Table 2.
Prostate cancer genome-wide association study results for new risk indel rs4646284 at 6q25.3 and for risk SNP rs2659124 at 19q13.33. These variants were detected in the KP study population and tested for replication in the PEGASUS and MEC cohorts. (a) Single variant and conditional analyses for 6q25.3 indel rs4646284 and the previous prostate cancer risk SNPs rs9364554 and rs651164. (b) Single variant and conditional analyses for 19q13.33 SNP rs2659124 detected here and the previous prostate cancer risk SNP rs2735839. Meta-analysis is given for the fixed effects (FE) and random effects (RE) analysis. Chromosome positions are given in b37. The risk allele frequency (RAF) is the pooled frequency across both cases and controls.
| (a)
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|---|---|---|---|---|---|---|---|---|---|
| No Conditioning | Conditioning on other 6q25.3 SNPs | ||||||||
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| Variant | Risk Allele | Ref. Allele | Group | Risk AF | OR (95% CI) | p | OR (95% CI) | p | r2info |
| Indel: rs4646284 | TG (indel) | T | KP NH white | 0.298 | 1.17 (1.12, 1.23) | 6.7×10−11 | 1.16 (1.10, 1.23) | 3.3×10−7 | 0.91 |
| KP Latino | 0.250 | 1.13 (0.94, 1.36) | 0.20 | 1.06 (0.85, 1.31) | 0.61 | 0.89 | |||
| KP Asian | 0.324 | 1.03 (0.84, 1.27) | 0.76 | 0.91 (0.68, 1.23) | 0.56 | 0.89 | |||
| KP Af-Amer | 0.365 | 1.18 (1.02, 1.37) | 0.029 | 1.21 (1.03, 1.42) | 0.020 | 0.85 | |||
| KP Meta FE | - | 1.17 (1.12, 1.22) | 5.5×10−12 | 1.15 (1.09, 1.21) | 8.5×10−8 | - | |||
| KP Meta RE | - | 1.17 (1.12, 1.22) | 5.5×10−12 | 1.15 (1.07, 1.22) | 7.7×10−5 | - | |||
| MEC | 0.361 | 1.13 (1.03, 1.25) | 0.0094 | 1.13 (1.03, 1.25) | 0.014 | 0.81 | |||
| PEGASUS | 0.278 | 1.27 (1.17, 1.37) | 1.4×10−8 | 1.20 (1.09, 1.32) | 0.00024 | 0.80 | |||
| Overall Meta FE | - | 1.18 (1.14, 1.22) | 1.0×10−19 | 1.16 (1.11, 1.21) | 5.4×10−12 | - | |||
| Overall Meta RE | - | 1.18 (1.13, 1.23) | 9.8×10−17 | 1.16 (1.11, 1.21) | 5.4×10−12 | - | |||
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| Previous SNP: rs9364554 | T | C | KP NH white | 0.279 | 1.10 (1.05, 1.15) | 6.6×10−5 | 1.05 (1.00, 1.10) | 0.070 | 1.00 |
| KP Latino | 0.227 | 1.16 (0.97, 1.29) | 0.1 | 1.13 (0.93, 1.36) | 0.21 | 1.00 | |||
| KP Asian | 0.319 | 1.06 (0.87, 1.29) | 0.59 | 1.05 (0.86, 1.28) | 0.63 | 1.00 | |||
| KP Af-Amer | 0.079 | 1.14 (0.89, 1.47) | 0.3 | 1.11 (0.85, 1.43) | 0.45 | 1.00 | |||
| KP Meta FE | - | 1.10 (1.06, 1.15) | 1.1×10−5 | 1.06 (1.01, 1.11) | 0.019 | - | |||
| KP Meta RE | - | 1.10 (1.06, 1.15) | 1.1×10−5 | 1.06 (1.01, 1.11) | 0.019 | - | |||
| MEC | 0.074 | 1.21 (1.02, 1.41) | 0.024 | 1.19 (1.00, 1.40) | 0.041 | 1.00 | |||
| PEGASUS | 0.293 | 1.22 (1.13, 1.31) | 9.3×10−8 | 1.16 (1.07, 1.25) | 0.00022 | 1.00 | |||
| Overall Meta FE | - | 1.14 (1.10, 1.18) | 6.3×10−12 | 1.09 (1.05, 1.13) | 1.9×10−5 | - | |||
| Overall Meta RE | - | 1.15 (1.09, 1.20) | 6.1×10−8 | 1.10 (1.05, 1.15) | 0.00014 | - | |||
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| Previous SNP: rs651164 | A | G | KP NH white | 0.308 | 0.94 (0.90, 0.98) | 0.0088 | 1.01 (0.96, 1.06) | 0.79 | 1.00 |
| KP Latino | 0.380 | 0.88 (0.75, 1.04) | 0.12 | 0.91 (0.76, 1.09) | 0.29 | 1.00 | |||
| KP Asian | 0.515 | 0.91 (0.76, 1.10) | 0.35 | 0.85 (0.65, 1.11) | 0.24 | 1.00 | |||
