Single nucleotide polymorphisms (SNPs) associated with gout and its subtypes at a genome-wide level of significance in the Japanese population
| SNP* | Chr. | GWAS¶ | Replication study** | Meta-analysis†† | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Position | Frequency of A1 | OR (95% CI) | p Value | Frequency of A1 | OR (95% CI) | p Value | OR (95% CI) | p Value | Heterogeneity | ||||||||
| Gout types | (bp)† | Gene‡ | A1/A2§ | Cases | Controls | Cases | Controls | Cochran's Q | I2 (%) | ||||||||
| All gout | rs1260326 | 2 | 27730940 | GCKR | T/C | 0.616 | 0.535 | 1.39 (1.23 to 1.57) | 1.34×10−7 | 0.611 | 0.557 | 1.25 (1.12 to 1.39) | 6.10×10−5 | 1.31 (1.21 to 1.42) | 7.19×10−11 | 0.20 | 38.2 |
| rs1014290 | 4 | 10001861 | SLC2A9 | T/C | 0.678 | 0.564 | 1.63 (1.44 to 1.85) | 1.75×10−14 | 0.673 | 0.576 | 1.51 (1.35 to 1.69) | 2.97×10−13 | 1.57 (1.44 to 1.70) | 6.50×10−26 | 0.39 | 0.0 | |
| rs3114020 | 4 | 89083666 | ABCG2 | C/T | 0.842 | 0.724 | 2.03 (1.75 to 2.37) | 1.17×10−20 | 0.844 | 0.752 | 1.78 (1.55 to 2.04) | 7.74×10−17 | 1.89 (1.71 to 2.09) | 8.66×10−35 | 0.20 | 38.9 | |
| rs1165176 | 6 | 25830298 | SLC17A1 | G/A | 0.874 | 0.834 | 1.38 (1.16 to 1.64) | 2.89×10−4 | 0.872 | 0.824 | 1.46 (1.25 to 1.69) | 1.08×10−6 | 1.42 (1.27 to 1.59) | 1.47×10−9 | 0.63 | 0.0 | |
| rs11758351 | 6 | 26203910 | HIST1H2BF-HIST1H4E | G/T | 0.158 | 0.121 | 1.37 (1.15 to 1.63) | 4.22×10−4 | 0.158 | 0.116 | 1.43 (1.22 to 1.67) | 1.01×10−5 | 1.40 (1.25 to 1.57) | 1.63×10−8 | 0.72 | 0.0 | |
| rs2285340 | 11 | 64435906 | SLC22A12 | A/G | 0.228 | 0.174 | 1.40 (1.21 to 1.63) | 1.09×10−5 | 0.227 | 0.174 | 1.40 (1.22 to 1.61) | 9.96×10−7 | 1.40 (1.27 to 1.55) | 4.61×10−11 | 1.00 | 0.0 | |
| rs4073582 | 11 | 66050712 | CNIH-2 | C/T | 0.950 | 0.915 | 1.78 (1.39 to 2.29) | 4.32×10−6 | 0.943 | 0.920 | 1.44 (1.16 to 1.79) | 8.47×10−4 | 1.58 (1.34 to 1.86) | 3.56×10−8 | 0.21 | 36.1 | |
| rs4766566 | 12 | 111706877 | CUX2 | T/C | 0.735 | 0.633 | 1.60 (1.41 to 1.83) | 1.22×10−12 | 0.741 | 0.665 | 1.44 (1.28 to 1.62) | 2.07×10−9 | 1.51 (1.38 to 1.65) | 4.03×10−20 | 0.22 | 33.8 | |
| ROL gout | rs1260326 | 2 | 27730940 | GCKR | T/C | 0.611 | 0.535 | 1.36 (1.18 to 1.58) | 2.43×10−5 | 0.626 | 0.557 | 1.33 (1.16 to 1.53) | 6.12×10−5 | 1.35 (1.22 to 1.49) | 5.39×10−9 | 0.81 | 0.0 |
| rs3733589 | 4 | 9987324 | SLC2A9 | G/A | 0.662 | 0.570 | 1.48 (1.28 to 1.71) | 2.00×10−7 | 0.668 | 0.580 | 1.46 (1.26 to 1.68) | 2.05×10−7 | 1.47 (1.32 to 1.63) | 2.25×10−13 | 0.88 | 0.0 | |
