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Table 1 Genome-wide significant loci (signals 1–27) and suggestive loci (signals S1-S13) supported by multiple phenotypes or skeletal sites

From: Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual

Signal SNP Phenotype Chr Position A1 A2 AFa Beta SE P r2b Infoc Nearest genef Novelg/ known Suggestive in ALSPACh
1 rs2762826 TBLH BMC a-size 1 52,785,140 C T 0.071 0.425 0.075 1.48 × 10–8   1 ZFYVE9 [P] Novel  
  rs74944906 TBLH BMD a-size 1 52,779,069 G T 0.948 − 0.438 0.089 8.91 × 10–7 1 1    
2 rs13407288 Femoral neck BMD a-size 2 28,611,855 G T 0.805 0.271 0.049 3.76 × 10–8   0.849 FOSL2 Novel  
  rs13407288 Femoral neck BMD b-timing 2 28,611,855 G T 0.805 0.243 0.049 8.08 × 10–7   0.849    
3 rs78996674 Total hip BMC c-velocity 3 71,412,084 T C 0.941 − 0.469 0.082 1.36 × 10–8   0.988 FOXP1 Novel  
4 rs10804749 Femoral neck BMC a-size 3 99,179,665 T G 0.808 − 0.267 0.049 4.57 × 10–8   0.998 MIR548G, Novel  
  rs73138342 Femoral neck BMC c-velocity 3 99,157,560 C T 0.847 − 0.271 0.053 3.43 × 10–7 0.92 0.987 COL8A1 [P]   
  rs4453878 Femoral neck BMD a-size 3 99,170,409 C T 0.819 − 0.251 0.050 6.64 × 10–7 1 0.998    
5 rs4591452 Total hip BMC c-velocity 3 149,208,719 C T 0.893 0.352 0.060 6.73 × 10–9   0.99 TM4SF4 Novel  
  rs72615628 Total hip BMD c-velocity 3 149,210,256 A G 0.893 0.328 0.060 5.29 × 10–8 1 0.99    
6 rs78543504 Total hip BMD b-timing 4 3,699,405 A T 0.911 0.385 0.068 2.29 × 10–8   0.881 ADRA2C Novel  
  rs78543504 Total hip BMD c-velocity 4 3,699,405 A T 0.911 0.385 0.068 2.29 × 10–8   0.881    
  rs4916624 Total hip BMC c-velocity 4 3,691,543 A T 0.927 0.368 0.072 3.84 × 10–7 0.97 0.882    
7 rs202099172 Distal 1/3 radius BMC b-timing 5 28,308,653 ATAT A 0.926 0.420 0.074 1.44 × 10–8   0.865 CDH9 Novel  
  rs202099172 Distal 1/3 radius BMD b-timing 5 28,308,653 ATAT A 0.926 0.348 0.071 9.39 × 10–7   0.865    
8 rs11751016 Distal 1/3 radius BMD c-velocity 6 52,017,180 G A 0.708 − 0.228 0.042 4.76 × 10–8   0.99 MIR133B, IL17A [P] Novel  
9 rs77977968 TBLH BMC c-velocity 7 139,335,659 C T 0.948 0.510 0.088 9.34 × 10–9   0.952 HIPK2 Novel  
10 rs60380629 TBLH BMD c-velocity 7 151,694,110 C T 0.935 0.454 0.078 8.18 × 10–9   0.979 GALNTL5 Novel  
  rs60380629 Total hip BMD b-timing 7 151,694,110 C T 0.935 0.430 0.077 2.64 × 10–8   0.979    
  rs79289671 Total hip BMD c-velocity 7 151,692,941 C T 0.930 0.400 0.075 9.93 × 10–8 0.99 0.97    
11 rs7860141 Spine BMC c-velocity 9 32,137,832 G C 0.816 − 0.282 0.051 4.87 × 10–8   0.999 ACO1 Novel y
12 rs1331428 TBLH BMD c-velocity 9 137,835,202 C T 0.483 − 0.221 0.039 2.49 × 10–8   0.988 FCN1 Novel  
  rs4841948 Total hip BMD c-velocity 9 137,831,521 T C 0.560 − 0.204 0.039 1.30 × 10–7 0.82 0.997    
13 rs56015205 Spine BMD b-timing 10 3,142,278 A T 0.573 − 0.245 0.044 3.24 × 10–8   0.868 PFKP Novel  
  rs56015205 Spine BMC b-timing 10 3,142,278 A T 0.573 − 0.225 0.044 4.36 × 10–7   0.868    