| KP Af-Amer | 0.264 | 1.02 (0.88, 1.18) | 0.82 | 1.08 (0.93, 1.28) | 0.30 | 1.00 | |||
| KP Meta FE | - | 0.94 (0.90, 0.98) | 0.0037 | 1.00 (0.96, 1.05) | 0.96 | - | |||
| KP Meta RE | - | 0.94 (0.90, 0.98) | 0.0037 | 1.00 (0.93, 1.07) | 0.90 | - | |||
| MEC | 0.307 | 0.98 (0.90, 1.08) | 0.73 | 1.03 (0.93, 1.13) | 0.60 | 1.00 | |||
| PEGASUS | 0.306 | 0.91 (0.84, 0.97) | 0.0065 | 0.99 (0.92, 1.07) | 0.82 | 1.00 | |||
| Overall Meta FE | - | 0.94 (0.91, 0.97) | 0.00019 | 1.00 (0.97, 1.04) | 0.89 | - | |||
| Overall Meta RE | - | 0.94 (0.91, 0.97) | 0.00019 | 1.00 (0.97, 1.04) | 0.89 | - | |||
| (b)
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|---|---|---|---|---|---|---|---|---|---|
| No Conditioning | Conditioning on other 19q13.33 SNPs | ||||||||
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| SNP | Risk Allele | Ref. Allele | Study Group | Risk AF | OR (95% CI) | p-value | OR (95% CI) | p-value | r2info |
| Risk SNP: rs2659124 | T | A | KP NH white | 0.854 | 1.22 (1.14, 1.30) | 2.2×10−9 | 1.13 (1.04, 1.23) | 0.0043 | 0.99 |
| KP Latino | 0.809 | 1.31 (1.07, 1.61) | 0.0099 | 1.36 (1.00, 1.86) | 0.053 | 0.99 | |||
| KP Asian | 0.587 | 1.15 (0.95, 1.40) | 0.15 | 1.03 (0.62, 1.71) | 0.91 | 0.98 | |||
| KP Af-Amer | 0.847 | 1.28 (1.05, 1.57) | 0.013 | 1.29 (1.05, 1.59) | 0.014 | 0.95 | |||
| KP Meta FE | - | 1.22 (1.15, 1.29) | 1.9×10−12 | 1.16 (1.07, 1.25) | 9.2×10−5 | - | |||
| KP Meta RE | - | 1.22 (1.15, 1.29) | 1.9×10−12 | 1.16 (1.07, 1.25) | 9.2×10−5 | - | |||
| MEC | 0.839 | 1.06 (0.94, 1.20) | 0.33 | 1.09 (0.97, 1.23) | 0.16 | 0.89 | |||
| PEGASUS | 0.868 | 1.16 (1.05, 1.28) | 0.0027 | 1.15 (1.01, 1.31) | 0.031 | 1.00 | |||
| Overall Meta FE | - | 1.18 (1.13, 1.24) | 1.3×10−13 | 1.14 (1.08, 1.21) | 4.3×10−6 | - | |||
| Overall Meta RE | - | 1.18 (1.12, 1.24) | 3.0×10−10 | 1.14 (1.08, 1.21) | 4.3×10−6 | - | |||
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| Previous SNP: rs2735839 | T | C | KP NH white | 0.150 | 1.20 (1.13, 1.28) | 1.6×10−8 | 1.11 (1.02, 1.23) | 0.016 | 1.00 |
| KP Latino | 0.214 | 1.21 (1.00, 1.47) | 0.052 | 0.97 (0.72, 1.30) | 0.83 | 1.00 | |||
| KP Asian | 0.419 | 1.15 (0.95, 1.40) | 0.15 | 1.13 (0.68, 1.88) | 0.63 | 1.00 | |||
| KP Af-Amer | 0.302 | 1.02 (0.88, 1.18) | 0.70 | 0.98 (0.84, 1.14) | 0.75 | 1.00 | |||
| KP Meta FE | - | 1.17 (1.11, 1.24) | 5.7×10−9 | 1.07 (1.00, 1.15) | 0.056 | - | |||
| KP Meta RE | - | 1.16 (1.07, 1.25) | 0.00012 | 1.07 (1.00, 1.15) | 0.056 | - | |||
| MEC | 0.311 | 0.93 (0.85, 1.02) | 0.11 | 0.91 (0.83, 1.00) | 0.058 | 1.00 | |||
| PEGASUS | 0.140 | 0.90 (0.82. 0.99) | 0.038 | 0.99 (0.88, 1.13) | 0.92 | 0.99 | |||
| Overall Meta FE | - | 0.88 (0.85, 0.92) | 2.0×10−10 | 1.01 (0.96, 1.06) | 0.76 | - | |||
| Overall Meta RE | - | 0.89 (0.84, 0.93) | 3.5×10−6 | 1.00 (0.92, 1.09) | 0.99 | - | |||
Pairwise correlations of these three SNPs in European, Latino, East Asian and African-Americans, respectively (KP data):
| r2rs4646284,rs9364554 | = 0.15, 0.090, 0.00028, 0.017; |
| r2rs4646284,rs651164 | = 0.19, 0.19, 0.53, 0.10; |
| r2rs4646284,rs9364559 | = 0.00047, 0.0088, 0.0018, 0.0010. |
Pairwise correlations of these two SNPs in European, Latino, East Asian and African-Americans, respectively (KP data): r2rs2659124, rs2735839 = 0.50, 0.58, 0.85, 0.055.