| rs2728104 | 4 | 88973006 | ABCG2 | C/T | 0.505 | 0.346 | 1.93 (1.67 to 2.23) | 3.28×10−19 | 0.496 | 0.359 | 1.75 (1.53 to 2.01) | 1.56×10−15 | 1.84 (1.66 to 2.03) | 5.08×10−33 | 0.35 | 0.0 | |
| rs4766566 | 12 | 111706877 | CUX2 | T/C | 0.737 | 0.633 | 1.62 (1.39 to 1.90) | 8.42×10−10 | 0.757 | 0.665 | 1.57 (1.34 to 1.83) | 7.55×10−9 | 1.59 (1.43 to 1.78) | 8.14×10−17 | 0.76 | 0.0 | |
| RUE gout | rs780094 | 2 | 27741237 | GCKR | T/C | 0.633 | 0.543 | 1.45 (1.26 to 1.67) | 2.43×10−7 | 0.615 | 0.559 | 1.26 (1.10 to 1.44) | 6.47×10−4 | 1.35 (1.22 to 1.48) | 1.62×10−9 | 0.16 | 48.8 |
| rs1014290 | 4 | 10001861 | SLC2A9 | T/C | 0.699 | 0.564 | 1.80 (1.55 to 2.08) | 1.58×10−15 | 0.685 | 0.576 | 1.60 (1.39 to 1.84) | 1.72×10−11 | 1.69 (1.53 to 1.87) | 8.71×10−25 | 0.26 | 21.8 | |
| rs11733284 | 4 | 48028097 | NIPAL1 | A/G | 0.346 | 0.281 | 1.35 (1.17 to 1.57) | 6.48×10−5 | 0.342 | 0.280 | 1.34 (1.16 to 1.54) | 6.36×10−5 | 1.34 (1.21 to 1.49) | 1.13×10−8 | 0.91 | 0.0 | |
| rs1871744 | 4 | 89039629 | ABCG2 | T/C | 0.834 | 0.723 | 1.93 (1.62 to 2.29) | 3.85×10−14 | 0.824 | 0.733 | 1.71 (1.45 to 2.01) | 7.04×10−11 | 1.81 (1.60 to 2.04) | 2.49×10−22 | 0.33 | 0.0 | |
| rs7903456 | 10 | 88919319 | FAM35A | A/G | 0.303 | 0.248 | 1.32 (1.13 to 1.53) | 4.32×10−4 | 0.296 | 0.235 | 1.37 (1.18 to 1.59) | 3.09×10−5 | 1.34 (1.21 to 1.49) | 4.29×10−8 | 0.72 | 0.0 | |
| rs2285340 | 11 | 64435906 | SLC22A12 | A/G | 0.236 | 0.174 | 1.47 (1.25 to 1.74) | 8.04×10−6 | 0.228 | 0.174 | 1.41 (1.20 to 1.66) | 4.04×10−5 | 1.44 (1.28 to 1.62) | 8.79×10−10 | 0.72 | 0.0 | |
| rs4766566 | 12 | 111706877 | CUX2 | T/C | 0.738 | 0.633 | 1.63 (1.40 to 1.89) | 1.58×10−10 | 0.759 | 0.665 | 1.58 (1.36 to 1.83) | 9.51×10−10 | 1.60 (1.44 to 1.78) | 2.17×10−18 | 0.78 | 0.0 | |
*dbSNP rs number. SNPs having associations for all gout, ROL gout and RUE gout at the lowest p value in each locus by meta-analysis are shown in this table.
†SNP positions are based on NCBI human genome reference sequence build 37.4.
‡Five discovered loci are shown in bold.
§A1 is risk-associated allele and A2 is non-risk-associated allele.
¶945 cases for all gout, 560 cases for ROL gout, 619 cases for RUE gout with 1213 controls from Japanese male population.
**1396 cases for all gout, 618 cases for ROL gout, 696 cases for RUE gout with 1268 controls from Japanese male population.
††Meta-analysis of GWAS and replication samples.
Chr., chromosome; GWAS, genome-wide association study; ROL, renal overload; RUE, renal underexcretion; SNP, single nucleotide polymorphism.