Table 1.
Genes significantly associated with breast cancer risk using the MiXcan or PrediXcan approaches in 58,648 women, and the corresponding S-PrediXcan and GWAS results in a larger sample of 228,951 women of European ancestry
| Gene Name | Cytoband | MiXcana | PrediXcanb | S-PrediXcanc | GWASd SNPs within 500 kb | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Epithelial | Stromal | Combined | |||||||||||||
| Effect | SE | P value | Effect | SE | P value | P value | Effect | SE | P value | Effect | SE | P value | |||
| Genes identified by both MiXcan and PrediXcan | |||||||||||||||
| CH17-437K3.1• | 1p11.2 | –1.62 | 0.28 | 7.3E–09 | –1.62 | 0.28 | 7.3E–09 | 7.3E–09 | –1.62 | 0.28 | 7.3E–09 | –0.56 | 0.05 | 3.1E–28*** | rs11249433 |
| SLC4A7• | 3p24.1 | 2.30 | 0.27 | 2.0E–17 | 2.30 | 0.27 | 2.0E–17 | 2.0E–17 | 2.30 | 0.27 | 2.0E–17 | 1.11 | 0.09 | 3.5E–38*** | rs4973768 |
| L3MBTL3• | 6q23.1 | –0.12 | 0.02 | 1.4E–08 | –0.12 | 0.02 | 1.4E–08 | 1.4E–08 | –0.12 | 0.02 | 1.4E–08 | –0.11 | 0.02 | 2.1E–11*** | rs6569648 |
| RCCD1• | 15q26.1 | –0.16 | 0.03 | 4.2E–07 | –0.16 | 0.03 | 4.2E–07 | 4.2E–07 | –0.16 | 0.03 | 4.2E–07 | –0.16 | 0.02 | 3.5E–11*** | rs2290203 |
| Genes identified by MiXcan only | |||||||||||||||
| MRPS30 | 5p12 | 3.00 | 0.67 | 6.8E–06 | –4.82 | 0.75 | 1.8E–10 | 3.5E–10 | –0.08 | 0.31 | 8.1E–01 | 0.50 | 0.04 | 3.3E–30*** | rs10941679 |
| SETD9 | 5q11.2 | 0.15 | 0.04 | 5.2E–04 | –0.57 | 0.10 | 4.2E–09 | 8.4E–09 | –0.07 | 0.02 | 1.8E–03 | –0.10 | 0.02 | 1.9E–08*** | rs62355902 |
| ADGRV1 | 5q14.3 | –0.27 | 0.05 | 3.6E–07 | 0.27 | 0.05 | 3.6E–07 | 3.6E–07 | NA | NA | NA | –0.09 | 0.15 | 5.5E–01 | rs10474352 |
| ZNF703 | 8p11.23 | –1.96 | 0.38 | 2.7E–07 | 1.59 | 0.27 | 2.4E–09 | 4.8E–09 | 0.07 | 0.08 | 3.9E–01 | 0.17 | 0.06 | 4.3E–03* | – |
| TMEM245 | 9q31.3 | –0.64 | 0.12 | 7.0E–08 | –0.30 | 0.10 | 2.2E–03 | 1.4E–07 | –0.42 | 0.14 | 3.4E–03 | 0.04 | 0.07 | 5.4E–01 | – |
| PRR33 | 11p15.5 | –1.41 | 0.28 | 5.2E–07 | 1.41 | 0.28 | 5.2E–07 | 5.2E–07 | NA | NA | NA | –1.39 | 0.14 | 1.4E–23*** | rs3817198 |
| CDYL2 | 16q23.2 | –0.13 | 0.03 | 9.1E–07 | –0.08 | 0.03 | 1.0E–03 | 1.8E–06 | –2.67 | 0.85 | 1.7E–03 | –0.10 | 0.04 | 3.7E–03* | rs13329835 |
| PSG4 | 19q13.31 | –0.16 | 0.04 | 3.0E–06 | 0.14 | 0.04 | 1.1E–04 | 5.9E–06 | 0.00 | 0.03 | 9.5E–01 | 0.01 | 0.01 | 5.3E–01 | – |
| Genes identified by PrediXcan only | |||||||||||||||
| SRGAP2C | 1p11.2 | –0.19 | 0.25 | 4.3E–01 | –0.58 | 0.28 | 4.1E–02 | 7.8E–02 | –0.65 | 0.11 | 1.8E–09 | –0.56 | 0.05 | 1.2E–28*** | rs11249433 |
| CASP8 | 2q33.1 | –0.65 | 0.30 | 2.7E–02 | 0.43 | 0.27 | 1.1E–01 | 4.4E–02 | –0.13 | 0.03 | 3.1E–06 | –0.11 | 0.02 | 3.1E–11*** | rs1830298 |
| ALS2CR12 | 2q33.1 | –0.10 | 0.12 | 4.0E–01 | 0.40 | 0.22 | 7.0E–02 | 1.3E–01 | 0.18 | 0.04 | 2.6E–06 | 0.15 | 0.02 | 4.2E–12*** | rs1830298 |
| STXBP4 | 17q22 | –0.06 | 0.07 | 4.1E–01 | 0.18 | 0.05 | 2.1E–04 | 4.2E–04 | 0.16 | 0.03 | 4.5E–06 | 0.32 | 0.03 | 3.4E–23*** | rs2787486 |
aGenes with a MiXcan combined p value < 7.7 × 10−6 (0.05/6461 genes tested) aggregating across epithelial and stromal (non-epithelial) cell types were considered statistically significant. • denotes same model for epithelial and stromal cell types in MiXcan.
bElastic net models were built using GTEx v8 mammary tissue data for 125 European ancestry women and all SNPs in the PredictDB database https://predictdb.org/. NA indicates that none of the SNPs evaluated were selected as predictors in the elastic net models for ADGRV1 and PRR33. Genes with a PrediXcan p value < 7.7 × 10−6 were considered statistically significant.
cS-PrediXcan33 was used to test associations of predicted GReX with breast cancer risk using GWAS summary statistics for 122,977 cases and 105,974 controls11. *** denotes p value < 7.7 × 10−6 and * denotes p value < 0.05.
dBreast cancer SNPs reported in a GWAS of 122,977 breast cancer cases and 105,974 controls11.