Table 1.
Top associations between metabolites and NASH-fibrosis variants in the EPIC-Norfolk and Fenland cohorts
| Group | Metabolite | Beta (SE) | P | Q | n | Cohort | Method |
|---|---|---|---|---|---|---|---|
| rs72613567TA>T in HSD17B13 | |||||||
| Amino acid | 3-methylglutarylcarnitine | .05 (.02) | 5.3E-04 | 0.024 | 9756 | EPIC | Untargeted |
| Phosphatidylcholines | LysoPC (C14:0) | −.02 (.01) | 1.3E-04 | 0.006 | 9317 | Fenland | Targeted |
| Phosphatidylcholines | LysoPC (C20:3) | −.02 (.01) | 2.9E-04 | 0.012 | 9317 | Fenland | Targeted |
| Phosphatidylcholines | DiacylPC (C40:6) | .05 (.02) | 6.3E-04 | 0.028 | 9902 | EPIC | Untargeted |
| rs641738C>T near MBOAT7 | |||||||
| Fatty acid | Fatty acid (C20:3n6) | .04 (.01) | 2.5E-04 | 0.010 | 4279 | Fenland | Targeted |
| Lysolipid | LysoPI (C20:4) | −.18 (.01) | 9.3E-38 | 3.0E-34 | 9902 | EPIC | Untargeted |
| Lysolipid | LysoPI (C18:2) | .17 (.01) | 2.1E-34 | 5.2E-31 | 9902 | EPIC | Untargeted |
| Phosphatidylcholines | DiacylPC (C26:0) | −.02 (.01) | 0.001 | 0.037 | 9317 | Fenland | Targeted |
| Phosphatidylinositol | PI (C38:4) | −.24 (.01) | 1.8E-62 | 1.7E-58 | 9902 | EPIC | Untargeted |
| Phosphatidylinositol | PI (C36:2) | .21 (.01) | 1.1E-50 | 5.4E-47 | 9902 | EPIC | Untargeted |
| rs2642438A>G in MTARC1 | |||||||
| Lysolipid | LysoPC (C22:5) | .06 (.02) | 6.5E-05 | 0.005 | 9858 | EPIC | Untargeted |
| Lysolipid | LysoPC (C15:0) | .05 (.02) | 6.1E-04 | 0.028 | 9901 | EPIC | Untargeted |
| Lysolipid | LysoPC (C14:0) | .05 (.02) | 0.001 | 0.039 | 9901 | EPIC | Untargeted |
| Phosphatidylcholines | DiacylPC (C40:5) | .07 (.02) | 7.5E-06 | 8.6E-04 | 9901 | EPIC | Untargeted |
| Phosphatidylcholines | Alkylacyl PC (C34:1) | .02 (.01) | 8.6E-04 | 0.026 | 9317 | Fenland | Targeted |
| Sphingomyelin | SM (C20:2) | .02 (.01) | 3.9E-04 | 0.015 | 9317 | Fenland | Targeted |
| Sphingomyelin | SMOH (C22:2) | .02 (.01) | 5.4E-04 | 0.019 | 9317 | Fenland | Targeted |
| Sphingomyelin | SM (C32:2) | .05 (.01) | 3.9E-04 | 0.019 | 9901 | EPIC | Untargeted |
| rs738409C>G in PNPLA3 | |||||||
| Amino acid | N-acetylmethionine | −.09 (.02) | 3.6E-07 | 5.8E-05 | 9893 | EPIC | Untargeted |
| Amino acid | Tyrosine | .02 (.01) | 1.3E-04 | 0.006 | 9317 | Fenland | Targeted |
| Amino acid | 3-methylglutarylcarnitine | .06 (.02) | 1.2E-04 | 0.008 | 9756 | EPIC | Untargeted |
| Fatty acid | Fatty acid (C20:4n6) | −.03 (.01) | 0.001 | 0.037 | 4279 | Fenland | Targeted |
| Triacylglyceride | TG (C56:6) | .07 (.02) | 7.3E-05 | 0.004 | 1356 | Fenland | Untargeted |
| Triacylglyceride | TG (C56:5) | .06 (.02) | 2.6E-04 | 0.011 | 1356 | Fenland | Untargeted |
| Triacylglyceride | TG (C59:7) | .06 (.02) | 5.6E-04 | 0.019 | 1356 | Fenland | Untargeted |
| rs58542926C>T in TM6SF2 | |||||||
| Fatty acid | Fatty acid (C20:4n6) | −.03 (.01) | 1.9E-05 | 0.001 | 4279 | Fenland | Targeted |
| Fatty acid | Fatty acid (C20:3n6) | −.09 (.03) | 3.7E-04 | 0.019 | 9891 | EPIC | Untargeted |
| Lysolipid | LysoPC (C14:0) | −.1 (.03) | 1.7E-04 | 0.010 | 9901 | EPIC | Untargeted |
| Phosphatidylcholines | DiacylPC (C34:4) | −.03 (.004) | 2.0E-10 | 7.8E-08 | 9317 | Fenland | Targeted |
| Phosphatidylcholines | DiacylPC (C34:4) | −.15 (.03) | 1.0E-08 | 2.5E-06 | 9901 | EPIC | Untargeted |
| Phosphatidylcholines | Alkylacyl PC (C40:5) | −.02 (.004) | 1.0E-07 | 2.3E-05 | 9317 | Fenland | Targeted |
| Phosphatidylcholines | DiacylPC (C34:4) | −.15 (.03) | 1.7E-07 | 3.0E-05 | 7991 | EPIC | Untargeted |
| Phosphatidylcholines | Alkylacyl PC (C38:0) | −.02 (.004) | 1.8E-07 | 3.2E-05 | 9317 | Fenland | Targeted |
| Sphingomyelin | SMOH (C22:1) | −.01 (.004) | 7.3E-04 | 0.023 | 9317 | Fenland | Targeted |
| Sphingomyelin | SMOH (C14:1) | −.01 (.004) | 0.001 | 0.038 | 9317 | Fenland | Targeted |
Beta represents the change in 1 normalized standard deviation of each metabolite per effect allele (Supplementary Material, Table S8 for a full list of significant associations, Q < 0.05). DG, diacylglycerol; GPC, glycerophosphatidylcholine; GPI, glycerophosphatidylinositol; PC, phosphatidylcholine; Q, Q-value (false discovery rate-corrected P-value); SM, sphingomyelin; SMOH, sphingomyelin hydroxide; TG, triacylglycerol.