Table 2. see also Figures S2 and S3 and Tables S2 and S3. Genome-wide significant loci associated with metabolites.
31 genetic loci with at least one genome-wide significant metabolite association are shown. Citations are provided for previously established associations between these loci and other traits.
| Locus | Trait | SNP | ch | Major/ minor Allele |
MAF | Beta | s.e. | P-value | Previous genome-wide associations |
|---|---|---|---|---|---|---|---|---|---|
| AGXT2 | β-aminoisobutyric acid | rs37370 | 5 | T/C | 0.10 | 1.02 | 0.05 | 5.8E-83 | β-aminoisobutyric acid (Suhre et al., 2011b) |
| FADS1-3 | PC 38:4 PC 36:4 LPC 20:4 CE 20:4 PC 38:5 LPC 20:5 CE 20:5 TAG 58:10 LPE 18:2 TAG 58:11 LPE 20:4 LPC 22:6 PC 34:2 PC 40:6 PC 36:2 PC 34:3 CE 16:0 LPC 20:3 CE 18:3 TAG 54:4 |
rs174545 rs102275 rs174550 rs174547 rs174535 rs174548 rs174548 rs174548 rs4246215 rs174556 rs174548 rs174550 rs174574 rs174535 rs174541 rs174576 rs174548 rs968567 rs174535 rs174550 |
11 | C/G T/C T/C T/C T/C C/G C/G C/G G/T C/T C/G T/C C/A T/C T/C C/A C/G C/T T/C T/C |
0.33 0.33 0.33 0.33 0.33 0.29 0.29 0.29 0.36 0.29 0.29 0.33 0.33 0.33 0.36 0.33 0.29 0.15 0.33 0.33 |
−0.54 −0.45 −0.45 −0.44 −0.41 −0.36 −0.34 −0.30 0.29 −0.30 −0.30 −0.26 0.26 −0.26 0.25 0.23 −0.23 0.31 −0.21 0.19 |
0.03 0.03 0.03 0.03 0.03 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.05 0.04 0.04 |
2.7E-61 1.9E-41 9.7E-41 4.7E-37 1.4E-32 1.6E-23 7.8E-21 8.1E-17 2.4E-16 2.5E-16 7.0E-16 1.3E-13 1.3E-13 3.5E-13 2.6E-12 1.7E-10 1.8E-10 4.4E-10 5.5E-09 4.8E-08 |
Phospholipids (Lemaitre et al., 2011) Total, HDL, and LDL cholesterol (Teslovich et al., 2010) Triglycerides (Teslovich et al., 2010) Lipid sub-species (Kettunen et al., 2012; Suhre et al., 2011a) Fasting glucose (Dupuis et al., 2010) Crohn's disease (Franke et al., 2010) Resting heart rate (Eijgelsheim et al., 2010) |
| CPS1 | Glycine Creatine |
rs7422339 rs7422339 |
2 | C/A C/A |
0.31 0.31 |
0.53 0.24 |
0.03 0.04 |
2.4E-58 2.5E-11 |
Creatinine production (Kottgen et al., 2010) Homocysteine (Lange et al., 2010) Fibrinogen (Danik et al., 2009) |
| HPS1 | Asymmetric dimethylarginine |
rs6584192 | 10 | T/G | 0.37 | −0.41 | 0.03 | 3.5E-33 | |
| DMGDH | Dimethlyglycine | rs248386 | 5 | C/A | 0.19 | 0.50 | 0.04 | 6.6E-33 | |
| SLC16A9 | Carnitine | rs1171617 | 10 | T/G | 0.23 | −0.42 | 0.04 | 5.9E-26 | Carnitine (Suhre et al., 2011a) Uric acid (Kolz et al., 2009) |
| SERPINA7 | Thyroxine | rs7883218 | X | A/G | 0.12 | −0.39 | 0.04 | 1.3E-20 | |
