Overall meta-analysis of association estimates of autophagy-related risk variants for CLL
| SNP . | Gene . | Chr . | Effect allele . | Discovery meta-analysis . | CRuCIAL cohort . | Overall meta-analysis . | References (PMID) . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (N = 724 567 healthy controls; 4272 CLL cases) . | (N = 1898 healthy controls; 1200 CLL cases) . | (N = 726 465 healthy controls; 5472 CLL cases) . | ||||||||||
| OR (95% CI) . | P value . | PHet . | OR (95% CI) . | P value . | OR (95% CI) . | P value . | PHet . | |||||
| rs59952010 | ARSB | 5 | T | 1.13 (1.06-1.19) | 6.29E−05 | 0.831 | – | – | – | – | – | 26956414 |
| rs210143 | BAK1 | 6 | C | 1.20 (1.13-1.27) | 3.39E−09 | 0.083 | – | – | – | – | – | 22700719; 24292274; 23770605; 28165464 |
| rs4987852 | BCL2 | 18 | C | 1.38 (1.26-1.51) | 5.40E−12 | 0.148 | – | – | – | – | – | 23770605 |
| rs4987856 | BCL2 | 18 | T | 0.72 (0.66-0.80) | 7.35E−11 | 0.518 | – | – | – | – | – | 26956414; 23770605 |
| rs1026825 | BCL2 | 18 | G | 1.12 (1.06-1.18) | 6.62E−05 | 0.672 | 1.06 (0.94-1.19) | .353 | 1.11 (1.06-1.16) | 1.75E−05 | 0.698 | – |
| rs11152374 | BCL2 | 18 | A | 1.12 (1.05-1.20) | 5.42E−04 | 0.377 | 0.97 (0.84-1.13) | .716 | 1.10 (1.04-1.16) | 1.13E−03 | 0.193 | – |
| rs11839271 | LPAR6, RB1 | 13 | T | 0.90 (0.85-0.96) | 4.34E−04 | 0.991 | 1.13 (0.96-1.33)∗ | .131 | 0.92 (0.88-0.97) | 1.63E−03 | 0.268 | – |
| rs12457371 | BCL2 | 18 | G | 0.88 (0.83-0.93) | 2.77E−05 | 0.988 | 0.92 (0.78-1.08) | .294 | 0.89 (0.84-0.93) | 3.69E−06 | 0.989 | – |
| rs143052840 | PRKCD | 3 | A | 1.26 (1.11-1.42) | 1.80E−04 | 0.339 | 0.82 (0.62-1.00)∗ | .152 | 1.18 (1.06-1.31) | 1.59E−03 | 0.027 | – |
| rs3731204 | CDKN2A | 9 | C | 0.78 (0.72-0.85) | 1.03E−09 | 0.972 | 0.80 (0.67-0.94) | 8.72E−03 | 0.78 (0.73-0.84) | 1.57E−12 | 0.982 | – |
| rs4940571 | BCL2 | 18 | G | 1.18 (1.08-1.29) | 3.05E−04 | 0.969 | 1.40 (1.15-1.71) | 8.66E−04 | 1.21 (1.12-1.31) | 3.25E−06 | 0.445 | – |
| rs1926194 | FAS | 10 | A | 1.29 (1.23-1.36) | 4.73E−21 | 0.145 | – | – | – | – | – | 24292274; 26956414; 28165464 |
| rs7584971 | ITGA6 | 2 | A | 1.17 (1.07-1.29) | 6.07E−04 | 0.578 | – | – | – | – | – | 32887889 |
| rs4947976 | EGFR | 7 | A | 1.15 (1.07-1.24) | 1.15E−04 | 0.780 | 1.02 (0.91-1.14)† | .723 | 1.11 (1.05-1.17) | 4.04E−04 | 0.360 | – |
| rs6829366 | NAF1 | 4 | T | 1.12 (1.05-1.20) | 4.26E−04 | 0.022 | 1.14 (0.98-1.31) | .087 | 1.12 (1.06-1.19) | 5.73E−05 | 0.024 | – |
| rs6910366 | TFEB | 6 | G | 0.86 (0.80-0.93) | 8.28E−05 | 0.850 | 1.07 (0.85-1.33)∗ | .574 | 0.87 (0.82-0.93) | 8.74E−05 | 0.474 | – |
| rs7236090 | BCL2 | 18 | C | 1.11 (1.05-1.17) | 1.92E−04 | 0.896 | 0.99 (0.88-1.12) | .912 | 1.10 (1.04-1.15) | 1.83E−04 | 0.746 | – |
| rs2645488 | VMP1 | 17 | G | 1.11 (1.04-1.18) | 7.71E−04 | 0.043 | – | – | – | – | – | 31407831 |
| rs17885803 | WRAP53, TP53 | 17 | T | 1.22 (1.11-1.36) | 1.10E−04 | 0.480 | – | – | – | – | – | 32887889 |
| SNP . | Gene . | Chr . | Effect allele . | Discovery meta-analysis . | CRuCIAL cohort . | Overall meta-analysis . | References (PMID) . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (N = 724 567 healthy controls; 4272 CLL cases) . | (N = 1898 healthy controls; 1200 CLL cases) . | (N = 726 465 healthy controls; 5472 CLL cases) . | ||||||||||
