Associations between SNPs reaching gene-wide significance with overall, ER+, and ER− breast cancer risk in the AMBER consortium
| Gene | SNP | Function | Ref/variant allele | MAF | PLINK INFO score | All cases | ER+ | ER− | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Per allele OR (95% CI) | Gene-wide Padj | Per allele OR (95% CI) | Gene-wide Padj | Per allele OR (95% CI) | Gene-wide Padj | ||||||
| All women | |||||||||||
| IL2RB | rs228952 | Intronic | G/T | 0.28 | 0.97 | 0.85 (0.79–0.92) | 0.007 | 0.88 (0.80–0.96) | 0.967 | 0.80 (0.71–0.90) | 0.051 |
| POU2AF1 | rs145624147 | Intronic | CAG/C | 0.24 | 1.01 | 0.85 (0.79–0.92) | 0.008 | 0.88 (0.80–0.96) | 0.549 | 0.82 (0.73–0.93) | 0.149 |
| rs1815948 | Intronic | G/C | 0.14 | 1.01 | 0.83 (0.75–0.92) | 0.023 | 0.85 (0.76–0.96) | 0.868 | 0.83 (0.71–0.93) | 1.000 | |
| rs76988807 | Intronic | T/C | 0.08 | 1.00 | 0.80 (0.70–0.90) | 0.035 | 0.79 (0.67–0.91) | 0.180 | 0.86 (0.71–1.03) | 1.000 | |
| HLA-DQA1 | rs12722043 | Exonic syn SNV | C/T | 0.25 | 0.98 | 0.85 (0.79–0.92) | 0.010 | 0.86 (0.78–0.94) | 0.287 | 0.83 (0.74–0.94) | 0.486 |
| rs115976249 | Intronic | G/A | 0.07 | 0.94 | 0.76 (0.66–0.87) | 0.012 | 0.77 (0.65–0.91) | 0.369 | 0.75 (0.61–0.92) | 1.000 | |
| TLR6 | rs141273518 | Intronic | C/T | 0.05 | 0.86 | 1.39 (1.18–1.65) | 0.017 | 1.33 (1.08–1.63) | 1.000 | 1.63 (1.27–2.08) | 0.015 |
| rs141628846 | Upstream | G/A | 0.02 | 0.97 | 1.68 (1.28–2.20) | 0.024 | 1.61 (1.16–2.22) | 0.556 | 2.02 (1.39–2.96) | 0.037 | |
| ATP6AP2 | rs115047524 | Intronic | G/A | 0.09 | 0.98 | 0.80 (0.72–0.90) | 0.025 | 0.82 (0.71–0.95) | 0.639 | 0.80 (0.67–0.96) | 1.000 |
| IL21 | rs76526843 | Intergenic | G/T | 0.02 | 0.90 | 0.64 (0.49–0.83) | 0.028 | 0.74 (0.54–1.00) | 1.000 | 0.65 (0.42–0.98) | 1.000 |
| CADM1 | rs73570052 | Intronic | A/C | 0.04 | 0.97 | 1.43 (1.20–1.70) | 0.052 | 1.41 (1.14–1.74) | 0.843 | 1.58 (1.23–2.05) | 0.274 |
| BCL3 | rs34698726 | Intergenic | A/T | 0.32 | 0.91 | 1.16 (1.08–1.25) | 0.010 | 1.19 (1.09–1.30) | 0.013 | 1.11 (0.99–1.25) | 1.000 |
| IL8 | rs188246983 | Intergenic | T/C | 0.07 | 0.99 | 1.17 (1.03–1.34) | 0.914 | 1.14 (0.97–1.34) | 1.000 | 1.49 (1.23–1.81) | 0.002 |
| rs113976067 | Intergenic | T/C | 0.22 | 1.00 | 1.10 (1.01–1.19) | 1.000 | 1.08 (0.98–1.19) | 1.000 | 1.23 (1.09–1.39) | 0.047 | |
| MAP3K1 | rs863839 | Intronic | A/G | 0.08 | 1.00 | 0.96 (0.84–1.09) | 1.000 | 1.08 (0.93–1.25) | 1.000 | 0.65 (0.53–0.81) | 0.003 |
| rs191188130 | Intronic | G/T | 0.09 | 0.87 | 1.03 (0.91–1.17) | 1.000 | 0.95 (0.81–1.11) | 1.000 | 1.32 (1.10–1.58) | 0.052 | |
| PRKDC | rs148411126 | Intronic | C/CT | 0.08 | 0.98 | 1.16 (1.03–1.32) | 1.000 | 1.03 (0.89–1.19) | 1.000 | 1.45 (1.22–1.72) | 0.003 |