| PRODH | Proline | rs2078743 | 22 | G/A | 0.09 | 0.49 | 0.06 | 2.2E-14 | Proline (Kettunen et al., 2012) |
| GMPR | Xanthosine | rs9477074 | 6 | T/C | 0.37 | 0.25 | 0.03 | 3.0E-14 | LDL cholesterol (Waterworth et al., 2010) |
| SLC6A13 | β-aminoisobutyric acid | rs11613331 | 12 | A/G | 0.49 | −0.23 | 0.03 | 2.0E-12 | Creatinine production (Kottgen et al., 2010) |
| LIPC | LPE 16:0 | rs1532085 | 15 | G/A | 0.38 | 0.24 | 0.03 | 3.7E-12 | Total and HDL cholesterol (Teslovich et al., 2010) Triglycerides (Teslovich et al., 2010) Lipid sub-species (Demirkan et al., 2012; Gieger et al., 2008; Kettunen et al., 2012) Metabolic syndrome (Kristiansson et al., 2012) Macular degeneration (Neale et al., 2010) |
| GCKR | Alanine Lactate α-hydroxybutyrate TAG 50:4 TAG 48:2 TAG 50:3 PC 34:3 PC 32:2 TAG 48:3 |
rs1260326 rs1260326 rs1260326 rs1260326 rs1260326 rs1260326 rs1260326 rs1260326 rs1260326 |
2 | C/T C/T C/T C/T C/T C/T C/T C/T C/T |
0.45 0.45 0.45 0.45 0.45 0.45 0.45 0.45 0.45 |
0.23 0.24 0.22 0.20 0.19 0.19 0.18 0.19 0.18 |
0.03 0.04 0.04 0.03 0.03 0.03 0.03 0.03 0.03 |
7.6E-12 3.3E-11 1.3E-09 3.4E-09 2.5E-08 2.6E-08 2.9E-08 3.9E-08 4.9E-08 |
Triglycerides (Teslovich et al., 2010) Total cholesterol (Teslovich et al., 2010) Phospholipids (Demirkan et al., 2012; Lemaitre et al., 2011) CRP (Dehghan et al., 2011; Ridker et al., 2008) Chronic kidney disease (Kottgen et al., 2010) Glycemic traits (Dupuis et al., 2010; Saxena et al., 2010) Uric acid (Kolz et al., 2009; Yang et al., 2010) Alanine/glycine (Kettunen et al., 2012) Platelet count (Gieger et al., 2011) Albumin (Kamatani et al., 2010; Kim et al., 2011) Glucose/mannose (Suhre et al., 2011a) Crohn's disease (Franke et al., 2010) |
| APOA1/C3/A4/A5 | DAG 36:2 TAG 56:3 TAG 56:10 TAG 54:2 TAG 52:4 TAG 54:3 DAG 34:2 TAG 52:5 DAG 36:1 TAG 52:3 TAG 54:5 |
rs964184 rs964184 rs964184 rs964184 rs964184 rs964184 rs964184 rs964184 rs964184 rs12294259 rs964184 |
11 | C/G C/G C/G C/G C/G C/G C/G C/G C/G C/T C/G |
0.14 0.14 0.14 0.14 0.14 0.14 0.14 0.14 0.14 0.06 0.14 |
0.33 0.32 0.31 0.31 0.30 0.29 0.28 0.28 0.28 0.39 0.26 |
0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.07 0.05 |
1.3E-11 2.8E-11 1.5E-10 1.9E-10 2.4E-10 3.2E-09 6.0E-09 7.4E-09 8.2E-09 1.7E-08 4.8E-08 |
Triglycerides (Teslovich et al., 2010) HDL cholesterol (Teslovich et al., 2010) Coronary artery disease (Schunkert et al., 2011) |
| DDAH1 | NG-monomethyl-arginine | rs18582 | 1 | A/G | 0.35 | 0.24 | 0.04 | 2.2E-11 | |