| OR (95% CI) . | P value . | PHet . | OR (95% CI) . | P value . | OR (95% CI) . | P value . | PHet . | |||||
| rs59952010 | ARSB | 5 | T | 1.13 (1.06-1.19) | 6.29E−05 | 0.831 | – | – | – | – | – | 26956414 |
| rs210143 | BAK1 | 6 | C | 1.20 (1.13-1.27) | 3.39E−09 | 0.083 | – | – | – | – | – | 22700719; 24292274; 23770605; 28165464 |
| rs4987852 | BCL2 | 18 | C | 1.38 (1.26-1.51) | 5.40E−12 | 0.148 | – | – | – | – | – | 23770605 |
| rs4987856 | BCL2 | 18 | T | 0.72 (0.66-0.80) | 7.35E−11 | 0.518 | – | – | – | – | – | 26956414; 23770605 |
| rs1026825 | BCL2 | 18 | G | 1.12 (1.06-1.18) | 6.62E−05 | 0.672 | 1.06 (0.94-1.19) | .353 | 1.11 (1.06-1.16) | 1.75E−05 | 0.698 | – |
| rs11152374 | BCL2 | 18 | A | 1.12 (1.05-1.20) | 5.42E−04 | 0.377 | 0.97 (0.84-1.13) | .716 | 1.10 (1.04-1.16) | 1.13E−03 | 0.193 | – |
| rs11839271 | LPAR6, RB1 | 13 | T | 0.90 (0.85-0.96) | 4.34E−04 | 0.991 | 1.13 (0.96-1.33)∗ | .131 | 0.92 (0.88-0.97) | 1.63E−03 | 0.268 | – |
| rs12457371 | BCL2 | 18 | G | 0.88 (0.83-0.93) | 2.77E−05 | 0.988 | 0.92 (0.78-1.08) | .294 | 0.89 (0.84-0.93) | 3.69E−06 | 0.989 | – |
| rs143052840 | PRKCD | 3 | A | 1.26 (1.11-1.42) | 1.80E−04 | 0.339 | 0.82 (0.62-1.00)∗ | .152 | 1.18 (1.06-1.31) | 1.59E−03 | 0.027 | – |
| rs3731204 | CDKN2A | 9 | C | 0.78 (0.72-0.85) | 1.03E−09 | 0.972 | 0.80 (0.67-0.94) | 8.72E−03 | 0.78 (0.73-0.84) | 1.57E−12 | 0.982 | – |
| rs4940571 | BCL2 | 18 | G | 1.18 (1.08-1.29) | 3.05E−04 | 0.969 | 1.40 (1.15-1.71) | 8.66E−04 | 1.21 (1.12-1.31) | 3.25E−06 | 0.445 | – |
| rs1926194 | FAS | 10 | A | 1.29 (1.23-1.36) | 4.73E−21 | 0.145 | – | – | – | – | – | 24292274; 26956414; 28165464 |
| rs7584971 | ITGA6 | 2 | A | 1.17 (1.07-1.29) | 6.07E−04 | 0.578 | – | – | – | – | – | 32887889 |
| rs4947976 | EGFR | 7 | A | 1.15 (1.07-1.24) | 1.15E−04 | 0.780 | 1.02 (0.91-1.14)† | .723 | 1.11 (1.05-1.17) | 4.04E−04 | 0.360 | – |
| rs6829366 | NAF1 | 4 | T | 1.12 (1.05-1.20) | 4.26E−04 | 0.022 | 1.14 (0.98-1.31) | .087 | 1.12 (1.06-1.19) | 5.73E−05 | 0.024 | – |
| rs6910366 | TFEB | 6 | G | 0.86 (0.80-0.93) | 8.28E−05 | 0.850 | 1.07 (0.85-1.33)∗ | .574 | 0.87 (0.82-0.93) | 8.74E−05 | 0.474 | – |
| rs7236090 | BCL2 | 18 | C | 1.11 (1.05-1.17) | 1.92E−04 | 0.896 | 0.99 (0.88-1.12) | .912 | 1.10 (1.04-1.15) | 1.83E−04 | 0.746 | – |
| rs2645488 | VMP1 | 17 | G | 1.11 (1.04-1.18) | 7.71E−04 | 0.043 | – | – | – | – | – | 31407831 |
| rs17885803 | WRAP53, TP53 | 17 | T | 1.22 (1.11-1.36) | 1.10E−04 | 0.480 | – | – | – | – | – | 32887889 |
Estimates calculated according to a log-additive model of inheritance and adjusted for age and sex. Meta-analysis was performed assuming a fixed-effect model using METAL software. P < 2.63E−05 in bold.
Chr, Chromosome; PHet, P value for heterogeneity.
Association estimates was calculated in a subset of 1 055 healthy controls and 1 024 CLL cases from the CRuCIAL cohort.
Authors report the effect found for the rs12718945 (an SNP in complete linkage disequilibrium with the rs4947976, r2 = 0.996).