Table 2. BCAA pathway associations.
| Position in the BCAA Pathway | Category | Metabolite | Beta (SE) for Metabolite per rs1440581-C Allele | p-Value | RR (95% CI) of Type 2 Diabetes per 1-SD Increase in Metabolite Level | p-Value |
|---|---|---|---|---|---|---|
| Upstream of BCKD | BCAA | Isoleucine | 0.09 (0.02) | 6.0 × 10−8 | 1.31 (1.11–1.54) | 0.0012 |
| Leucine | 0.11 (0.01) | 8.2 × 10−19 | 1.22 (1.03–1.43) | 0.018 | ||
| Valine | 0.12 (0.02) | 4.6 × 10−12 | 1.34 (1.12–1.61) | 0.0013 | ||
| BCKA | 3-methyl-2-oxovalerate | 0.13 (0.01) | 1.5 × 10−19 | 1.62 (1.35–1.95) | 3.1 × 10−7 | |
| 3-methyl-2-oxobutyrate | 0.13 (0.02) | 3.3 × 10−14 | 1.60 (1.33–1.92) | 5.8 × 10−7 | ||
| 3-hydroxy-2-ethylpropionate | 0.12 (0.02) | 2.4 × 10−13 | 1.40 (1.21–1.63) | 1.2 × 10−5 | ||
| BCKA-derived | 2-hydroxy-3-methylvalerate | 0.11 (0.04) | 0.0042 | 1.36 (1.18–1.58) | 3.4 × 10−5 | |
| Alpha-hydroxyisovalerate | 0.09 (0.02) | 8.8 × 10−9 | 1.22 (1.05–1.41) | 0.0098 | ||
| Alpha-hydroxyisocaproate | 0.12 (0.04) | 0.00066 | 1.22 (1.03–1.45) | 0.025 | ||
| Downstream of BCKD | Other | 3-hydroxyisobutyrate | 0.01 (0.04) | 0.71 | 1.32 (1.13–1.54) | 0.00047 |
| Acylcarnitine | Propionylcarnitine | −0.04 (0.02) | 0.010 | 1.15 (0.98–1.34) | 0.078 | |
| Isovalerylcarnitine | −0.01 (0.02) | 0.42 | 1.13 (0.97–1.32) | 0.11 | ||
| Isobutyrylcarnitine | 0.02 (0.02) | 0.13 | 0.82 (0.70–0.96) | 0.014 |
The table reports the association of a genetic predisposition to higher BCAA levels with the levels of other metabolites in the BCAA pathway. The table also reports the association of higher levels of metabolites in the BCAA pathway with the risk of incident type 2 diabetes. Beta coefficients are in standardised units.
BCAA, branched-chain amino acid; BCKA, branched-chain alpha-ketoacid; BCKD, branched-chain alpha-ketoacid dehydrogenase; RR, relative risk; SE, standard error; SD, standard deviation.