| SLCO1B1 | LPE 20:4 | rs4149056 | 12 | T/C | 0.15 | 0.30 | 0.05 | 1.1E-10 | Bilirubin (Johnson et al., 2009) Statin-induced myopathy (Link et al., 2008) Lipid sub-species (Suhre et al., 2011a) |
| AGA | Asparagine | rs4690522 | 4 | C/A | 0.32 | 0.25 | 0.04 | 1.4E-10 | |
| SYNE2 | SM 14:0 | rs11158519 | 14 | G/A | 0.14 | 0.31 | 0.05 | 3.2E-10 | Lipid sub-species (Illig et al., 2010) Atrial fibrillation (Ellinor et al., 2012) Pulmonary function decline (Imboden et al., 2012) |
| UMPS | Orotic acid | rs9844948 | 3 | C/A | 0.16 | −0.32 | 0.05 | 7.6E-10 | |
| PDE4D | SM 24:1 | rs4700347 | 5 | A/G | 0.16 | 0.28 | 0.05 | 3.4E-09 | Stroke (Song et al., 2006) Esophageal cancer (Wu et al., 2011) Asthma (Himes et al., 2009) Sleepiness (Gottlieb et al., 2007) |
| SEC61G | CE 20:4 | rs11981543 | 7 | C/A | 0.11 | 0.32 | 0.05 | 4.2E-09 | |
| rs6593086 | TAG 58:9 TAG 56:7 TAG 58:8 |
rs6593086 rs6593086 rs6593086 |
7 | C/G C/G C/G |
0.34 0.34 0.34 |
−0.20 −0.20 −0.20 |
0.03 0.03 0.03 |
4.4E-09 6.1E-09 2.0E-08 |
|
| UGT1A5 | Xanthurenate | rs4148325 | 2 | C/T | 0.31 | 0.23 | 0.04 | 4.9E-09 | Bilirubin (Johnson et al., 2009; Sanna et al., 2009) |
| SLC7A9 | NG-monomethyl-arginine | rs8101881 | 19 | T/C | 0.44 | −0.20 | 0.03 | 5.0E-09 | Chronic kidney disease (Kottgen et al., 2010) Creatinine level (Chambers et al., 2010) Urine lysine/valine (Suhre et al., 2011b) |
| ABP1 | γ-aminoisobutyric acid | rs6977081 | 7 | G/T | 0.34 | 0.23 | 0.04 | 5.4E-09 | |
| PHGDH | Serine | rs477992 | 1 | G/A | 0.32 | −0.21 | 0.04 | 6.5E-09 | Serine (Suhre et al., 2011a) |
| SLC16A10 | Tyrosine | rs411604 | 6 | G/A | 0.36 | 0.20 | 0.04 | 1.0E-08 | Isoleucine/Tyrosine (Suhre et al., 2011a) Alanine/Tyrosine (Kettunen et al., 2012) |
| CSNK1G3 | Indoxylsulfate | rs875480 | 5 | A/G | 0.24 | 0.25 | 0.04 | 1.4E-08 | |
| GNAL | CE16:0 | rs1786573 | 18 | T/C | 0.27 | 0.21 | 0.04 | 2.8E-08 | |
| DGKB | Indole propionate | rs12699655 | 7 | T/G | 0.45 | −0.21 | 0.04 | 3.1E-08 | Glycemic traits (Dupuis et al., 2010) |
| TBX18 | DAG 36:1 | rs4510639 | 6 | C/T | 0.25 | 0.21 | 0.04 | 3.5E-08 | |
| NTAN1 | CE 20:3 | rs3803573 | 16 | C/T | 0.28 | −0.21 | 0.04 | 4.7E-08 | Bone mineral density (Estrada et al., 2012) |
SNP, single nucleotide polymorphism; MAF, minor allele frequency; ch, chromosome; s.e., standard error; PC, phosphatidylcholine; LPC, lysophosphatidylcholine; CE, cholesterol ester; TAG, triacylglycerol; LPE, lysophosphatidylethanolamine; DAG, diacylglycerol; SM, sphingomyelin.