Table 3.
Estimates of the effect of genetically instrumented liver enzymes (ALT, ALP, and GGT) (per 100% change in concentration) on BMI (standard deviation) using Mendelian randomization with different methodological approaches with and without potentially pleiotropic SNPs.
| Liver enzyme | Method | SNP | Men and women together using All-GIANTUKB | Men using GWAS Anthropometric 2015 BMI | Women using GWAS Anthropometric 2015 BMI | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Beta | 95% CI | MR-Egger | I2 | Beta | 95% CI | MR-Egger | I2 | Beta | 95% CI | MR-Egger | I2 | |||
| Intercept p-value | (p-value) | Intercept p-value | (p-value) | Intercept p-value | (p-value) | |||||||||
| ALT | IVW | 4 | −0.17 | −0.33 to −0.01 | — | 84.6% (<0.001) | −0.13 | −0.39 to 0.13 | — | 60.6% (0.05) | −0.19 | −0.34 to −0.04 | — | 0.0% (0.76) |
| 3 | −0.14 | −0.20 to −0.07 | — | 0.0% (<0.64) | −0.08 | −0.24 to 0.09 | — | 0.0% (0.39) | −0.18 | −0.34 to −0.03 | — | 0.0% (0.59) | ||
| 2 | −0.17 | −0.29 to −0.05 | — | — | −0.24 | −0.56 to 0.07 | — | — | −0.19 | −0.48 to 0.10 | — | — | ||
| WM | 4 | −0.13 | −0.20 to −0.05 | — | — | −0.06 | −0.25 to 0.12 | — | — | −0.19 | −0.36 to −0.02 | — | — | |
| 3 | −0.12 | −0.20 to −0.05 | — | — | −0.05 | −0.23 to 0.13 | — | — | −0.18 | −0.36 to −0.01 | — | — | ||
| MR-Egger | 4 | 0.02 | −0.25 to 0.30 | 0.11 | — | 0.24 | −0.09 to 0.58 | 0.01 | — | −0.16 | −0.48 to 0.15 | 0.85 | — | |
| 3 | −0.09 | −0.25 to 0.06 | 0.54 | — | 0.14 | −0.26 to 0.53 | 0.25 | — | −0.19 | −0.57 to 0.19 | 0.96 | — | ||
| ALP | IVW | 14 | −0.07 | −0.18 to 0.04 | — | 88.5% (<0.001) | 0.03 | −0.10 to 0.17 | — | 60.4% (0.002) | −0.08 | −0.21 to 0.04 | — | 58.7% (0.003) |
| 13 | −0.06 | −0.16 to 0.05 | — | 86.2% (<0.001) | 0.05 | −0.07 to 0.17 | — | 51.6% (0.02) | −0.08 | −0.21 to 0.05 | — | 61.3% (0.002) | ||
| 11 | −0.07 | −0.23 to 0.09 | — | 88.3% (<0.001) | −0.02 | −0.22 to 0.18 | — | 55.7% (0.01) | −0.17 | −0.33 to −0.01 | — | 34.6% (0.12) | ||
| WM | 14 | −0.05 | −0.11 to −0.001 | — | — | 0.07 | −0.03 to 0.18 | — | — | −0.06 | −0.16 to 0.04 | — | — | |
| 13 | −0.05 | −0.10 to −0.001 | — | — | 0.07 | −0.03 to 0.18 | — | — | −0.06 | −0.16 to 0.04 | — | — | ||
| 11 | −0.07 | −0.18 to 0.04 | — | — | −0.12 | −0.33 to 0.09 | — | — | −0.11 | −0.29 to 0.07 | — | — | ||
| MR-Egger | 14 | 0.03 | −0.17 to 0.22 | 0.23 | — | 0.15 | −0.06 to 0.37 | 0.18 | — | −0.04 | −0.26 to 0.18 | 0.63 | — | |
| 13 | −0.001 | −0.19 to 0.19 | 0.50 | — | 0.12 | −0.09 to 0.33 | 0.39 | — | −0.05 | −0.28 to 0.19 | 0.74 | — | ||
| 11 | 0.28 | −0.24 to 0.79 | 0.17 | — | 0.21 | −0.49 to 0.92 | 0.50 | — | 0.01 | −0.54 to 0.56 | 0.51 | — | ||
| GGT* | IVW | 26/25 | 0.04 | −0.01 to 0.08 | — | 85.6% (<0.001) | 0.01 | −0.05 to 0.07 | — | 40.7% (0.02) | 0.001 | −0.06 to 0.07 | — | 56.0% (<0.001) |
| 23/24 | 0.04 | −0.003 to 0.09 | — | 83.2% (<0.001) | 0.02 | −0.03 to 0.07 | — | 12.2% (0.29) | 0.02 | −0.05 to 0.08 | — | 50.4% (0.003) | ||
| WM | 26/25 | 0.03 | 0.01 to 0.06 | — | — | 0.02 | −0.05 to 0.09 | — | — | −0.01 | −0.07 to 0.06 | — | — | |
| 23/24 | 0.03 | 0.01 to 0.06 | — | — | 0.02 | −0.05 to 0.09 | — | — | −0.01 | −0.07 to 0.06 | — | — | ||
| MR-Egger | 26/25 | 0.06 | −0.05 to 0.17 | 0.65 | — | 0.05 | −0.09 to 0.19 | 0.47 | — | 0.04 | −0.11 to 0.19 | 0.56 | — | |
| 23/24 | 0.05 | −0.06 to 0.15 | 0.97 | — | 0.03 | −0.10 to 0.15 | 0.96 | — | −0.01 | −0.16 to 0.14 | 0.67 | — | ||
*Rs516246 (FUT2) predicting GGT is not available in GIANTUKB, 25 SNPs remained.
Excluded SNPs predicting ALT: rs2954021 (TRIB1) when SNP = 3, excluded rs738409 (PNPLA3) in addition when SNP = 2; excluded SNPs predicting ALP: rs2954021 (TRIB1), when SNP = 13; excluded rs281377 (FUT2) and rs579459 (ABO) in addition when SNP = 11; excluded SNPs predicting GGT: rs516246 (FUT2), rs1260326 (C2orf16, GCKR), and rs8038465 (CD276) when SNP = 23 from GWAS Anthropometric 2015 BMI projects, excluding SNPs: rs516246 (FUT2) and rs1260326 (C2orf16, GCKR) when SNP = 24 from GIANTUKB.
SNP: single nucleotide polymorphism; ALT: alanine aminotransferase; ALP: alkaline phosphatase; GGT: gamma glutamyltransferase; BMI: body mass index; IVW: inverse variance weighted; WM: weighted median.