Table 3.
Summary effects from the overall analyses of case-control association studies for genetic variants associated with fracture occurrence risk in physically active participants including all studies and sex sub-groups.
| Genetic variant and risk comparison model | Sample size | Test of heterogeneity | Test of overall association | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Participants | Studies | Overall | Between sub-groups | FE/RE | OR (95% CI) | P | |||
| Fracture/Control (risk model frequency) | I2 | P | I2 | P | |||||
| COL1A1 Sp1(rs1800012) | |||||||||
| Allele Contrast: T | 772 (20%)/2514 (20%) | 4 | 17% | 0.30 | 67% | 0.05 | FE | 0.95 (0.76–1.19) | 0.66 |
| Recessive: TT+TG | 455 (32%)/1465 (31%) | 4 | 1% | 0.41 | 57% | 0.10 | FE | 0.99 (0.77–1.27) | 0.91 |
| Homozygote Contrast: TT | 455 (1.5%)/1465 (3%) | 4 | 0% | 0.70 | 0% | 0.63 | FE | 0.58 (0.25–1.32) | 0.19 |
| COL1A2 PvuII (rs412777) | |||||||||
| Allele Contrast: C | 342 (49%)/607 (51%) | 2 | 92% | <0.001 | 92% | <0.001 | RE | 1.81 (0.39–8.52) | 0.45 |
| Recessive: CC+CA | 229 (62%)/393 (62%) | 2 | 83% | 0.02 | 82% | 0.02 | RE | 1.81 (0.46–7.17) | 0.40 |
| Homozygote Contrast: CC | 229 (11%)/393 (16%) | 2 | 85% | 0.009 | 85% | 0.009 | RE | 0.87 (0.22–3.52) | 0.85 |
| CTR (rs1801197) | |||||||||
| Allele Contrast: T | 313 (90%)/767 (88%) | 3 | 0% | 0.56 | 0% | 0.88 | FE | 1.27 (0.82–1.97) | 0.29 |
| Recessive: TT+TC | 189 (92%)/477 (91%) | 3 | 0% | 0.68 | 0% | 0.96 | FE | 1.23 (0.67–2.27) | 0.51 |
| Homozygote Contrast: TT | 189 (57%)/477 (51%) | 3 | 25% | 0.26 | 38% | 0.20 | RE | 1.23 (0.81–1.87) | 0.33 |
| ESR1 PvuII (rs2234693) | |||||||||
| Allele Contrast: C | 119 (76%)/1455 (73%) | 2 | 0% | 0.41 | 44% | 0.18 | FE | 1.25 (0.80–1.95) | 0.33 |
| Recessive: CC+CT | 80 (83%)/953 (79%) | 2 | 0% | 0.79 | 0% | 0.49 | FE | 1.28 (0.69–2.35) | 0.43 |
| Homozygote Contrast: CC | 80 (31%)/953 (32%) | 2 | 48% | 0.14 | 73% | 0.05 | RE | 0.92 (0.43–1.98) | 0.84 |
| ESR1 XbaI (rs9340799) | |||||||||
| Allele Contrast: G | 124 (89%)/1519 (86%) | 2 | 68% | 0.04 | 0% | 0.81 | RE | 1.02 (0.35–3.00) | 0.96 |
| Recessive: GG+GA | 80 (91%)/953 (90%) | 2 | 33% | 0.23 | 0% | 0.80 | RE | 1.11 (0.40–3.09) | 0.85 |
| Homozygote Contrast: GG | 80 (46%)/953 (49%) | 2 | 4% | 0.35 | 0% | 0.49 | FE | 0.91 (0.57–1.45) | 0.69 |
| LRP5 (rs3736228) | |||||||||
| Allele Contrast: T | 345 (14%)/863 (13%) | 2 | 0% | 0.92 | 0% | 0.99 | FE | 1.14 (0.78–1.65) | 0.50 |
| Recessive: TT+TC | 195 (24%)/481 (22%) | 2 | 0% | 0.94 | 0% | 0.89 | FE | 1.18 (0.78–1.77) | 0.43 |
| Homozygote Contrast: TT | 195 (1%)/481 (1.6%)* | 2* | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| VDR FokI (rs10735810) | |||||||||
| Allele Contrast: C | 342 (60%)/774 (48%) | 3 | 76% | 0.006 | 0% | 0.33 | RE | 1.60 (0.82–3.11) | 0.17 |
| Recessive: CC+CT | 220 (69%)/494 (61%) | 3 | 61% | 0.05 | 0% | 0.36 | RE | 1.49 (0.76–2.91) | 0.25 |
| Homozygote Contrast: CC | 220 (24%)/494 (16%) | 3 | 0% | 0.71 | 0% | 0.86 | FE | 1.49 (0.98–2.26) | 0.06 |
| VDR ApaI (rs7975232) | |||||||||
| Allele Contrast: C | 229 (71%)/588 (70%) | 2 | 0% | 0.83 | 0% | 0.66 | FE | 1.07 (0.76–1.51) | 0.71 |
| Recessive: CC+CA | 152 (78%)/387 (76%) | 2 | 0% | 0.89 | 0% | 0.91 | FE | 1.09 (0.68–1.73) | 0.72 |
| Homozygote Contrast: CC | 152 (29%)/387 (29%) | 2 | 11% | 0.32 | 43% | 0.19 | FE | 0.92 (0.60–1.41) | 0.70 |
| VDR TaqI (rs731236) | |||||||||
| Allele Contrast: C | 332 (48%)/776 (48%) | 3 | 41% | 0.17 | 28% | 0.24 | RE | 1.05 (0.72–1.53) | 0.80 |
| Recessive: CC+CT | 218 (61%)/508 (60%) | 3 | 10% | 0.34 | 0% | 0.41 | FE | 1.01 (0.72–1.41) | 0.96 |
| Homozygote Contrast: CC | 218 (13%)/508 (13%) | 3 | 0% | 0.52 | 10% | 0.29 | FE | 0.98 (0.60–1.60) | 0.95 |
| VDR BsmI (rs1544410) | |||||||||
| Allele Contrast: T | 389 (62%)/2,002 (70%) | 4 | 47% | 0.09 | 0% | 0.54 | RE | 0.97 (0.68–1.39) | 0.87 |
| Recessive: TT+TG | 264 (72%)/1,306 (77%) | 4 | 0% | 0.50 | 0% | 0.90 | FE | 1.08 (0.79–1.49) | 0.62 |
| Homozygote Contrast: TT | 264 (19%)/1,306 (30%) | 4 | 25% | 0.25 | 0% | 0.94 | RE | 0.85 (0.60–1.21) | 0.37 |
RE, random effects; FE, fixed effects; OR, odds ratio; CI, confidence interval. Sample size describes frequency of case and control counts for each model with risk variant frequency in parentheses. *LRP5 (rs3736228) TT homozygotes present in only one of the two included studies. Values in bold indicate significant heterogeneity and/or associations with fracture risk.