Table 2.
Two-sample Mendelian randomization estimations showing the effect of smoking-related methylation on the risk of breast cancer subtypes (top ten CpGs according to p-value).
| CpG | Chr | Position | Method | SNPs | Odds ratio | 95% CI | p-value | q-value | Gene | Power | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| ER+ | |||||||||||
| cg2583948 | 15 | 75931953 | Wald ratio | 1 | 0.94 | 0.91 | 0.97 | 3.01E-05 | 1.03E-02 | IMP3 | 1.00 |
| cg0760265* | 17 | 80844196 | IVW | 2 | 1.07 | 1.03 | 1.11 | 2.19E-04 | 2.68E-02 | TBCD | 0.91 |
| cg0420946 | 17 | 4711018 | Wald ratio | 1 | 0.95 | 0.93 | 0.98 | 2.40E-04 | 2.74E-02 | PLD2 | 1.00 |
| cg2037583 | 13 | 99135543 | Wald ratio | 1 | 1.09 | 1.04 | 1.15 | 4.65E-04 | 3.99E-02 | STK24 | 0.97 |
| cg1227506 | 1 | 45279329 | Wald ratio | 1 | 0.93 | 0.89 | 0.97 | 8.06E-04 | 5.34E-02 | BTBD19 | 0.93 |
| cg2607605* | 5 | 421317 | IVW | 2 | 1.05 | 1.02 | 1.08 | 1.04E-03 | 5.95E-02 | AHRR | 0.79 |
| cg1782334 | 10 | 80848143 | Wald ratio | 1 | 1.04 | 1.02 | 1.07 | 1.62E-03 | 7.78E-02 | ZMIZ1 | 1.00 |
| cg0156570 | 14 | 103245090 | Wald ratio | 1 | 1.09 | 1.03 | 1.14 | 2.19E-03 | 9.07E-02 | TRAF3 | 0.97 |
| cg1870825 | 22 | 39545030 | Wald ratio | 1 | 0.96 | 0.94 | 0.99 | 2.82E-03 | 1.01E-01 | CBX7 | 0.97 |
| cg0318838 | 2 | 233245886 | Wald ratio | 1 | 0.93 | 0.88 | 0.97 | 3.39E-03 | 1.09E-01 | ALPP | 0.87 |
| ER- | |||||||||||
| cg2583948 | 15 | 75931953 | Wald ratio | 1 | 0.92 | 0.88 | 0.96 | 2.20E-04 | 8.47E-02 | IMP3 | 0.98 |
| cg1882444 | 15 | 89154058 | Wald ratio | 1 | 0.94 | 0.91 | 0.98 | 2.10E-03 | 3.64E-01 | MIR7-2 | 0.97 |
| cg1261648 | 11 | 62379063 | Wald ratio | 1 | 0.87 | 0.79 | 0.96 | 3.31E-03 | 4.25E-01 | ROM1 | 0.97 |
| cg2761893 | 8 | 71581788 | Wald ratio | 1 | 1.13 | 1.04 | 1.23 | 5.33E-03 | 4.91E-01 | XKR9 | 0.99 |
| cg2670350 | 2 | 113404661 | Wald ratio | 1 | 0.93 | 0.88 | 0.99 | 1.30E-02 | 5.77E-01 | SLC20A1 | 0.91 |
| cg1693695 | 17 | 57915665 | Wald ratio | 1 | 0.91 | 0.85 | 0.98 | 1.44E-02 | 5.84E-01 | TMEM49 | 0.90 |
| cg1782334 | 10 | 80848143 | Wald ratio | 1 | 1.05 | 1.01 | 1.09 | 1.60E-02 | 5.91E-01 | ZMIZ1 | 0.96 |
| cg1345216 | 13 | 96204518 | Wald ratio | 1 | 1.09 | 1.02 | 1.18 | 1.76E-02 | 5.96E-01 | CLDN10 | 0.82 |
| cg2403312 | 16 | 30485383 | Wald ratio | 1 | 1.04 | 1.01 | 1.07 | 1.81E-02 | 5.98E-01 | ITGAL | 0.84 |
| cg1858406 | 2 | 64975916 | Wald ratio | 1 | 0.91 | 0.84 | 0.98 | 1.98E-02 | 6.02E-01 | 0.78 | |
Bold font indicates the estimation passed the FDR test.
CI indicates confidence interval; IVW, Inverse variance weighted; ER, estrogen receptor; SNP, single nucleotide polymorphism. Statistical power was calculated by a web tool (https://shiny.cnsgenomics.com/mRnd/) (23).
* Cochran’s Q-test for cg0760265 (Q-statistics, 0.19; p = 0.66) and cg2607605 (Q-statistics, 0.05; p = 0.83).