Highest ranked SNPs associated with methotrexate clearance in a meta-analysis (typed in 1279 COG patients, typed or imputed in 699 SJ patients)
| rsID . | Meta P . | A/B alleles . | Gene . | COG P . | COG effect size . | COG source . | COG B allele freq . | SJ P . | SJ effect size . | SJ source . | SJ B allele freq . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| rs11045879 | 3.13 × 10−19 | T/C | SLCO1B1 | 8.31 × 10−10 | −11.69 | SNPCHIP | 0.17 | 6.23 × 10−11 | −11.27 | SNPCHIP | 0.16 |
| rs4149056 | 5.72 × 10−19 | T/C | SLCO1B1 | 2.01 × 10−10 | −13.29 | SNPCHIP | 0.14 | 4.90 × 10−10 | −12.00 | GoldenGate | 0.12 |
| rs4149081 | 9.74 × 10−19 | G/A | SLCO1B1 | 1.58 × 10−10 | −12.19 | SNPCHIP | 0.18 | 1.05 × 10−9 | −10.61 | SNPCHIP | 0.16 |
| rs11045813 | 4.04 × 10−13 | A/G | SLCO1B1 | 2.95 × 10−7 | −12.89 | GoldenGate | 0.88 | 2.85 × 10−7 | −9.65 | GoldenGate | 0.87 |
| rs11045818 | 1.69 × 10−12 | A/G | SLCO1B1 | 1.35 × 10−6 | −11.66 | SNPCHIP | 0.88 | 2.63 × 10−7 | −9.88 | SNPCHIP | 0.87 |
| rs11045872 | 2.42 × 10−12 | A/G | SLCO1B1 | 3.77 × 10−7 | 11.49 | SNPCHIP | 0.15 | 1.36 × 10−6 | 8.70 | SNPCHIP | 0.15 |
| rs11045821 | 5.59 × 10−12 | G/A | SLCO1B1 | 3.33 × 10−8 | 13.49 | SNPCHIP | 0.13 | 2.44 × 10−5 | 8.46 | Imputed | 0.14 |
| rs11045870 | 3.81 × 10−11 | A/G | SLCO1B1 | 9.17 × 10−6 | −10.51 | GoldenGate | 0.86 | 8.94 × 10−7 | -8.74 | GoldenGate | 0.85 |
| rs10841753 | 5.31 × 10−11 | T/C | SLCO1B1 | 6.32 × 10−6 | 8.83 | SNPCHIP | 0.21 | 1.89 × 10−6 | 7.87 | SNPCHIP | 0.18 |
| rs11045892 | 6.60 × 10−11 | A/G | SLCO1B1 | 3.27 × 10−5 | 10.64 | GoldenGate | 0.14 | 3.76 × 10−7 | 8.98 | GoldenGate | 0.15 |
| rs11045825 | 7.80 × 10−11 | T/C | SLCO1B1 | 9.10 × 10−8 | 12.94 | SNPCHIP | 0.13 | 1.16 × 10−4 | 8.12 | Imputed | 0.16 |
| rs2169969 | 1.67 × 10−10 | A/G | SLCO1B1 | 4.35 × 10−7 | 11.75 | SNPCHIP | 0.15 | 6.84 × 10−5 | 8.23 | Imputed | 0.17 |
| rs16923647 | 7.64 × 10−10 | T/C | SLCO1A2 | 1.31 × 10−4 | 8.98 | SNPCHIP | 0.88 | 1.09 × 10−6 | 10.18 | SNPCHIP | 0.90 |
| rsID . | Meta P . | A/B alleles . | Gene . | COG P . | COG effect size . | COG source . | COG B allele freq . | SJ P . | SJ effect size . | SJ source . | SJ B allele freq . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| rs11045879 | 3.13 × 10−19 | T/C | SLCO1B1 | 8.31 × 10−10 | −11.69 | SNPCHIP | 0.17 | 6.23 × 10−11 | −11.27 | SNPCHIP | 0.16 |
| rs4149056 | 5.72 × 10−19 | T/C | SLCO1B1 | 2.01 × 10−10 | −13.29 | SNPCHIP | 0.14 | 4.90 × 10−10 | −12.00 | GoldenGate | 0.12 |
