Table 1.
Characteristics of genetic variants associated with sex hormone- inding globulin (SHBG) and breast cancer in published GWAS
| SNPs | Chr: pos (hg19) | Locus | Effect/ref. allele | Circulating SHBG |
Body mass index |
Overall breast cancer |
ER+ve breast cancer |
ER-ve breast cancer |
|||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Betaa (SE) | P-value | Betab (SE) | P-value | Betac (SE) | P-value | Betac (SE) | P-value | Betac (SE) | P-value | ||||
| rs17496332 | 1: 107546375 | PRMT6 | G/A | 0.028 (0.0041) | 1.40E-11 | 0.0124 (0.0032) | 1.01E-04 | 0.0003 (0.0068) | 9.61E-01 | −0.0009 (0.0081) | 9.13E-01 | 0.0169 (0.0123) | 1.68E-01 |
| rs780093 | 2: 27742603 | GCKR | C/T | 0.032 (0.0039) | 2.20E-16 | 0.012 (0.0030) | 7.64E-05 | 0.0113 (0.0064) | 7.55E-02 | 0.0106 (0.0076) | 1.61E-01 | 0.0136 (0.0115) | 2.39E-01 |
| rs3779195 | 7: 97993362 | BAIAP2L1 | T/A | 0.028 (0.0051) | 2.70E-08 | −0.001 (0.0047) | 8.32E-01 | −0.0040 (0.0081) | 6.23E-01 | −0.0072 (0.0096) | 4.50E-01 | 0.0253 (0.0148) | 8.76E-02 |
| rs440837 | 8: 81461974 | ZBTB10 | G/A | 0.028 (0.0047) | 3.40E-09 | −0.0058 (0.0045) | 1.97E-01 | −0.0088 (0.0075) | 2.46E-01 | −0.0090 (0.0090) | 3.18E-01 | 0.0183 (0.0136) | 1.78E-01 |
| rs7910927 | 10: 65138910 | JMJD1C | G/T | 0.048 (0.0039) | 6.10E-35 | −0.0124 (0.0036) | 5.72E-04 | −0.0217 (0.0062) | 5.24E-04 | −0.0286 (0.0075) | 1.32E-04 | −0.0018 (0.0115) | 8.73E-01 |
| rs4149056 | 12: 21331549 | SLCO1B1 | T/C | 0.029 (0.0052) | 1.90E-08 | −0.0002 (0.004) | 9.51E-01 | −0.0098 (0.0084) | 2.45E-01 | −0.0115 (0.0100) | 2.49E-01 | −0.0130 (0.0153) | 3.93E-01 |
| rs8023580 | 15: 96708291 | NR2F2 | C/T | 0.030 (0.0044) | 8.30E-12 | −0.0008 (0.0042) | 8.49E-01 | −0.0085 (0.0076) | 2.61E-01 | −0.0144 (0.0090) | 1.09E-01 | 0.0067 (0.0135) | 6.20E-01 |
| rs2411984 | 17: 47445751 | ZNF652 | A/G | 0.033 (0.0044) | 3.50E-14 | 0.0001 (0.004) | 9.80E-01 | −0.0078 (0.0068) | 2.49E-01 | −0.0009 (0.0081) | 9.11E-01 | 0.0044 (0.0123) | 7.23E-01 |
| rs12150660 | 17: 7521915 | SHBG | T/G | 0.103 (0.0047) | 1.80E-106 | 0.0091 (0.0043) | 3.43E-02 | −0.0043 (0.0072) | 5.51E-01 | −0.0018 (0.0086) | 8.35E-01 | 0.0068 (0.0131) | 6.05E-01 |
| rs1641537 | 17: 7545721 | SHBG | C/T | 0.0814 (0.0062) | 8.19E-39 | −0.0014 (0.0054) | 7.95E-01 | −0.0042 (0.0094) | 6.52E-01 | −0.0139 (0.0111) | 2.11E-01 | 0.0317 (0.0173) | 6.67E-02 |
| rs1625895 | 17: 7578115 | TP53 | C/T | 0.052 (0.0067) | 1.17E-14 | 0.0134 (0.0059) | 2.31E-02 | 0.0209 (0.0093) | 2.42E-02 | 0.0209 (0.0111) | 6.00E-02 | 0.0191 (0.0170) | 2.61E-01 |
| rs1573036 | Χ: 109820068 | TDGF3 | T/C | 0.028 (0.0037) | 4.10E-14 | NA | NA | −0.0053 (0.0081) | 5.16E-01 | −0.0002 (0.0093) | 9.81E-01 | −0.0066 (0.0145) | 6.49E-01 |
GWAS, genome-wide association studies; SNPs, single nucleotide polymorphisms; Chr, chromosome; pos, position; SHBG, sex hormone binding globulin; ER, estrogen receptor; SE, standard error; NA, not available.
Beta units are per-allele effect estimates in natural logarithm-transformed SHBG concentrations (nmol/L).20 To enable better comparison with results from observational studies, we run MR analyses after transforming these beta coefficients into the natural scale (nmol/L) using a formula suggested by Rodriguez-Barranco and colleagues.25
Beta units are per standard deviation increase of body mass index (kg/m2).23
Per-allele logarithm of the odds ratios between breast cancer cases and controls.24