Table 1.
Result of the GWAS
| Putative causal gene | Metabolite | Lead SNP information |
Previous reportsd | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| CHR | Position | Reference | ALT | ID | Freq. | Effect | SE | p -value | |||
| NBPF3 | O-Phosphoethanolamine | 1 | 21817126 | G | GGT | rs80212518 | 0.46 | 0.20 | 0.02 | 4.7E-22 | 1 |
| Phosphoric acid | 1 | 21820042 | A | G | rs12132412 | 0.23 | 0.20 | 0.03 | 8.5E-15 | 2 | |
| THEM4 | 3-Hydroxyisovaleric acid | 1 | 151890958 | A | C | rs61817697 | 0.30 | −0.16 | 0.02 | 3.1E-13 | 3 |
| ACP1 | Ribulose | 2 | 217,560 | AG | A | rs56350804 | 0.23 | −0.20 | 0.03 | 2.3E-14 | a |
| Arabinose | 2 | 268191 | G | T | rs56321614 | 0.22 | −0.24 | 0.02 | 2.6E-21 | b | |
| GCKR | Mannose | 2 | 27730940 | T | C | rs1260326 | 0.42 | 0.54 | 0.02 | 8.3E-181 | 3,4,5,6,7,8,9 |
| Threonine | 2 | 27744364 | ATT | A | rs373060500 | 0.43 | 0.13 | 0.02 | 2.8E-11 | 3,4,6,10,11,12 | |
| SLC1A4 | 2-Aminobutyric acid | 2 | 65225088 | G | GC | rs72538440 | 0.73 | 0.24 | 0.03 | 1.1E-20 | 3,4,5,6 |
| CPS1 | Acetylglycine | 2 | 211540507 | C | A | rs1047891 | 0.15 | 0.42 | 0.03 | 1.9E-45 | 3,4,5,6,13 |
| Glycine | 2 | 211540507 | C | A | rs1047891 | 0.15 | 1.08 | 0.02 | 1.2E-410 | 3,4,5,6,8,9,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30 | |
| Serine | 2 | 211540507 | C | A | rs1047891 | 0.15 | 0.37 | 0.03 | 1.5E-38 | 3,4,5,6,11,12,21,23,24 | |
| Creatinine | 2 | 211595900 | C | T | rs72933889 | 0.16 | 0.27 | 0.03 | 1.7E-22 | 2,12,31,32,33,34 | |
| GADL1 | beta-Alanine | 3 | 30768667 | T | TTTCCCA AATTTG |
rs147693330 | 0.52 | −0.45 | 0.02 | 7.0E-120 | 3,6 |
| SLC2A9 | Uric acid | 4 | 9984541 | G | T | rs9994216 | 0.58 | 0.17 | 0.02 | 5.1E-17 | 3,5,6,8,9,29,31,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53 |
| SOD3c | Threonic acid | 4 | 24801834 | C | G | rs1799895 | 0.04 | −0.87 | 0.06 | 1.4E-45 | b |
| ABCG2 | Uric acid | 4 | 89045331 | A | G | rs75544042 | 0.71 | −0.16 | 0.02 | 2.5E-13 | 3,31,35,36,37,39,40,41,42,43,44,46,49,50,54 |
| PPM1K | Valine | 4 | 89226422 | T | C | rs1440581 | 0.47 | 0.13 | 0.02 | 1.2E-10 | 3,5,11,12,16,26,55,56 |
| 2-Oxoisocaproic acid | 4 | 89228383 | T | C | rs7660693 | 0.46 | 0.13 | 0.02 | 3.6E-10 | 3,5,11 | |
| 3-Methyl-2-oxobutyric acid | 4 | 89228383 | T | C | rs7660693 | 0.46 | 0.15 | 0.02 | 1.1E-13 | 3,5,11 | |
