Table 5.
Summary of hierarchical modelling fits for selected genetic effects (βG), prior covariates (Z'π) and prior standard deviations (σβ and σπ) for simulation with different intermediates as the causal variable, using the Z matrix derived from independent data from the same simulation model (see text).
| Simulated causal variable | ||||
|---|---|---|---|---|
| Homocysteine concentration | Pyrimidine synthesis (TS) | Purine synthesis (AICART) | DNA methylation (DNMT) | |
| Genetic main effects | ||||
| G2: TS | 0.06 (0.10) | -0.97 (0.11) | 0.15 (0.11) | 0.12 (0.10) |
| G3: MTD | -0.35 (0.11) | 1.09 (0.12) | -0.81 (0.12) | 0.59 (0.11) |
| G4: MTCH | -0.26 (0.14) | 0.60 (0.13) | -0.68 (0.14) | 0.35 (0.12) |
| G5: PGT | 0.01 (0.05) | 0.05 (0.18) | -1.90 (0.19) | -0.04 (0.16) |
| G7: FTS | 0.13 (0.12) | 0.06 (0.14) | -0.62 (0.13) | 0.11 (0.12) |
| G8: FTD | -0.12 (0.13) | -0.34 (0.14) | 0.59 (0.13) | -0.26 (0.12) |
| G9: SHMT | 0.29 (0.12) | -0.72 (0.10) | -0.53 (0.12) | -0.43 (0.10) |
| G10: MTHFR | 0.34 (0.10) | -0.04 (0.10) | 0.13 (0.11) | -0.70 (0.11) |
| G11: MS | 0.23 (0.10) | -0.18 (0.10) | -0.47 (0.11) | -0.13 (0.10) |
| G12: SAHH | -0.78 (0.13) | 0.22 (0.13) | 0.34 (0.14) | -0.54 (0.12) |
| G13: CBS | 1.43 (0.13) | 0.07 (0.12) | 0.06 (0.12) | 0.01 (0.11) |
| Prior covariates | ||||
| π1: homocysteine | 1.65 (0.81) | -0.16 (0.63) | -0.02 (0.70) | 0.00 (0.57) |
| π2: vTS | -0.18 (0.57) | 1.45 (0.61) | 0.08 (0.62) | 0.17 (0.54) |
| π3: vAICART | 0.11 (0.59) | 20.35 (0.61) | 2.19 (0.81) | -0.28 (0.55) |
| π4: vDNMT | -0.01 (0.69) | 0.27 (0.69) | -0.01 (0.70) | 1.01 (0.73) |
| Posterior standard deviations (SDs) | ||||
| σβ = SD(β|Z) | 0.49 (0.12) | 0.48 (0.11) | 0.52 (0.11) | 0.47 (0.11) |
| σπ = SD(π) | 1.14 (0.48) | 1.14 (0.47) | 1.33 (0.58) | 0.99 (0.40) |
Bolded entries have posterior credibility intervals that exclude zero
AICART, aminoimidazolecarboxamide ribonucleotide transferase; CBS, cystathionine b-reductase; DNMT, DNA methyltransferase; FTD, 10-formyltetrahydrofolate dehydrogenase; FTS, 10-formyltetrahydrofolate synthase; MS, methionine synthase; MTCH, 5,10-methylenetetrahydrofolate cyclohydrolase; MTD, 5,10-methylenetetrahydrofolate dehydrogenase; MTHFR, 5,10-methylenetetrahydrofolate reductase; PGT, phosphoribosyl glycinamide transferase; SAHH, S-adenosylhomocysteine; SHMT, serine hydroxymethyltransferase; TS, thymidylate synthase.