Table 1.
Summary results from Mendelian randomization, meta-analysis, and colocalization for metabolome-wide Mendelian randomization identified metabolites
| Mendelian randomization discovery |
Mendelian randomization replication |
Meta-analysis |
Colocalization |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Tissue | Metabolite | Odds ratio | P | Odds ratio | P | Odds ratio (95% confidence interval) | P | PP4 > 80%a | Subpathway | Category |
| Plasma | 1-Stearoyl-2-arachidonoyl-GPC (18:0/20:4) | 1.10 | 4.09E-22 | 1.10 | 1.05E-03 | 1.10 (1.08 to 1.12) | 1.81E-24 | Yes | Phosphatidylcholine | Tier1 |
| Plasma | 1-Palmitoyl-2-arachidonoyl-GPC (16:0/20:4n6) | 1.11 | 4.64E-22 | 1.11 | 1.74E-03 | 1.11 (1.09 to 1.13) | 3.31E-24 | Yes | Phosphatidylcholine | Tier1 |
| Plasma | 1,2-Dilinoleoyl-GPC (18:2/18:2) | 0.80 | 1.86E-21 | 0.81 | 1.62E-03 | 0.80 (0.77 to 0.84) | 1.23E-23 | Yes | Phosphatidylcholine | Tier1 |
| Plasma | 1-Linoleoyl-2-linolenoyl-GPC (18:2/18:3)* | 0.76 | 1.86E-21 | 0.77 | 1.62E-03 | 0.76 (0.72 to 0.80) | 1.23E-23 | Yes | Phosphatidylcholine | Tier1 |
| Plasma | 1-Palmitoyl-2-docosahexaenoyl-GPC (16:0/22:6) | 1.47 | 1.86E-21 | 1.46 | 1.62E-03 | 1.47 (1.37 to 1.59) | 1.23E-23 | Yes | Phosphatidylcholine | Tier1 |
| Plasma | Adrenate (22:4n6) | 1.42 | 1.86E-21 | 1.41 | 1.62E-03 | 1.42 (1.33 to 1.52) | 1.23E-23 | Yes | Long chain polyunsaturated fatty acid | Tier1 |
| Plasma | EPA (20:5n3) | 1.37 | 1.86E-21 | 1.36 | 1.62E-03 | 1.37 (1.29 to 1.45) | 1.23E-23 | Yes | Long chain polyunsaturated fatty acid | Tier1 |
| Plasma | 1-Arachidonylglycerol (20:4) | 1.27 | 2.16E-21 | 1.27 | 1.09E-03 | 1.27 (1.21 to 1.33) | 9.87E-24 | Yes | Monoacylglycerol | Tier1 |
| Plasma | Docosatrienoate (22:3n6)* | 1.39 | 2.58E-21 | 1.36 | 2.71E-03 | 1.39 (1.30 to 1.48) | 2.81E-23 | Yes | Long chain polyunsaturated fatty acid | Tier1 |
| Plasma | 1-(1-Enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4)* | 1.25 | 2.59E-21 | 1.24 | 1.79E-03 | 1.25 (1.19 to 1.30) | 1.88E-23 | Yes | Plasmalogen | Tier1 |
| Plasma | 1-Arachidonoyl-GPC (20:4n6)* | 1.12 | 2.59E-21 | 1.12 | 1.79E-03 | 1.12 (1.10 to 1.15) | 1.87E-23 | Yes | Lysophospholipid | Tier1 |
| Plasma | Arachidonate (20:4n6) | 1.23 | 2.59E-21 | 1.22 | 1.79E-03 | 1.23 (1.18 to 1.27) | 1.88E-23 | Yes | Long chain polyunsaturated fatty acid | Tier1 |
| Plasma | Nisinate (24:6n3) | 1.50 | 4.48E-21 | 1.47 | 2.60E-03 | 1.50 (1.38 to 1.63) | 4.65E-23 | Yes | Long chain polyunsaturated fatty acid | Tier1 |
| Plasma | Stearidonate (18:4n3) | 1.69 | 4.48E-21 | 1.64 | 2.60E-03 | 1.69 (1.52 to 1.87) | 4.65E-23 | Yes | Long chain polyunsaturated fatty acid | Tier1 |
| Plasma | Arachidonoylcholine | 1.39 | 6.23E-21 | 1.39 | 1.63E-03 | 1.39 (1.30 to 1.48) | 4.14E-23 | Yes | Fatty acid metabolism (acyl choline) | Tier1 |