| AGA | Aspartic acid | 4 | 178413876 | T | A | rs12642803 | 0.45 | −0.16 | 0.02 | 2.3E-13 | 3,12 |
| SDHA | Succinic acid | 5 | 195139 | C | T | rs118046653 | 0.02 | 0.68 | 0.07 | 1.9E-20 | 3 |
| AGXT2 | 3-Aminoisobutyric acid | 5 | 35030922 | G | A | rs6882350 | 0.80 | 1.13 | 0.02 | 3.9E-677 | 1,3,4,6,15,22,57,58,59,60,61,62 |
| NADK2 | Lysine | 5 | 36266859 | CTT | C | rs10556207 | 0.63 | 0.13 | 0.02 | 3.5E-10 | 3,11,12 |
| REV3L | Tyrosine | 6 | 111545540 | T | C | rs354551 | 0.69 | −0.17 | 0.02 | 5.6E-15 | 3,4,5,11,12,16,22,24,26,63,64 |
| PSPH | Serine | 7 | 56080426 | C | G | rs62457261 | 0.67 | 0.32 | 0.02 | 1.9E-51 | 3,4,5,6,11,12,13,17,21,23,24 |
| Glycine | 7 | 56081213 | A | AAAAT | rs36126335 | 0.67 | 0.14 | 0.02 | 6.7E-11 | 3,11,12,25,28 | |
| ADHFE1 | 2-Deoxytetronic acid | 8 | 67378275 | GT | G | rs35896820 | 0.41 | −0.17 | 0.02 | 1.9E-15 | 5 |
| PYCRL | Pipecolinic acid | 8 | 144687092 | T | C | rs896962 | 0.35 | −0.23 | 0.02 | 6.7E-26 | b |
| CCBL1 | Indolelactic acid | 9 | 131567995 | G | A | rs7854319 | 0.32 | −0.15 | 0.02 | 2.6E-12 | 3,4,5,6,24 |
| DHTKD1 | 2-Aminoadipic acid | 10 | 12074109 | A | G | – | 0.01 | 0.82 | 0.13 | 1.3E-10 | 3,12 |
| LMO1 | Threonine | 11 | 8255106 | G | A | rs204926 | 0.25 | −0.16 | 0.03 | 2.3E-10 | 3 |
| SAA1 | 2-Hydroxyisovaleric acid | 11 | 18338682 | A | C | rs10741740 | 0.56 | −0.22 | 0.02 | 1.8E-27 | 3,4,5,6,8,24,29 |
| EXT2 | Xylose | 11 | 44085687 | C | A | rs7127924 | 0.21 | 0.23 | 0.03 | 1.7E-19 | b |
| GLYAT | Acetylglycine | 11 | 58462882 | T | C | rs11229584 | 0.83 | 0.22 | 0.03 | 5.8E-15 | 3,13 |
| SLC22A12 | Uric acid | 11 | 64361219 | G | A | rs121907892 | 0.03 | −1.48 | 0.06 | 8.0E-130 | 11,13,31,36,37,40,41,46,50,53 |
| NOX4 | Cystine | 11 | 89224453 | A | C | rs2289125 | 0.52 | 0.21 | 0.02 | 4.3E-24 | 3 |
| PAH | Phenylalanine | 12 | 103306579 | C | T | rs118092776 | 0.04 | 1.04 | 0.05 | 7.7E-96 | 3,5,11,12,13,16,21,23,26 |
| ALDH2 | 2-Hydroxyisovaleric acid | 12 | 112230019 | G | C | rs4646776 | 0.27 | −0.24 | 0.02 | 1.2E-25 | b |
| 2-Oxoisocaproic acid | 12 | 112241766 | G | A | rs671 | 0.27 | −0.17 | 0.02 | 4.8E-14 | 11 | |
| HPD | 2-Hydroxyisobutyric acid | 12 | 122289655 | G | A | rs372273603 | 0.82 | 0.36 | 0.03 | 5.3E-41 | 5,59,60,65 |
| 3-Hydroxyisovaleric acid | 12 | 122303755 | C | T | rs2928283 | 0.23 | −0.19 | 0.02 | 5.6E-15 | 3,4,10 | |
