Table 4. Associations between candidate SNPs, season-standardized 25(OH)D levels, and the risks cardiovascular diseases.
|
25(OH)D levels by alleles
|
Risk of myocardial Infarction†
|
Risk of stroke†
|
Risk of CVD (composite)†
|
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---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SNP, locus* | Allele |
N subcohort
|
Mean 25(OH)D | P** | R2 | N cases | HR | 95% CI | P | N cases | HR | 95% CI | P | N cases | HR | 95% CI | P | |
rs1155563, | T/T | 1059 |
49.7 | 281 | Ref. | 243 | Ref. | 524 | Ref. | |||||||||
GC | T/C | 832 |
45.1 | 224 | 1.07 | (0.86-1.33) | 185 | 0.99 | (0.79-1.24) | 409 | 1.05 | (0.88-1.25) | ||||||
C/C | 164 |
42.4 | <0.01 | 2.1 | 36 | 0.80 | (0.53-1.21) | 0.73 | 32 | 0.90 | (0.59-1.37) | 0.69 | 68 | 0.84 | (0.60-1.18) | 0.72 | ||
rs2282679, | A/A | 1058 | 50.0 | 288 | Ref. | 249 | Ref. | 537 | Ref. | |||||||||
GC | A/C | 827 | 45.0 | 216 | 0.97 | (0.77-1.21) | 183 | 0.91 | (0.73-1.14) | 399 | 0.94 | (0.79-1.13) | ||||||
C/C | 166 | 40.3 | <0.01 | 3.0 | 38 | 0.85 | (0.57-1.27) | 0.48 | 31 | 0.85 | (0.56-1.31) | 0.32 | 69 | 0.85 | (0.61-1.19) | 0.31 | ||
rs3829251, | G/G | 1415 | 48.2 | 380 | Ref. | 314 | Ref. | 694 | Ref. | |||||||||
DHCR7/ | G/A | 594 | 45.1 | 150 | 1.04 | (0.83-1.31) | 140 | 1.15 | (0.91-1.45) | 290 | 1.09 | (0.90-1.31) | ||||||
NADSYN1 | A/A | 60 | 44.0 | <0.01 | 0.7 | 15 | 1.17 | (0.63-2.17) | 0.61 | 11 | 1.0 | (0.50-1.98) | 0.34 | 26 | 1.09 | (0.65-1.83) | 0.38 | |
rs12785878, | T/T | 1081 | 49.0 | 290 | Ref. | 241 | Ref. | 531 | Ref. | |||||||||
DHCR7/ | T/G | 806 | 46.2 | 210 | 1.04 | (0.84-1.29) | 181 | 1.05 | (0.84-1.31) | 391 | 1.06 | (0.89-1.27) | ||||||
NADSYN1 | G/G | 172 | 40.3 | <0.01 | 1.7 | 42 | 1.12 | (0.76-1.65) | 0.55 | 42 | 1.23 | (0.83-1.81) | 0.35 | 84 | 1.20 | (0.87-1.65) | 0.38 | |
rs6599638, | G/G | 555 | 46.3 | 135 | Ref. | 127 | Ref. | 262 | Ref. | |||||||||
C10orff88 | G/A | 1020 | 47.6 | 268 | 1.10 | (0.86-1.41) | 231 | 1.02 | (0.79-1.31) | 499 | 1.07 | (0.87-1.31) | ||||||
A/A | 488 | 47.1 | 1.0 | 0.0 | 141 | 1.14 | (0.85-1.52) | 0.36 | 106 | 0.92 | (0.68-1.23) | 0.56 | 247 | 1.05 | (0.83-1.33) | 0.70 | ||
rs10741657, | G/G | 768 | 46.2 | 208 | Ref. | 183 | Ref. | 391 | Ref. | |||||||||
CYP2R1 | G/A | 966 | 47.0 | 251 | 1.07 | (0.86-1.34) | 212 | 1.03 | (0.82-1.30) | 463 | 1.06 | (0.88-1.28) | ||||||
A/A | 317 | 49.2 | 0.10 | 0.3 | 87 | 0.94 | (0.69-1.28) | 0.87 | 66 | 0.81 | (0.60-1.24) | 0.33 | 153 | 0.90 | (0.69-1.16) | 0.62 | ||
rs10877012, | G/G | 919 | 48.1 | 243 | Ref. | 213 | Ref. | 456 | Ref. | |||||||||
CYP27B1 | T/G | 910 | 46.7 | 251 | 1.10 | (0.89-1.37) | 203 | 1.00 | (0.80-1.25) | 454 | 1.11 | (0.89-1.40) | ||||||
T/T | 238 | 45.3 | 0.16 | 0.3 | 49 | 0.79 | (0.55-1.13) | 0.59 | 47 | 0.86 | (0.59-1.23) | 0.53 | 96 | 1.07 | (0.86-1.35) | 0.38 | ||
rs6013897, | T/T | 1315 | 47.7 | 337 | Ref. | 276 | Ref. | 613 | Ref. | |||||||||
CYP24A1 | T/A | 680 | 46.3 | 185 | 1.07 | (0.86-1.34) | 164 | 1.16 | (0.92-1.45) | 349 | 1.09 | (0.90-1.31) | ||||||
A/A | 67 | 46.5 | 0.99 | 0.1 | 27 | 1.50 | (0.90-2.52) | 0.18 | 22 | 1.54 | (0.90-2.63) | 0.07 | 49 | 1.48 | (0.96-2.30) | 0.07 | ||
SNP Score‡ | Risk alleles | |||||||||||||||||
0 | 546 | 52.4 | 159 | Ref. | 127 | Ref. | 286 | Ref. | ||||||||||
1 | 865 | 47.3 | 210 | 0.88 | (0.69-1.13) | 190 | 1.00 | (0.77-1.29) | 400 | 0.94 | (0.76-1.13) | |||||||
2 | 462 | 43.9 | 123 | 0.93 | (0.70-1.25) | 113 | 1.05 | (0.78-1.42) | 236 | 1.01 | (0.79-1.29) | |||||||
≥3 | 161 | 38.9 | <0.01 | 4.4 | 41 | 1.07 | (0.71-1.62) | 1.0 | 30 | 0.90 | (0.57-1.42) | 0.95 | 71 | 1.00 | (0.71-1.42) | 0.90 |
Percentages of missing values for single SNPs: rs1155563: 3.5%, rs2282679:3.4%, rs3829251:2.8%, rs6013897: 2.9%, rs6599638:3.0%, rs10741657:3.4%, rs10877012:3.0%, and rs12785878:3.3%;
P for linear trend calculated by ANCOVA within Generalized Linear Models modeling the number of risk alleles as continuous score, adjusted for age, sex and study center; Initial p values were multiplied by 8 to account for the number of tested SNPs;
Calculated by Cox regression analyses stratified by age and center, and adjusted for sex; P for linear trend calculated modeling the number of risk alleles as continuous score; P values from Cox regressions were not corrected for multiple testing because all associations were non-significant;
Consisting of rs2282679 and rs12785878; rs1155563 and rs2282679 in the GC locus, as well as rs3829251 and rs12785878 in the DHCR7/NADSYN1 loci were in strong linkage disequilibrium (R2>0.8);
No deviation from Hardy-Weinberg-Equilibrium was detected for any of the SNPs