14 rs11002218 Total hip BMC c-velocity 10 79,365,309 T C 0.939 − 0.491 0.088 3.34 × 10–8   0.997 KCNMA1 Known  
  rs11002218 TBLH BMC c-velocity 10 79,365,309 T C 0.939 − 0.451 0.089 4.94 × 10–7   0.997    
15 rs67416120 Femoral neck BMD b-timing 10 98,010,202 AAGAG A 0.292 − 0.271 0.048 2.22 × 10–8   0.955 BLNK Novel  
16 rs17140801 Femoral neck BMC c-velocity 16 6,680,114 C T 0.868 0.319 0.055 9.99 × 10–9   0.964 RBFOX1 Known  
17 16:75655176 Distal 1/3 radius BMD b-timing 16 75,655,176 C I 0.912 0.386 0.069 3.19 × 10–8   0.849 TERF2IP [P] Novel y
  rs78580335 Femoral neck BMC b-timing 16 75,787,356 T C 0.880 0.305 0.054 1.59 × 10–8 0.48 0.971    
18 rs1719484 Spine BMC a-size 17 72,547,434 C G 0.853 − 0.297 0.054 3.80 × 10–8   0.993 CD300C Novel  
19 rs72631380 Total hip BMC a-size 17 73,102,584 G T 0.948 0.428 0.077 3.91 × 10–8   0.952 SLC16A5 Novel  
  rs72631380 Femoral neck BMC a-size 17 73,102,584 G T 0.948 0.420 0.077 7.24 × 10–8   0.952    
20 rs10415015 Distal 1/3 radius BMC b-timing 19 4,818,488 C G 0.897 − 0.351 0.063 2.70 × 10–8   0.993 TICAM1 Novel  
21 rs116463118 Skull BMD b-timing 19 41,648,588 C T 0.939 − 0.527 0.095 3.47 × 10–8   0.825 CYP2F1 Known  
22e rs8130725 TBLH BMD b-timing 21 16,458,656 G C 0.929 0.397 0.071 3.17 × 10–8   0.939 NRIP1 Novel  
23e rs9974832 Distal 1/3 radius BMD a-size 21 16,524,340 C T 0.902 − 0.359 0.064 1.98 × 10–8   0.997 NRIP1 Novel  
24 rs72630065 Femoral neck BMC b-timing 23 72,080,371 C G 0.914 0.292 0.053 4.15 × 10–8   0.98 DMRTC1 Novel  
25 X:75657132 Femoral neck BMC b-timing 23 75,657,132 C T 0.939 0.521 0.088 4.74 × 10–9   0.631 SMARCA2 Novel  
  X:75657132 Femoral neck BMC a-size 23 75,657,132 C T 0.939 0.504 0.087 8.47 × 10–9   0.631    
  X:75657132 Femoral neck BMD a-size 23 75,657,132 C T 0.939 0.475 0.083 1.46 × 10–8   0.631    
26 X:76607583 Femoral neck BMC a-size 23 76,607,583 A G 0.073 − 0.353 0.057 1.01 × 10–9   0.952 FGF16 Novel  
  rs201392388 Femoral neck BMC a-size 23 76,607,584 G A 0.073 − 0.353 0.057 1.01 × 10–9   0.952    
  X:76607583 Total hip BMD a-size 23 76,607,583 A G 0.073 − 0.325 0.058 2.06 × 10–8   0.952    
  rs201392388 Total hip BMD a-size 23 76,607,584 G A 0.073 − 0.325 0.058 2.06 × 10–8   0.952    
27 rs144238538 Femoral neck BMC a-size 23 78,179,955 C T 0.911 0.291 0.052 3.03 × 10–8   0.981 P2RY10, Novel  
  rs144238538 Total hip BMD a-size 23 78,179,955 C T 0.911 0.287 0.052 4.75 × 10–8   0.981 MIR4328   
  rs7050494 Spine BMC b-timing 23 78,094,413 G T 0.897 0.271 0.049 4.97 × 10–8 0.55 0.978    
S1 rs17336942 TBLH BMD a-size 2 212,861,073 T C 0.581 0.195 0.038 3.74 × 10–7   0.996 ERBB4 Novel  
  rs17336942 Total hip BMD a-size 2 212,861,073 T C 0.581 0.190 0.038 8.38 × 10–7   0.996    
  rs17336942 Total hip BMC a-size 2 212,861,073 T C 0.581 0.191 0.038 6.64 × 10–7   0.996    
S2 rs77349060 Spine BMC c-velocity 2 240,273,229 C T 0.871 0.275 0.052 1.93 × 10–7   0.996 HDAC4 Novel  
