Meta-analysis of the autophagy-related risk variants for CLL in the discovery cohorts
| SNP . | Gene . | Chr . | Effect allele . | InterLymph cohort . | UK Biobank . | FinnGen Risteys 10 . | Discovery meta-analysis . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (N = 3099 CLL cases and 7666 healthy controls) . | (N = 505 CLL cases and 402 712 healthy controls) . | (N = 668 CLL cases 314 189 healthy controls) . | (N = 4272 CLL cases and 724 567 healthy controls) . | |||||||||
| OR (95% CI) . | P value . | OR (95% CI) . | P value . | OR (95% CI) . | P value . | OR (95% CI) . | P value . | phet . | ||||
| rs59952010 | ARSB | 5 | T | 1.13 (1.06-1.21) | 2.16 × 10−4 | 1.17 (1.03-1.34) | .020 | 1.05 (0.93-1.19) | .418 | 1.13 (1.06-1.19) | 6.29 × 10−5 | 0.831 |
| rs210143 | BAK1 | 6 | C | 1.21 (1.13-1.30) | 9.52 × 10–8 | 1.08 (0.94-1.24) | .260 | 1.29 (1.13-1.48) | 1.65 × 10−4 | 1.20 (1.13-1.27) | 3.39 × 10−9 | 0.083 |
| rs4987852 | BCL2 | 18 | C | 1.43 (1.28-1.61) | 1.61 × 10−9 | 1.06 (0.84-1.34) | .640 | 1.47 (1.27-1.72) | 5.30 × 10−7 | 1.38 (1.26-1.51) | 5.40 × 10−12 | 0.148 |
| rs4987856 | BCL2 | 18 | T | 0.69 (0.66-0.77) | 3.55 × 10−11 | 0.75 (0.60-0.93) | 7.50 × 10−3 | 0.87 (0.68-1.11) | .249 | 0.72 (0.66-0.80) | 7.35 × 10−11 | 0.518 |
| rs1026825 | BCL2 | 18 | G | 1.09 (1.03-1.16) | 4.08 × 10−3 | 1.21 (1.07-1.37) | 3.50 × 10−3 | 1.10 (0.99-1.23) | .078 | 1.12 (1.06-1.18) | 6.62 × 10−5 | 0.672 |
| rs11152374 | BCL2 | 18 | A | 1.12 (1.04-1.21) | 3.72 × 10−3 | 1.15 (0.99-1.34) | .078 | 1.09 (0.97-1.24) | .159 | 1.12 (1.05-1.20) | 5.42 × 10−4 | 0.377 |
| rs4940571 | BCL2 | 18 | G | 1.20 (1.08-1.34) | 9.11 × 10−4 | 1.19 (0.96-1.47) | .120 | 1.13 (0.96-1.34) | .143 | 1.18 (1.08-1.29) | 3.05 × 10−4 | 0.969 |
| rs7236090 | BCL2 | 18 | C | 1.10 (1.03-1.17) | 3.84 × 10−3 | 1.16 (1.02-1.32) | .017 | 1.09 (0.98-1.22) | .121 | 1.11 (1.05-1.17) | 1.92 × 10−4 | 0.896 |
| rs12457371 | BCL2 | 18 | G | 0.89 (0.83-0.94) | 3.66 × 10−4 | 0.91 (0.79-1.05) | .210 | 0.86 (0.77-0.97) | .010 | 0.88 (0.83-0.93) | 2.77 × 10−5 | 0.988 |
| rs3731204 | CDKN2A | 9 | C | 0.79 (0.72-0.87) | 4.42 × 10−7 | 0.76 (0.64-0.91) | 2.90 × 10−3 | 0.76 (0.63-0.91) | 3.41 × 10−3 | 0.78 (0.72-0.85) | 1.03 × 10−9 | 0.972 |
| rs4947976 | EGFR | 7 | A | 1.03 (0.97-1.09) | .383 | 1.22 (1.08-1.38) | 2.40 × 10−3 | 1.12 (1.01-1.25) | .039 | 1.15 (1.07-1.24) | 1.15 × 10−4 | 0.780 |
| rs1926194 | FAS | 10 | A | 1.27 (1.19-1.35) | 1.15 × 10−13 | 1.32 (1.16-1.50) | 1.70 × 10−5 | 1.34 (1.20-1.50) | 1.61 × 10−7 | 1.29 (1.23-1.36) | 4.73 × 10−21 | 0.145 |
