Table 2.
Association of circulating 25(OH)D concentrations with GC and other vitamin D-related genes in the GWAS and replication study cohorts
| SNPa | Risk allele (freq) | Chr | Locationb | Gene neighborhood | Population | P-valuec | Mean 25(OH)D levels (nmol/l) by genotype (copies of risk allele) |
β-valued | SEd | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1 | 2 | |||||||||
| GWASs | |||||||||||
| rs2282679 | C (0.26) | 4 | 72827247 | GC | Total | 4.1 × 10−22 | −0.36 | 0.05 | |||
| ATBC | 1.5 × 10−8 | 42.1 | 37.2 | 35.2 | −0.38 | 0.07 | |||||
| CPS-II | 0.09 | 60.1 | 57.4 | 46.0 | −0.31 | 0.18 | |||||
| CLUE II | 2.2 × 10−3 | 67.5 | 58.4 | 44.3 | −0.69 | 0.22 | |||||
| PLCO | 5.8 × 10−13 | 61.5 | 55.3 | 53.4 | −0.37 | 0.05 | |||||
| NHS-CGEMS | 1.2 × 10−7 | 86.8 | 77.3 | 72.5 | −0.46 | 0.09 | |||||
| NHS-T2D | 9.5 × 10−4 | 58.8 | 55.8 | 48.8 | −0.24 | 0.07 | |||||
| Replication studies | Total | 5.4 × 10−21 | −0.41 | 0.04 | |||||||
| NHS-Polyps | 3.4 × 10−5 | 70.5 | 65.5 | 57.5 | −0.35 | 0.09 | |||||
| NHS-CRC | 2.2 × 10−6 | 71.5 | 67.3 | 56.3 | −0.42 | 0.09 | |||||
| HPFS | 3.1 × 10−13 | 65.5 | 56.8 | 53.5 | −0.44 | 0.06 | |||||
| Combined meta-analysis | 1.8 × 10−49 | −0.38 | 0.03 | ||||||||
| GWASs | |||||||||||
| rs3829251 | A (0.19) | 11 | 70872207 | NADSYN1 | Total | 8.8 × 10−7 | −0.17 | 0.04 | |||
| ATBC | 2.0 × 10−2 | 41.4 | 38.8 | 39.4 | −0.14 | 0.06 | |||||
| CPS-II | 0.75 | 61.1 | 64.9 | 61.0 | 0.07 | 0.21 | |||||
| CLUE II | 0.60 | 56.2 | 61.7 | 46.8 | 0.16 | 0.30 | |||||
| PLCO | 3.5 × 10−4 | 59.3 | 56.2 | 53.0 | −0.22 | 0.06 | |||||
| NHS-CGEMS | 9.2 × 10−3 | 83.3 | 77.8 | 81.3 | −0.28 | 0.11 | |||||
| NHS-T2D | 0.39 | 57.3 | 55.3 | 55.8 | −0.08 | 0.09 | |||||
| Replication studies | |||||||||||
| rs11234027e | A (0.16) | 70911755 | Total | 1.0 × 10−3 | −0.19 | 0.06 | |||||
| NHS-Polyps | 0.30 | 68.3 | 66.5 | 61.8 | −0.11 | 0.10 | |||||
| NHS-CRC | 0.16 | 69.0 | 67.3 | 51.8 | −0.17 | 0.12 | |||||
| HPFS | 1.7 × 10−3 | 62.0 | 57.3 | 57.5 | −0.25 | 0.08 | |||||
| Combined meta-analysis | 3.4 × 10−9 | −0.18 | 0.03 | ||||||||
| GWASs | |||||||||||
| rs6599638 | G (0.49) | 10 | 124694139 | C10orf88 | Total | 3.3 × 10−7 | −0.14 | 0.03 | |||
| ATBC | 5.0 × 10−4 | 41.8 | 39.6 | 39.5 | −0.19 | 0.06 | |||||
| CPS-II | 0.95 | 57.3 | 58.4 | 56.8 | −0.01 | 0.16 | |||||
| CLUE II | 0.11 | 65.6 | 61.8 | 58.0 | −0.33 | 0.20 | |||||
| PLCO | 1.3 × 10−2 | 60.3 | 57.8 | 57.6 | −0.11 | 0.05 | |||||
| NHS-CGEMS | 2.2 × 10−3 | 83.3 | 83.0 | 77.5 | −0.24 | 0.08 | |||||
| NHS-T2D | 0.12 | 58.5 | 56.0 | 55.5 | −0.10 | 0.07 | |||||
| Replication Studies | Total | 9.3 × 10−1 | 0.00 | 0.04 | |||||||
| NHS-Polyps | 0.70 | 68.3 | 67.3 | 66.5 | −0.03 | 0.07 | |||||
| NHS-CRC | 0.66 | 66.5 | 70.0 | 66.8 | −0.04 | 0.09 | |||||
| HPFS | 0.55 | 60.5 | 60.3 | 61.3 | 0.03 | 0.06 | |||||
| Combined meta-analysis | 2.4 × 10−5 | −0.09 | 0.04 | ||||||||
| GWASs | |||||||||||
| rs2060793 | A (0.41) | 11 | 14866810 | CYP2R1 | Total | 1.4 × 10−5 | 0.12 | 0.03 | |||
| ATBC | 0.28 | 39.5 | 40.7 | 40.1 | 0.06 | 0.06 | |||||
| CPS-II | 0.78 | 57.9 | 55.8 | 63.6 | 0.05 | 0.19 | |||||
| CLUE II | 0.92 | 62.1 | 57.7 | 71.1 | −0.03 | 0.25 | |||||
| PLCO | 0.15 | 57.1 | 59.1 | 58.6 | 0.07 | 0.05 | |||||
| NHS-CGEMS | 3.5 × 10−4 | 77.0 | 83.3 | 80.5 | 0.28 | 0.08 | |||||
| NHS-T2D | 8.9 × 10−4 | 53.8 | 58.0 | 59.3 | 0.22 | 0.07 | |||||
| Replication studies | |||||||||||
| rs1993116e | A (0.39) | 14866810 | Total | 1.6 × 10−17 | 0.34 | 0.04 | |||||
| NHS-Polyps | 6.2 × 10−9 | 62.5 | 68.8 | 75.0 | 0.39 | 0.07 | |||||
| NHS-CRC | 5.2 × 10−4 | 65.5 | 68.8 | 73.8 | 0.29 | 0.08 | |||||
| HPFS | 1.6 × 10−8 | 56.0 | 62.3 | 67.0 | 0.33 | 0.06 | |||||
| Combined meta-analysis | 2.9 × 10−17 | 0.25 | 0.05 | ||||||||
P-values for heterogeneity were >0.05, except for rs2060793 (P = 0.01).
aSNP identifier based on NCBI dbSNP.
bChromosomal location based on NCBI Human Genome Build 35 coordinates.
cThe result of 1 df test based on linear regression, using an additive model, after square-root transformation of 25(OH)D levels—adjusted for age, vitamin D assay batch, study, case–control status, sex, body mass index, season of blood collection, vitamin D supplement intake, dietary vitamin D intake, region/latitude and chosen eigenvectors to control population stratification. The pooled P-value is based on the combined Wald statistics weighted by the square-root of the corresponding sample size.
dSE: standard error; the regression β and standard error were based on square-root scale. The pooled β and standard error summary calculated based on the random-effect model.
er2 = 1 in the HapMap CEU panel with the SNP from the initial GWAS.