  rs4852055 Total hip BMC c-velocity 2 240,281,878 A G 0.848 0.250 0.048 2.10 × 10–7 0.83 0.997    
S3 rs56883672 Femoral neck BMC c-velocity 4 106,026,989 C G 0.595 0.208 0.038 7.12 × 10–8   0.999 TET2 [P] Known  
  rs6533178 Total hip BMC c-velocity 4 106,039,826 T C 0.592 − 0.203 0.040 3.19 × 10–7 0.43 0.965    
S4 rs12641626 Femoral neck BMD a-size 4 169,760,004 G A 0.912 0.357 0.067 1.27 × 10–7   0.953 PALLD Novel y
  rs12641626 Femoral neck BMC a-size 4 169,760,004 G A 0.912 0.348 0.067 2.36 × 10–7   0.953    
S5 rs79651589 TBLH BMC a-size 6 143,130,718 C CTGTTTGTT 0.313 − 0.212 0.043 7.53 × 10–7   0.79 HIVEP2 Novel  
  rs79651589 Total hip BMC a-size 6 143,130,718 C CTGTTTGTT 0.313 − 0.213 0.043 9.26 × 10–7   0.79    
S6 rs142924645 Total hip BMD b-timing 12 3,162,566 C CT 0.943 − 0.425 0.085 7.02 × 10–7   0.964 TEAD4 Novel  
  rs185315462 Spine BMD b-timing 12 3,163,396 T G 0.945 − 0.440 0.087 4.67 × 10–7 1 0.964    
S7 rs45554832 TBLH BMC a-size 14 30,375,005 C T 0.930 − 0.400 0.075 1.09 × 10–7   0.922 PRKD1 Novel  
  rs45554832 Total hip BMD a-size 14 30,375,005 C T 0.930 − 0.394 0.076 2.22 × 10–7   0.922    
  rs45554832 Femoral neck BMD a-size 14 30,375,005 C T 0.930 − 0.413 0.076 6.07 × 10–8   0.922    
  rs45554832 Femoral neck BMC a-size 14 30,375,005 C T 0.930 − 0.393 0.076 2.39 × 10–7   0.922    
  rs74040635 Total hip BMC a-size 14 30,388,192 T C 0.943 − 0.449 0.085 1.36 × 10–7 0.6 0.922    
S8 rs9962766 TBLH BMC b-timing 18 71,009,151 G A 0.894 − 0.306 0.062 7.92 × 10–7   0.986 NETO1 Novel  
  rs10622698 TBLH BMC a-size 18 71,025,487 A ATT 0.862 − 0.290 0.056 2.58 × 10–7 0.8 0.995    
S9 rs77154151 TBLH BMC c-velocity 19 3,072,434 G A 0.877 0.332 0.065 4.08 × 10–7   0.795 AES Novel y
  rs12461372 Total hip BMC c-velocity 19 3,072,859 G A 0.880 0.331 0.064 2.13 × 10–7 0.99 0.796    
S10 rs4283509 Femoral neck BMD c-velocity 21 23,031,423 C A 0.882 0.292 0.057 3.79 × 10–7   0.995 NCAM2 Novel  
  21:23052938 Total hip BMC c-velocity 21 23,052,938 T TG 0.268 − 0.237 0.047 5.62 × 10–7 0.36 0.841    
S11 rs2564086 Spine BMC a-size 2 5,944,498 C T 0.274 0.225 0.045 5.21 × 10–7   0.98 SOX11 Noveld y
S12 rs10866634 Distal 1/3 radius BMC a-size 5 168,748,968 T G 0.145 0.268 0.054 9.14 × 10–7   0.991 SLIT3 Noveld  
S13 rs11195210 Total hip BMC a-size 10 112,357,813 G A 0.931 0.364 0.074 9.37 × 10–7   0.979 SMC3 Knownd  
  1. aAllele frequency in all samples (see ancestry-specific frequencies in Supplementary Table 6)
  2. bFor loci with more than one sentinel SNP, r2 values are given between this SNP and that in the row above
  3. cInfo represents imputation quality
  4. dSuggestive association with heel eBMD (P < 10−4) in Morris et al. 2018
  5. eDespite their close physical proximity, signals 22 and 23 are not in LD (r2 = 0.05)
  6. f[P] Genes implicated by promoter-interaction map
  7. gNot previously reported in GWAS of bone density
  8. hFull results presented in Supplementary Table 9. Y, nominal support