| rs7584971 | ITGA6 | 2 | A | 1.01 (0.93-1.11) | .800 | 1.20 (1.00-1.44) | .050 | 1.22 (1.08-1.38) | 1.14 × 10−3 | 1.17 (1.07-1.29) | 6.07 × 10−4 | 0.578 |
| rs11839271 | LPAR6, RB1 | 13 | T | 0.90 (0.84-0.96) | 2.28 × 10−3 | 0.92 (0.80-1.05) | .220 | 0.89 (0.79-1.00) | .052 | 0.90 (0.85-0.96) | 4.34 × 10−4 | 0.991 |
| rs6829366 | NAF1 | 4 | T | 1.13 (1.05-1.21) | 1.49 × 10−3 | 1.16 (1.00-1.35) | .055 | 1.05 (0.91-1.21) | .478 | 1.12 (1.05-1.20) | 4.26 × 10−4 | 0.022 |
| rs143052840 | PRKCD | 3 | A | 1.25 (1.09-1.44) | 1.14 × 10−3 | 1.54 (1.19-1.98) | 7.30 × 10−4 | 0.96 (0.72-1.29) | .786 | 1.26 (1.11-1.42) | 1.80 × 10−4 | 0.339 |
| rs6910366 | TFEB | 6 | G | 0.83 (0.76-0.91) | 5.11 × 10−5 | 0.84 (0.70-1.02) | .068 | 0.94 (0.81-1.09) | .429 | 0.86 (0.80-0.93) | 8.28 × 10−5 | 0.850 |
| rs2645488 | VMP1 | 17 | G | 1.14 (1.07-1.22) | 1.60 × 10−4 | 1.19 (1.03-1.36) | .017 | 0.95 (0.85-1.07) | .403 | 1.11 (1.04-1.18) | 7.71 × 10−4 | 0.043 |
| rs17885803 | WRAP53, TP53 | 17 | T | 1.27 (1.11-1.44) | 2.93 × 10−4 | 1.36 (1.06-1.76) | .017 | 1.10 (0.93-1.31) | .265 | 1.22 (1.11-1.36) | 1.10 × 10−4 | 0.480 |
| SNP . | Gene . | Chr . | Effect allele . | InterLymph cohort . | UK Biobank . | FinnGen Risteys 10 . | Discovery meta-analysis . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (N = 3099 CLL cases and 7666 healthy controls) . | (N = 505 CLL cases and 402 712 healthy controls) . | (N = 668 CLL cases 314 189 healthy controls) . | (N = 4272 CLL cases and 724 567 healthy controls) . | |||||||||
| OR (95% CI) . | P value . | OR (95% CI) . | P value . | OR (95% CI) . | P value . | OR (95% CI) . | P value . | phet . | ||||
| rs59952010 | ARSB | 5 | T | 1.13 (1.06-1.21) | 2.16 × 10−4 | 1.17 (1.03-1.34) | .020 | 1.05 (0.93-1.19) | .418 | 1.13 (1.06-1.19) | 6.29 × 10−5 | 0.831 |
| rs210143 | BAK1 | 6 | C | 1.21 (1.13-1.30) | 9.52 × 10–8 | 1.08 (0.94-1.24) | .260 | 1.29 (1.13-1.48) | 1.65 × 10−4 | 1.20 (1.13-1.27) | 3.39 × 10−9 | 0.083 |
| rs4987852 | BCL2 | 18 | C | 1.43 (1.28-1.61) | 1.61 × 10−9 | 1.06 (0.84-1.34) | .640 | 1.47 (1.27-1.72) | 5.30 × 10−7 | 1.38 (1.26-1.51) | 5.40 × 10−12 | 0.148 |
| rs4987856 | BCL2 | 18 | T | 0.69 (0.66-0.77) | 3.55 × 10−11 | 0.75 (0.60-0.93) | 7.50 × 10−3 | 0.87 (0.68-1.11) | .249 | 0.72 (0.66-0.80) | 7.35 × 10−11 | 0.518 |
| rs1026825 | BCL2 | 18 | G | 1.09 (1.03-1.16) | 4.08 × 10−3 | 1.21 (1.07-1.37) | 3.50 × 10−3 | 1.10 (0.99-1.23) | .078 | 1.12 (1.06-1.18) | 6.62 × 10−5 | 0.672 |
