TABLE 2.
Summary of conditional analysis at known breast cancer risk region
| Before conditional analysis |
After conditional analysis |
|||||||
|---|---|---|---|---|---|---|---|---|
| Gene | Number of SNPs | Number of significant SNPs | Index GWAS SNP p value | Number of significant SNPs | Index SNP | Smallest conditional p values | Ratioa | Magnitude of change in the minimum p value before and after COJO |
| ALS2CR12 | 480 | 12 | 8.2E–17 | 1 | rs3769823 | 6.40E–09 | 0.92 | 1.28E–08 |
| ATG10 | 619 | 24 | 6.9E–13 | 0 | rs891159 | 1.20E–07 | 1.00 | 5.75E–06 |
| ATP6AP1L | 581 | 24 | 6.9E–13 | 0 | rs891159 | 1.70E–07 | 1.00 | 4.06E–06 |
| CASP8 | 493 | 12 | 8.2E–17 | 6 | rs3769823 | 3.90E–12 | 0.50 | 2.10E–05 |
| CRHR1 | 229 | 13 | 1.5E–10 | 0 | rs17763086 | 1.40E–05 | 1.00 | 1.07E–05 |
| CRHR1-IT1 | 230 | 13 | 1.5E–10 | 0 | rs17763086 | 9.90E–05 | 1.00 | 1.52E–06 |
| HIST2H2BA | 202 | 19 | 3.5E–52 | 1 | rs11249433 | 7.40E–24 | 0.95 | 4.73E–29 |
| KANSL1-AS1 | 34 | 13 | 1.5E–10 | 0 | rs17763086 | 1.60E–01 | 1.00 | 9.38E–10 |
| L3MBTL3 | 724 | 13 | 1.7E–12 | 0 | rs6569648 | 1.40E–03 | 1.00 | 1.21E–09 |
| LRRC37A | 285 | 13 | 1.5E–10 | 0 | rs17763086 | 4.60E–05 | 1.00 | 3.26E–06 |
| LRRC37A4P | 285 | 13 | 1.5E–10 | 0 | rs17763086 | 4.60E–05 | 1.00 | 3.26E–06 |
| MRPL23-AS1 | 557 | 36 | 2.4E–33 | 18 | rs569550 | 1.20E–29 | 0.50 | 2.00E–04 |
| NUDT17 | 112 | 17 | 1.5E–10 | 0 | rs36107432 | 3.90E–05 | 1.00 | 3.85E–06 |
| RP11-15A1.7 | 594 | 32 | 1E–16 | 0 | rs10426528 | 4.60E–07 | 1.00 | 2.17E–10 |
| RP11-250B2.5 | 503 | 8 | 2.7E–09 | 0 | rs9343989 | 1.00E–03 | 1.00 | 2.70E–06 |
| RP11-554A11.9 | 532 | 36 | 2.8E–44 | 33 | rs680618 | 2.80E–44 | 0.08 | 1.00E+00 |
| RP11-73O6.3 | 665 | 13 | 1.7E–12 | 0 | rs6569648 | 1.70E–03 | 1.00 | 1.00E–09 |
| STXBP4 | 687 | 46 | 2E–28 | 0 | rs244353 | 2.10E–04 | 1.00 | 9.52E–25 |
| ZNF155 | 597 | 32 | 1E–16 | 5 | rs10426528 | 2.00E–09 | 0.84 | 5.00E–08 |
| ZNF404 | 551 | 32 | 1E–16 | 0 | rs10426528 | 5.30E–07 | 1.00 | 1.89E–10 |
| LRRC37A2 | 152 | 2 | 2E–08 | 0 | rs199498 | 1.80E–02 | 1.00 | 1.11E–06 |
Abbreviations: COJO, conditional and joint; GWAS, genome-wide association studies; SNP, single nucleotide polymorphisms.
Proportion of marginally significant SNPs that are not significant in conditional analyses. Analysis was performed using GWAS summary statistics of ER+ subtypes. The difference between marginal SNP tests for association (GWAS p values) and the SNP p values conditional on significant TWAS genes provides some evidence regarding the independence of the TWAS and single-SNP association signals. The number and proportion of SNPs that are genome-wide significant before and after conditioning on a TWAS-significant gene summarizes the degree single-SNP associations are dependent on (or independent of) the TWAS association.