| rs8178033 | Exonic nonsyn SNV | G/C | 0.08 | 1.00 | 1.15 (1.02–1.30) | 1.000 | 1.02 (0.88–1.19) | 1.000 | 1.41 (1.19–1.68) | 0.011 | |
| rs56411879 | Intronic | T/C | 0.02 | 0.86 | 1.16 (0.91–1.48) | 1.000 | 0.93 (0.69–1.26) | 1.000 | 1.81 (1.31–2.50) | 0.039 | |
| Premenopausal | |||||||||||
| SLA2 | rs221310 | Intronic | A/G | 0.73 | gtyped | 1.32 (1.16–1.51) | 0.003 | 1.26 (1.08–1.48) | 0.354 | 1.28 (1.06–1.56) | 0.949 |
| CXCR4 | rs17848049 | Intergenic | G/C | 0.09 | 1.00 | 0.65 (0.52–0.80) | 0.004 | 0.59 (0.45–0.78) | 0.009 | 0.74 (0.54–1.01) | 1.000 |
| PRG3 | rs4411290 | Intergenic | C/G | 0.47 | 1.00 | 0.79 (0.70–0.89) | 0.007 | 0.76 (0.66–0.89) | 0.016 | 0.84 (0.71–1.00) | 1.000 |
| rs1867128 | Intergenic | A/T | 0.51 | 1.00 | 0.81 (0.72–0.92) | 0.039 | 0.78 (0.67–0.91) | 0.043 | 0.86 (0.72–1.03) | 1.000 | |
| IL21 | rs115698762 | Intergenic | C/T | 0.02 | 0.94 | 2.22 (1.45–3.41) | 0.008 | 2.19 (1.33–3.60) | 0.064 | 2.02 (1.07–3.79) | 0.934 |
| rs143266239 | Intergenic | G/A | 0.04 | 0.97 | 1.77 (1.29–2.43) | 0.013 | 1.80 (1.25–2.60) | 0.053 | 1.67 (1.06–2.65) | 0.914 | |
| HLA-DMA | rs580962 | Intergenic | C/T | 0.78 | gtyped | 1.29 (1.12–1.49) | 0.016 | 1.42 (1.19–1.70) | 0.004 | 1.19 (0.96–1.46) | 1.000 |
| LBP | rs2232587 | Intronic | T/C | 0.11 | 0.96 | 0.68 (0.56–0.83) | 0.025 | 0.64 (0.50–0.82) | 0.079 | 0.73 (0.55–0.98) | 1.000 |
| MAP3K1 | rs252911 | Intergenic | A/G | 0.83 | 0.99 | 1.22 (1.04–1.43) | 1.000 | 1.45 (1.18–1.77) | 0.043 | 1.03 (0.82–1.29) | 1.000 |
| IL10 | chr1:206953202:I | Intergenic | T/TC | 0.11 | 0.92 | 1.21 (1.00–1.48) | 1.000 | 1.06 (0.83–1.35) | 1.000 | 1.73 (1.32–2.26) | 0.005 |
| rs140929284 | Intergenic | TC/T | 0.06 | 0.88 | 1.27 (0.98–1.63) | 1.000 | 1.10 (0.80–1.52) | 1.000 | 1.88 (1.35–2.63) | 0.015 | |
| rs74148793 | Intergenic | C/T | 0.15 | 0.99 | 1.21 (1.02–1.42) | 0.990 | 1.12 (0.92–1.37) | 1.000 | 1.50 (1.19–1.88) | 0.035 | |
| IL8 | rs113976067 | Intergenic | T/C | 0.21 | 1.00 | 1.20 (1.04–1.38) | 0.660 | 1.15 (0.97–1.37) | 1.000 | 1.50 (1.21–1.85) | 0.008 |
| rs188246983 | Intergenic | T/C | 0.07 | 0.99 | 1.25 (0.99–1.58) | 1.000 | 1.20 (0.91–1.60) | 1.000 | 1.78 (1.29–2.45) | 0.022 | |
| CADM1 | rs143193835 | Intronic | G/C | 0.03 | 0.99 | 1.74 (1.22–2.47) | 0.091 | 1.45 (0.94–2.23) | 1.000 | 2.65 (1.69–4.17) | 0.016 |
| HELLS | rs200175744 | Intergenic | ACT/A | 0.32 | 0.96 | 1.11 (0.97–1.26) | 1.000 | 1.03 (0.88–1.20) | 1.000 | 1.43 (1.18–1.72) | 0.017 |
| rs10882476 | Intronic | T/G | 0.09 | 0.99 | 1.05 (0.85–1.30) | 0.990 | 0.86 (0.66–1.13) | 1.000 | 1.64 (1.23–2.17) | 0.049 | |