| rs4149081 | 9.74 × 10−19 | G/A | SLCO1B1 | 1.58 × 10−10 | −12.19 | SNPCHIP | 0.18 | 1.05 × 10−9 | −10.61 | SNPCHIP | 0.16 |
| rs11045813 | 4.04 × 10−13 | A/G | SLCO1B1 | 2.95 × 10−7 | −12.89 | GoldenGate | 0.88 | 2.85 × 10−7 | −9.65 | GoldenGate | 0.87 |
| rs11045818 | 1.69 × 10−12 | A/G | SLCO1B1 | 1.35 × 10−6 | −11.66 | SNPCHIP | 0.88 | 2.63 × 10−7 | −9.88 | SNPCHIP | 0.87 |
| rs11045872 | 2.42 × 10−12 | A/G | SLCO1B1 | 3.77 × 10−7 | 11.49 | SNPCHIP | 0.15 | 1.36 × 10−6 | 8.70 | SNPCHIP | 0.15 |
| rs11045821 | 5.59 × 10−12 | G/A | SLCO1B1 | 3.33 × 10−8 | 13.49 | SNPCHIP | 0.13 | 2.44 × 10−5 | 8.46 | Imputed | 0.14 |
| rs11045870 | 3.81 × 10−11 | A/G | SLCO1B1 | 9.17 × 10−6 | −10.51 | GoldenGate | 0.86 | 8.94 × 10−7 | -8.74 | GoldenGate | 0.85 |
| rs10841753 | 5.31 × 10−11 | T/C | SLCO1B1 | 6.32 × 10−6 | 8.83 | SNPCHIP | 0.21 | 1.89 × 10−6 | 7.87 | SNPCHIP | 0.18 |
| rs11045892 | 6.60 × 10−11 | A/G | SLCO1B1 | 3.27 × 10−5 | 10.64 | GoldenGate | 0.14 | 3.76 × 10−7 | 8.98 | GoldenGate | 0.15 |
| rs11045825 | 7.80 × 10−11 | T/C | SLCO1B1 | 9.10 × 10−8 | 12.94 | SNPCHIP | 0.13 | 1.16 × 10−4 | 8.12 | Imputed | 0.16 |
| rs2169969 | 1.67 × 10−10 | A/G | SLCO1B1 | 4.35 × 10−7 | 11.75 | SNPCHIP | 0.15 | 6.84 × 10−5 | 8.23 | Imputed | 0.17 |
| rs16923647 | 7.64 × 10−10 | T/C | SLCO1A2 | 1.31 × 10−4 | 8.98 | SNPCHIP | 0.88 | 1.09 × 10−6 | 10.18 | SNPCHIP | 0.90 |
A/B alleles indicates first allele shown is A, second is B; COG B-allele freq, B-allele frequency in the COG cohort; COG effect size, the change in methotrexate clearance (mL/min/m2) with each copy of the B allele in COG cohort; COG P, P-value for COG cohort; COG source, source of SNP genotype data in COG cohort—SNPCHIP (Affymetrix SNP 6.0), GoldenGate (Illumina), or imputed (details in supplemental Methods); Meta P, combined P-values (Stouffer method) from 1279 COG and 699 SJ patients; rsID, dbSNP ID; SJ B allele freq, B-allele frequency in the St Jude cohort; SJ effect size: the change in methotrexate clearance (mL/min/m2) with each copy of the B allele in St Jude cohort; SJ P, P-value for St Jude cohort; SJ source, source of SNP genotype data in SJ cohort—SNPCHIP (Affymetrix 500K), GoldenGate (Illumina), or imputed (details in supplemental Methods); and SNP, single-nucleotide polymorphism.
All SNPs significantly related to methotrexate clearance (n = 103, typed and imputed) can be found in supplemental Table 3.