Table 2. Three independent signals in the DEFA region. r 2=0 between rs9314614 and rs12716641.
| SNP | Risk allele | Risk allele | Multivariate analysis* | |||
|---|---|---|---|---|---|---|
| Risk/non-risk allele | frequency cases (%) | frequency controls (%) | P value | OR (95% CI) | P value | OR (95% CI) |
| rs2738058 | chr8:6821617 | |||||
| T/C | ||||||
| GWAS logistic | 73.0 | 66.6 | 5.75E−10 | 1.310 (1.203–1.427) | 2.06E−08 | 1.298 (1.185–1.422) |
| GWAS gemma | 1.51E−10 | |||||
| Validation 1 | 72.4 | 69.0 | 6.10E−05 | 1.181 (1.089–1.281) | 4.88E−03 | 1.131 (1.038–1.232) |
| Validation 2 Southern | 71.9 | 66.0 | 1.92E−06 | 1.327 (1.181–1.491) | 6.46E−05 | 1.284 (1.136–1.451) |
| Validation 2 Northern | 72.3 | 67.6 | 7.08E−05 | 1.245 (1.117–1.386) | 6.28E−04 | 1.219 (1.088–1.366) |
| Validation 3 Southern | 72.6 | 67.3 | 8.74E−05 | 1.303 (1.142–1.487) | 8.58E−04 | 1.263 (1.101–1.450) |
| Validation 3 Northern | 73.4 | 67.0 | 1.64E−04 | 1.354 (1.156–1.585) | 1.26E−03 | 1.310 (1.112–1.543) |
| All validation | 4.14E−19 | 1.253 (1.193–1.317) | 1.67E−17 | 1.226 (1.170–1.285) | ||
| Meta-analysis | I2=31%, Phet=0.400 | 2.31E−27 | 1.267 (1.214–1.323) | 1.15E−19 | 1.232 (1.178–1.289) | |
| rs9314614 | chr8:6697731 | |||||
| C/G | ||||||
| GWAS logistic | 39.7 | 36.0 | 3.54E−05 | 1.191 (1.097–1.295) | 2.85E−04 | 1.161 (1.071–1.258) |
| GWAS gemma | 6.20E−05 | |||||
| Validation 1 | 37.7 | 35.0 | 3.77E−03 | 1.121 (1.038–1.211) | 2.03E−03 | 1.130 (1.046–1.222) |
| Validation 2 Southern | 38.6 | 35.6 | 2.10E−02 | 1.135 (1.019–1.264) | 3.03E−02 | 1.127 (1.011–1.256) |
| Validation 2 Northern | 40.2 | 39.1 | 3.42E−01 | 1.051 (0.948–1.165) | 3.72E−01 | 1.048 (0.945–1.163) |
| Validation 3 Southern | 38.4 | 36.0 | 1.03E−01 | 1.108 (0.980–1.253) | 9.97E−02 | 1.109 (0.981–1.255) |
| Validation 3 Northern | 41.9 | 36.8 | 4.85E−03 | 1.234 (1.066–1.428) | 6.73E−03 | 1.225 (1.058–1.419) |
| All validation | 2.66E−06 | 1.118 (1.067–1.171) | 9.55E−08 | 1.121 (1.075–1.170) | ||
| Meta-analysis | I2=0%, Phet=0.442 | 9.48E−10 | 1.135 (1.090–1.182) | 4.25E−09 | 1.129 (1.084–1.176) | |
| rs12716641 | chr8:6898998 | |||||
| T/C | ||||||
| GWAS logistic | 78.0 | 74.3 | 7.80E−07 | 1.260 (1.150–1.381) | 4.40E−03 | 1.153 (1.045–1.272) |
| GWAS gemma | 1.79E−06 | |||||
| Validation 1 | 78.2 | 73.6 | 1.22E−08 | 1.287 (1.180–1.404) | 2.95E−06 | 1.244 (1.135–1.363) |
| Validation 2 Southern | 78.8 | 75.2 | 1.81E−03 | 1.219 (1.076–1.381) | 8.47E−02 | 1.122 (0.984–1.278) |
| Validation 2 Northern | 80.4 | 78.4 | 5.44E−02 | 1.129 (0.998–1.278) | 3.91E−01 | 1.058 (0.929–1.205) |
| Validation 3 Southern | 78.7 | 75.5 | 1.00E−02 | 1.204 (1.045–1.386) | 1.01E−01 | 1.131 (0.976–1.311) |
| Validation 3 Northern | 80.5 | 77.4 | 3.85E−02 | 1.207 (1.010–1.442) | 2.65E−01 | 1.112 (0.923–1.339) |
| All validation | 2.34E−13 | 1.224 (1.159–1.291) | 1.66E−08 | 1.157 (1.100–1.218) | ||
| Meta-analysis | I2=0%, Phet=0.432 | 1.13E−18 | 1.233 (1.177–1.292) | 9.53E−09 | 1.154 (1.099–1.212) | |
CI, confidence interval; GWAS, genome-wide association study; OR, odds ratio; SNP, single-nucleotide polymorphism.
Only rs2738058 is in LD (r2=0.71) with the reported SNP rs2738048.For the GWAS samples, only the result from logistic regression analyses (GWAS logistic) was used in the fixed-effects meta-analysis with the validation samples.
*Pairwise LD (r2) between rs2738058 and rs9314614=0.001, between rs12716641 and rs2738058=0.074. There is no LD between rs9314614 and rs12716641 (r2=0).