| rs11188009 | Intergenic | A/G | 0.47 | 0.98 | 1.08 (0.96–1.22) | 1.000 | 1.00 (0.87–1.16) | 1.000 | 1.38 (1.16–1.66) | 0.032 | |
| Postmenopausal | |||||||||||
| POU2AF1 | rs75716067 | Intronic | A/G | 0.03 | 1.02 | 0.53 (0.40–0.71) | 0.002 | 0.46 (0.32–0.66) | 0.003 | 0.60 (0.38–0.93) | 1.000 |
| HLA-DQA1 | rs115976249 | Intronic | G/A | 0.07 | 0.94 | 0.66 (0.54–0.80) | 0.004 | 0.70 (0.56–0.88) | 0.359 | 0.61 (0.45–0.83) | 0.332 |
| IL21 | rs2390350 | Intronic | A/G | 0.51 | 1.00 | 1.19 (1.08–1.30) | 0.008 | 1.16 (1.04–1.29) | 0.236 | 1.16 (1.00–1.33) | 1.000 |
| rs17005895 | Intergenic | A/T | 0.15 | 0.97 | 1.27 (1.11–1.44) | 0.014 | 1.21 (1.03–1.41) | 0.363 | 1.32 (1.08–1.61) | 0.160 | |
| CYP4F11 | rs4572524 | Intergenic | A/G | 0.65 | 0.87 | 0.82 (0.73–0.90) | 0.015 | 0.84 (0.74–0.95) | 0.560 | 0.80 (0.68–0.93) | 0.659 |
| IL2RB | rs73406995 | Intergenic | C/G | 0.16 | 0.97 | 0.78 (0.68–0.88) | 0.021 | 0.77 (0.66–0.90) | 0.186 | 0.71 (0.58–0.87) | 0.207 |
| UBE2N | rs76506230 | Intergenic | T/C | 0.02 | 0.77 | 2.12 (1.40–3.22) | 0.026 | 2.52 (1.57–4.03) | 0.008 | 2.13 (1.18–3.86) | 0.814 |
| CASP8 | rs55637196 | Intronic | G/A | 0.20 | 0.99 | 0.81 (0.72–0.91) | 0.034 | 0.78 (0.68–0.90) | 0.065 | 0.81 (0.67–0.97) | 1.000 |
| IRAK2 | rs149858020 | Intronic | C/T | 0.13 | 0.99 | 1.31 (1.14–1.50) | 0.038 | 1.23 (1.05–1.45) | 1.000 | 1.51 (1.24–1.85) | 0.017 |
| CD274 | rs2890657 | Intronic | G/C | 0.04 | 0.97 | 0.75 (0.59–0.95) | 1.000 | 0.56 (0.42–0.76) | 0.016 | 0.84 (0.59–1.20) | 1.000 |
| rs10481593 | Intronic | G/A | 0.24 | gtyped | 0.87 (0.78–0.97) | 0.655 | 0.80 (0.70–0.91) | 0.040 | 0.91 (0.77–1.07) | 1.000 | |
| CALCA | rs34587547 | Exonic nonsyn SNV | C/G | 0.01 | 0.99 | 2.23 (1.26–4.29) | 0.130 | 3.20 (1.67–6.16) | 0.024 | 1.50 (0.54–4.13) | 1.000 |
| XCR1 | rs2373148 | Intergenic | T/C | 0.85 | 1.01 | 0.85 (0.75–0.96) | 0.361 | 0.78 (0.67–0.90) | 0.026 | 0.89 (0.73–1.07) | 1.000 |
| rs2371 | Upstream | A/G | 0.91 | 0.98 | 0.82 (0.70–0.96) | 0.382 | 0.73 (0.61–0.88) | 0.033 | 0.85 (0.67–1.08) | 1.000 | |
| PRKDC | rs8178153 | Intronic | C/T | 0.08 | 0.96 | 1.26 (1.06–1.50) | 1.000 | 1.09 (0.88–1.34) | 1.000 | 1.60 (1.24–2.06) | 0.028 |
| CD247 | rs12066323 | Intronic | G/A | 0.13 | 0.98 | 1.12 (0.97–1.28) | 1.000 | 0.98 (0.83–1.15) | 1.000 | 1.49 (1.22–1.82 | 0.037 |
| SMAD3 | rs2289259 | Intronic | G/A | 0.34 | 1.00 | 1.08 (0.98–1.19) | 1.000 | 1.00 (0.90–1.12) | 1.000 | 1.34 (1.15–1.55) | 0.049 |
NOTE: P-values for SNPs with corrected gene-wide significance at P ≤ 0.05 are indicated in bold text.
Abbreviations: gtyped: genotyped; MAF, minor allele frequency; Ref: referent; nonsyn SNV: nonsynonymous single nucleotide variant; syn SNV: synonymous single nucleotide variant.