Table 3.
Associations of the EDIP score with metabolites in the discovery (WHI-HT) and replication (WHI-OS) datasets1,2,3,4
| Associations in WHI-HT (discovery, n=1109) | Associations in WHI-OS (replication, n=810) | ||||
|---|---|---|---|---|---|
| Metabolite | HMDB # | Beta estimate (95%CI) | FDR –adjusted P-value | Beta estimate (95%CI) | FDR-adjusted P-value |
| Trigonelline | HMDB0000875 | −1.32 (−1.59, −1.05) | 8.88 E-19 | −1.11 (−1.44, −0.78) | 2.75 E-10 |
| Caffeine | HMDB0001847 | −0.48 (−0.74, −0.22) | 0.007 | −0.86 (−1.23, −0.49) | 1.34 E-05 |
| 5-acetylamino-6-amino-3-methyluracil | HMDB0004400 | −0.74 (−1.00, −0.48) | 2.63 E-06 | −0.80 (−1.16, −0.43) | 2.81 E-05 |
| 7-methylxanthine | HMDB0001991 | −0.52 (−0.81, −0.23) | 0.007 | −0.70 (−1.05, −0.34) | 1.47 E-04 |
| 1,7-dimethyluric acid | HMDB0011103 | −0.58 (−0.85, −0.31) | 0.002 | −0.72 (−1.10, −0.33) | 2.73 E-04 |
| 3-methylxanthine | HMDB0001886 | −0.55 (−0.84, −0.26) | 0.006 | −0.66 (−1.03, −0.30) | 4.00 E-04 |
| C52:3 TAG | HMDB0005384 | 0.43 (0.13, 0.73) | 0.042 | 0.50 (0.17, 0.82) | 0.003 |
| Linoleate | HMDB0000673 | 0.61 (0.30, 0.92) | 0.005 | 0.48 (0.11, 0.84) | 0.011 |
| C18:3 CE | HMDB0010370 | −0.56 (−0.84, −0.28) | 0.005 | −0.38 (−0.72, −0.03) | 0.032 |
| Glycine | HMDB0000123 | −0.42 (−0.70, −0.15) | 0.032 | −0.34 (−0.68, 0.01) | 0.055 |
| Isoleucine | HMDB0000172 | 0.38 (0.12, 0.65) | 0.042 | 0.23 (−0.11, 0.58) | 0.190 |
| Uracil | HMDB0000300 | −0.41 (−0.70, −0.13) | 0.042 | −0.31 (−0.61, 0.02) | 0.067 |
| C18:3 LPC | HMDB0010387 | −0.50 (−0.80, −0.20) | 0.016 | −0.26 (−0.59, 0.08) | 0.131 |
| C24:0 LPC | HMDB0008038 | −0.40 (−0.68, −0.13) | 0.042 | −0.19 (−0.51, 0.14) | 0.261 |
| Sebacate | HMDB0000792 | −0.50 (−0.81, −0.18) | 0.027 | 0.17 (−0.17, 0.52) | 0.328 |
| C34:0 PS | HMDB0012356 | −0.39 (−0.67, −0.12) | 0.045 | −0.16 (−0.53, 0.20) | 0.374 |
| Cortisol | HMDB0000063 | −0.55 (−0.84, −0.26) | 0.006 | −0.20 (−0.55, 0.15) | 0.265 |
| C12 carnitine | HMDB0002250 | 0.44 (0.15, 0.73) | 0.032 | 0.20 (−0.16, 0.57) | 0.277 |
| C12:1 carnitine | HMDB0013326 | 0.53 (0.24, 0.81) | 0.007 | 0.16 (−0.21, 0.52) | 0.402 |
| C14:1 carnitine | HMDB0002014 | 0.44 (0.15, 0.72) | 0.032 | 0.22 (−0.15, 0.58) | 0.245 |
| C14:2 carnitine | HMDB0013331 | 0.42 (0.14, 0.71) | 0.040 | 0.22 (−0.15, 0.58) | 0.238 |
| C56:5 TAG | HMDB0005406 | 0.45 (0.13, 0.77) | 0.048 | −0.06 (−0.40, 0.28) | 0.910 |
| C56:8 TAG | HMDB0005392 | 0.50 (0.21, 0.79) | 0.012 | −0.02 (−0.29, 0.26) | 0.721 |
HMDB, Human Metabolome Database
1
All values are beta estimates obtained from multivariable-adjusted linear regression models with 5-SD increments of the EDIP score as the main predictor of interest and metabolite as the main response variable of interest.
2
Metabolites in bold font are the 10 replicated metabolites
3
Models were adjusted for body mass index (continuous) age, physical activity, educational level, race/ethnicity, aspirin/NSAIDs use, smoking status, WHI Hormone Therapy trial arm, CHD case-control status.
4
Statistical significance was defined as false-discovery rate adjusted p<0.05.