| rs11152374 | BCL2 | 18 | A | 1.12 (1.04-1.21) | 3.72 × 10−3 | 1.15 (0.99-1.34) | .078 | 1.09 (0.97-1.24) | .159 | 1.12 (1.05-1.20) | 5.42 × 10−4 | 0.377 |
| rs4940571 | BCL2 | 18 | G | 1.20 (1.08-1.34) | 9.11 × 10−4 | 1.19 (0.96-1.47) | .120 | 1.13 (0.96-1.34) | .143 | 1.18 (1.08-1.29) | 3.05 × 10−4 | 0.969 |
| rs7236090 | BCL2 | 18 | C | 1.10 (1.03-1.17) | 3.84 × 10−3 | 1.16 (1.02-1.32) | .017 | 1.09 (0.98-1.22) | .121 | 1.11 (1.05-1.17) | 1.92 × 10−4 | 0.896 |
| rs12457371 | BCL2 | 18 | G | 0.89 (0.83-0.94) | 3.66 × 10−4 | 0.91 (0.79-1.05) | .210 | 0.86 (0.77-0.97) | .010 | 0.88 (0.83-0.93) | 2.77 × 10−5 | 0.988 |
| rs3731204 | CDKN2A | 9 | C | 0.79 (0.72-0.87) | 4.42 × 10−7 | 0.76 (0.64-0.91) | 2.90 × 10−3 | 0.76 (0.63-0.91) | 3.41 × 10−3 | 0.78 (0.72-0.85) | 1.03 × 10−9 | 0.972 |
| rs4947976 | EGFR | 7 | A | 1.03 (0.97-1.09) | .383 | 1.22 (1.08-1.38) | 2.40 × 10−3 | 1.12 (1.01-1.25) | .039 | 1.15 (1.07-1.24) | 1.15 × 10−4 | 0.780 |
| rs1926194 | FAS | 10 | A | 1.27 (1.19-1.35) | 1.15 × 10−13 | 1.32 (1.16-1.50) | 1.70 × 10−5 | 1.34 (1.20-1.50) | 1.61 × 10−7 | 1.29 (1.23-1.36) | 4.73 × 10−21 | 0.145 |
| rs7584971 | ITGA6 | 2 | A | 1.01 (0.93-1.11) | .800 | 1.20 (1.00-1.44) | .050 | 1.22 (1.08-1.38) | 1.14 × 10−3 | 1.17 (1.07-1.29) | 6.07 × 10−4 | 0.578 |
| rs11839271 | LPAR6, RB1 | 13 | T | 0.90 (0.84-0.96) | 2.28 × 10−3 | 0.92 (0.80-1.05) | .220 | 0.89 (0.79-1.00) | .052 | 0.90 (0.85-0.96) | 4.34 × 10−4 | 0.991 |
| rs6829366 | NAF1 | 4 | T | 1.13 (1.05-1.21) | 1.49 × 10−3 | 1.16 (1.00-1.35) | .055 | 1.05 (0.91-1.21) | .478 | 1.12 (1.05-1.20) | 4.26 × 10−4 | 0.022 |
| rs143052840 | PRKCD | 3 | A | 1.25 (1.09-1.44) | 1.14 × 10−3 | 1.54 (1.19-1.98) | 7.30 × 10−4 | 0.96 (0.72-1.29) | .786 | 1.26 (1.11-1.42) | 1.80 × 10−4 | 0.339 |
| rs6910366 | TFEB | 6 | G | 0.83 (0.76-0.91) | 5.11 × 10−5 | 0.84 (0.70-1.02) | .068 | 0.94 (0.81-1.09) | .429 | 0.86 (0.80-0.93) | 8.28 × 10−5 | 0.850 |
| rs2645488 | VMP1 | 17 | G | 1.14 (1.07-1.22) | 1.60 × 10−4 | 1.19 (1.03-1.36) | .017 | 0.95 (0.85-1.07) | .403 | 1.11 (1.04-1.18) | 7.71 × 10−4 | 0.043 |
| rs17885803 | WRAP53, TP53 | 17 | T | 1.27 (1.11-1.44) | 2.93 × 10−4 | 1.36 (1.06-1.76) | .017 | 1.10 (0.93-1.31) | .265 | 1.22 (1.11-1.36) | 1.10 × 10−4 | 0.480 |
Estimates calculated according to a log-additive model of inheritance and adjusted for age, sex and country of origin. The meta-analysis was performed assuming a fixed-effect model using METAL. P < 2.63E−5 in bold.
Chr, chromosome.