00011252 (NA) | Heel |
| GNG12-AS1 | rs143243230 | rs143243230 (1) | WLS (12.78) | Heel |
| HOXA-AS3 | rs62454420 | rs62454420 (1) | CBX3 (15.70), SKAP2 (5.32) | Heel |
| HOXA11 | rs17501090 | rs149457254 (0.82) | HIBADH (10.12), TAX1BP1 (9.35) | Heel |
| HOXC6 | rs736825 | rs765634 (0.88) | HOXC-AS1 (0.34), HOXC4 (0.15), HOXC5 (0.36), HOXC9 (8.71), SMUG1 (5.16), TCONS_00020435 (0.02), TCONS_00020436 (NA), TCONS_00020437 (0.01), TCONS_00020438 (NA) | DEXA |
| IGFBP7 | rs11133474 | rs11133472 (0.99), rs11133474 (1) | IGFBP7 (1445.99), IGFBP7-AS1 (0.58) | Heel |
| JAG1 | rs17457340 | rs141094380 (0.95), rs78438678 (0.95) | LOC339593 (NA), TCONS_l2_00016479 (NA), TCONS_l2_00016480 (NA), TCONS_l2_00016851 (0.01) | Heel |
| KCNE2 | rs55787537 | rs55787537 (1) | LINC00649 (0.02), TCONS_00029004 (NA) | Heel |
| KIAA2012 | rs62195575 | rs13000317 (0.82), rs13384015 (0.87) | CDK15 (0.09), KIAA2012 (NA) | Heel |
| KIAA2018 | rs1026364 | rs150722690 (0.90), rs150722690 (0.86), rs16861312 (0.90), rs9288983 (0.90), rs9851731 (0.87) | ATP6V1A (21.00), NAA50 (13.11) | DEXA |
| LEKR1 | rs344081 | rs344088 (0.97) | SSR3 (60.86), TIPARP (11.64), TIPARP-AS1 (0.15) | DEXA |
| LINC00880 | rs56082403 | rs13322435 (0.98), rs56406311 (0.9), rs9817452 (0.9), rs9854955 (0.98) | LEKR1 (0.08), LINC00886 (0.55), SSR3 (60.86), TCONS_00006285 (NA), TCONS_l2_00019596 (0.03), TIPARP (11.64), TIPARP-AS1 (0.15) | Heel |
| LOC101929268 | rs6471752 | rs72639005 (0.84), rs55864946 (0.84), rs72639011 (0.84), rs72639012 (0.84) | LOC101929217 (NA), SNAI2 (39.39), TCONS_00014692 (0.01) | Heel |
| MAPT/WNT3 | rs1864325 | 17:44121917:C:T (0.99), 17:44231617:A:T (0.99), 17:44237372:G:C (0.99), 17:44245359:G:A (0.84), rs62063683 (0.99), rs974291 (0.99), rs974292 (0.99) | KANSL1 (1.89), KANSL1-AS1 (0.71) | DEXA |
| MED13L | rs73200209 | rs17498543 (0.84) | MIR4472–2 (NA) | DEXA |
| MEPE | rs6532023 | rs1471401 (1) | SPP1 (12.86) | Both |
| MLPH | rs58057291 | rs13408361 (0.9), rs6722471 (0.93), rs7569197 (0.9), rs7571898 (0.9), rs7598954 (0.87), rs9287620 (0.87) | COL6A3 (125.76), TCONS_00003518 (NA) | Heel |
| MTAP | rs7035284 | rs7852691 (0.98) | MIR31HG (9.48) | DEXA |
| PHLDB1 | rs10790255 | rs10892247 (0.85) | PHLDB1 (11.37) | Heel |
| PLEKHG4 | rs17680862 | rs8047360 (0.8), rs8050375 (0.8), rs114485334 (0.83) | B3GNT9 (27.79), CES4A (0.22), FBXL8 (2.05), TRADD (11.46) | Heel |
| RERE | rs2252865 | rs2708633 (0.92), rs301789 (0.93), rs301790 (0.93), rs301791 (0.93), rs301792 (0.93) | LOC102724552 (NA), RERE (0.94) | DEXA |
| RNU5F-1 | rs2275707 | rs1694593 (0.96), rs1694594 (0.96) | SLC30A10 (0.00) | Heel |
| SFRP4 | rs17236800 | rs10264106 (1), rs1014939 (0.99), rs2167269 (0.99) | STARD3NL (6.44), TRG-AS1 (NA) | Both |
| SLC1A3 | rs1428968 | rs1428968 (1) | SLC1A3 (0.78) | Heel |
| SLC8A1 | rs10490046 | rs10490046 (1) | SLC8A1 (3.39) | Both |
| SLX4IP | rs6040006 | rs111539884 (0.88), rs74516716 (0.88), rs78532542 (0.88) | LOC339593 (NA), TCONS_l2_00016479 (NA), TCONS_l2_00016480 (NA), TCONS_l2_00016851 (0.01) | Heel |
| SMAD3 | rs1545161 | rs1545161 (1), rs28587205 (0.98), rs72219900 (0.99) | SMAD3 (2.59) | Both |
| SMAD9 | rs556429 | rs17217404 (0.95) | SMAD9 (11.59) | DEXA |
| SMG6 | rs35401268 | rs35401268 (1) | SMG6 (3.19) | Both |
| SPEN | rs6701290 | rs6688051 (0.93) | FLJ37453 (NA), SPEN (1.15), ZBTB17 (6.09) | Heel |
| SPTB | rs1957429 | rs28370916 (0.83) | SPTB (0.02) | DEXA |
| STARD3NL | rs6956946 | rs1524068 (1), rs940347 (1) | EPDR1 (25.59), SFRP4 (0.88) | Both |
| TBPL2 | rs34652660 | rs12431542 (0.90), rs202007979 (0.89), rs4901570 (0.90), rs8009706 (0.90) | KTN1 (10.46), KTN1-AS1 (0.03) | DEXA |
| WLS | rs17482952 | rs17482952 (1), rs79441491 (0.97) | WLS (12.78) | DEXA |
For each locus, proxy SNPs in open chromatin looping to an open promoter are reported, together with their sentinel SNPs and the associated GWAS loci. Looping interactions and open chromatin maps were derived from promoter-focused Capture C and ATAC-seq experiments on hMSC-derived osteoblasts cultures from 3 or more individuals. Average expressions (in FPKM) of the target genes in hMSC-derived osteoblasts from RNA-seq experiments from the same 3 individuals are also reported.