| ASPG | Asparagine | 14 | 104561998 | T | C | rs1770983 | 0.87 | −0.34 | 0.03 | 2.2E-26 | 3,4,5,9,11,12,13,14,21,24 |
| ACSM2A | 3-Indolepropionic acid | 16 | 20466487 | T | G | rs117928765 | 0.17 | 0.35 | 0.04 | 2.3E-21 | 3,4,5,6,13,24,66 |
| ACSM2B | 3-Hydroxyisovaleric acid | 16 | 20563528 | T | C | rs77863699 | 0.20 | 0.37 | 0.03 | 1.4E-49 | 3,4,10,24 |
| GCSH | Glycine | 16 | 81147730 | C | T | rs4258631 | 0.79 | 0.19 | 0.03 | 8.2E-15 | 3,11,12,16,17,21,24,25,26,28 |
| SLC7A5 | Kynurenine | 16 | 87878076 | G | A | rs4843715 | 0.12 | 0.22 | 0.03 | 7.8E-13 | 3,4,5,6,12,13,24,57 |
| DPEP1 | Cystine | 16 | 89693149 | C | T | rs79068217 | 0.48 | 0.15 | 0.02 | 2.9E-12 | b |
| Hypotaurine | 16 | 89704365 | G | C | rs1126464 | 0.32 | 0.16 | 0.02 | 1.4E-11 | b | |
| Cysteinylglycine | 16 | 89722390 | G | A | rs164752 | 0.40 | 0.44 | 0.02 | 5.6E-101 | 3,4,10 | |
| SLC13A5 | Citric acid | 17 | 6619817 | T | C | rs170148 | 0.59 | 0.16 | 0.02 | 7.2E-11 | 5,11,26 |
| PRPSAP2 | 1,5-Anhydro-D-sorbitol | 17 | 18772654 | C | CT | rs11460734 | 0.25 | 0.17 | 0.02 | 3.1E-12 | 3,6,67 |
| DCXR | Ribulose | 17 | 79996451 | G | A | rs56001523 | 0.06 | −0.54 | 0.05 | 8.4E-32 | a |
| TYMS | Arabinonic acid | 18 | 680520 | A | C | rs7239738 | 0.40 | −0.31 | 0.02 | 6.6E-52 | 3 |
| CEP89 | Hypotaurine | 19 | 33423691 | T | A | – | 0.01 | −0.66 | 0.10 | 5.3E-11 | b |
| PRODH2 | 4-Hydroxyproline | 19 | 36290977 | C | T | rs3761097 | 0.16 | 0.29 | 0.03 | 6.2E-23 | 12 |
| Pipecolinic acid | 19 | 36290977 | C | T | rs3761097 | 0.16 | 0.45 | 0.03 | 2.7E-56 | b | |
| FUT2 | Fucose | 19 | 49206631 | A | T | rs1047781 | 0.41 | −0.85 | 0.02 | 9.2E-483 | 65 |
| TP53RK | 2-Oxoglutaric acid | 20 | 45236778 | T | C | rs6124830 | 0.46 | 0.17 | 0.02 | 3.7E-16 | b |
| PRODH | Proline | 22 | 18910844 | A | G | rs4269009 | 0.14 | 0.68 | 0.03 | 2.5E-119 | 3,4,5,6,8,11,12,13,14,17,21,22,23,24,29,30,68 |
| MPST | Creatinine | 22 | 37463858 | G | GCAAGGCCCTG TCTGCCATTCTG GTTGCTCCTCGC CCAAGGCCCTG TCTGCCATTCTG GTTGCTCCTCGCC |
– | 0.42 | −0.14 | 0.02 | 2.6E-10 | b |
Frequency and effect size are based on the ALT allele.
a
Metabolites for which QTL was found for the first time in this study.
b
Newly identified pair of locus and metabolite.
c
Metabolites associated with this gene have not been reported.
d
References are shown in supplemental information.