| Plasma | Hydroxypalmitoyl sphingomyelin (d18:1/16:0(OH))** | 0.80 | 8.23E-21 | 0.80 | 1.87E-03 | 0.80 (0.76 to 0.84) | 6.20E-23 | Yes | Sphingomyelins | Tier1 |
| Plasma | Docosapentaenoate (n3 DPA; 22:5n3) | 1.54 | 5.14E-20 | 1.39 | 1.87E-02 | 1.52 (1.40 to 1.66) | 4.08E-21 | Yes | Long chain polyunsaturated fatty acid | Tier1 |
| Plasma | 1-Lignoceroyl-GPC (24:0) | 1.56 | 3.25E-18 | 1.65 | 7.58E-04 | 1.57 (1.43 to 1.72) | 1.12E-20 | Yes | Lysophospholipid | Tier1 |
| Plasma | γ-Glutamylthreonine | 1.38 | 1.66E-07 | 1.74 | 4.57E-03 | 1.44 (1.20 to 1.72) | 6.18E-05 | Yes | γ-Glutamyl amino acid | Tier1 |
| Plasma | Mannonate* | 1.18 | 1.66E-07 | 1.32 | 4.57E-03 | 1.20 (1.10 to 1.31) | 6.18E-05 | Yes | Food component/plant | Tier1 |
| Plasma | Mannose | 1.14 | 1.66E-07 | 1.25 | 4.57E-03 | 1.16 (1.08 to 1.25) | 6.17E-05 | Yes | Fructose, mannose, and galactose metabolism | Tier1 |
| Plasma | Docosapentaenoate (n6 DPA; 22:5n6) | 1.65 | 1.13E-21 | 1.28 | 8.37E-02 | 1.51 (1.19 to 1.91) | 6.83E-04 | Yes | Long chain polyunsaturated fatty acid | Tier2 |
| Plasma | Sphingomyelin (d18:2/14:0, d18:1/14:1)* | 1.85 | 3.34E-18 | 1.97 | 1.01E-03 | 1.86 (1.63 to 2.13) | 1.47E-20 | No | Sphingomyelins | Tier2 |
| Plasma | 1-(1-Enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4)* | 1.13 | 5.96E-07 | 1.09 | 3.14E-01 | 1.13 (1.08 to 1.18) | 3.77E-07 | Yes | Plasmalogen | Tier2 |
| Plasma | Galactonate | 0.73 | 4.71E-06 | 0.62 | 5.44E-03 | 0.71 (0.62 to 0.81) | 1.22E-07 | No | Fructose, mannose, and galactose metabolism | Tier2 |
| Plasma | Deoxycholic acid glucuronide | 0.96 | 7.14E-06 | 0.95 | 1.59E-02 | 0.96 (0.94 to 0.97) | 4.17E-07 | No | Secondary bile acid metabolism | Tier2 |
| Plasma | Cholic acid glucuronide | 0.90 | 1.06E-05 | 0.87 | 1.96E-02 | 0.89 (0.86 to 0.94) | 7.15E-07 | No | Primary bile acid metabolism | Tier2 |
| Plasma | X-19141 | 0.95 | 1.06E-05 | 0.94 | 1.95E-02 | 0.95 (0.93 to 0.97) | 7.08E-07 | No | Unknown | Tier2 |
| Plasma | X-25790 | 1.32 | 1.22E-07 | 1.17 | 3.54E-01 | 1.30 (1.18 to 1.44) | 9.81E-08 | No | Unknown | Tier3 |
| Plasma | X-17357 | 0.91 | 5.77E-05 | 1.02 | 7.66E-01 | 0.95 (0.85 to 1.05) | 3.25E-01 | No | Unknown | Tier3 |
| Urine | Lactose | 1.14 | 4.40E-05 | 1.27 | 1.31E-03 | 1.18 (1.06 to 1.30) | 1.50E-03 | Yes | Disaccharides and oligosaccharides | Tier1 |
| Urine | X-19141 | 0.94 | 9.97E-06 | 0.92 | 1.90E-02 | 0.94 (0.91 to 0.96) | 6.56E-07 | No | Unknown | Tier2 |
| Urine | X-19434 retired for cholic acid glucuronide | 0.96 | 1.12E-05 | 0.95 | 3.20E-02 | 0.95 (0.94 to 0.97) | 1.09E-06 | No | Unknown | Tier2 |
| Urine | 11-Ketoetiocholanolone sulfate | 1.06 | 1.16E-05 | 1.08 | 1.94E-02 | 1.06 (1.04 to 1.09) | 7.77E-07 | No | Androgenic steroids | Tier2 |
a
PP4 values were all higher than 80% under different windows (±250 kilobase, kb or ±500 kb). PP4 = posterior probability for H4; E = exponent.