gene nlp trait rsid explanation explanation_source gwas_source annotation_source A4GALT 66.31184724440844 lactosyl-N-behenoyl-sphingosine (d18:1/22:0) rs200366907 A4GALT encodes a lactosylceramide 4-alpha-galactosyltransferase which adds a galactose moeity to a lactosylceramide molecule resulting in globotriaosylceramide (Gb3). The observed metabolite is a likely substrate. 10748143 35347128 35347128 AADAT 19.25 kynurenate rs6855450 AADAT encodes a mitochondrial kynurenine aminotransferase which can act directly on kynurenine, AADAT encodes a mitochondrial kynurenine aminotransferase which can act directly on kynurenine. Xanthurenate, another metabolite associated with this locus, is a metabolite of kynurenine. 2029638 36357675 36357675 ABCA1 64.825 HDL Cholesterol rs1883025 ABCA1 encodes a cholesterol transporter. Deficiency results in reduced HDL. 10431237 GLGC 30239796 ABCA7 66.32 palmitoyl sphingomyelin (d18:1/16:0)/lactosyl-N-palmitoyl-sphingosine rs1968456 ABCA7 encodes an ATP-binding cassette transporter that catalyzes sphingomyelin efflux to apoA-I. 12917409 36357675 36357675 ABCB11 11.398 Cholesterol, total rs2287623 ABCB11 encodes a transporter for taurocholate, a bile acid derived from cholesterol 1862084 24097068 30239796 ABCC1 67.69 5-oxoproline/cys-gly, oxidized rs60782127 ABCC1 encodes a transporter for glutathione, oxidized glutathione, glutathione conjugates and cysteinylglycine conjugates. The metabolite observed here, cys-gly, is related to these metabolites. 8640791 36357675 36357675 ABCC2 80.35 glycocholenate sulfate* rs113441420 ABCC2 encodes hepatobilliary transporter which can transport certain bile acids 11248200 36357675 36357675 ABCC3 24.51 5alpha-pregnan-3beta,20alpha-diol monosulfate (2)/pregnanediol-3-glucuronide rs11658264 ABCC3 encodes a liver-expressed transporter (MRP3) which can act on bile salts and glucuronide derivatives related to the metabolite observed here, glycochenodeoxycholate glucuronide. 10329726 36357675 36357675 ABCG2 218.17 4-hydroxychlorothalonil rs2231142 ABCG2 encodes ABC transporter with broad substrate specificity including many fungicides. Chlorothalonil is a fungicide and is conceivably a substrate for this transporter. It also has urate transport activity. 27288731|19506252 36357675 36357675 ABCG5|ABCG8 36.56815395430127 campesterol rs6544713 ABCG5 and ABCG8 together encode a heterodimeric ATP-dependent transmembrane sterol transporter 14504269 35347128 35347128 ABHD12 18.16 1-stearoyl-2-arachidonoyl-GPI (18:0/20:4)/1-palmitoyl-2-arachidonoyl-GPI (16:0/20:4)* rs11474922 ABHD12 encodes a monoacylglycerol lipase; lysophosphatidylinositol can be converted to monoacylglycerol through the action of a lysophosphoinositide-specific phospholipase C. 22969151|7893146 36357675 36357675 ABHD2 10.03 1-linoleoyl-2-arachidonoyl-GPC (18:2/20:4n6)* rs73467771 ABHD2 encodes an arachidonoylglycerol hydrolase. The observed metabolite is a related molecule, a glycerophosphocholine with one chain of arachidonic acid at the C-2 position. 26989199 36357675 36357675 ABHD3 31.550984683652214 1-myristoyl-2-linoleoyl-GPC (14:0/18:2) rs181026394 ABHD3 encodes a phospholipase with demonstrated activity against PC(32:2), specifically the PC(14:0|18:2) stereoisomer. 21926997 35347128 35347128 ABO 36.046 Blood metabolite ratios (ADSGEGDFXAEGGGVR/ADpSGEGDFXAEGGGVR) rs649129 ABO encodes a glycosyltransferase that determines the blood group. ABO blood group contributes to von Willebrand Factor levels perhaps by protecting it from susceptibility to ADAMTS13-mediated proteolysis. As part of the coagulation cascade, von Willebrand Factor effects rates of fibrinogen cleavage. 17894864 24816252 30239796 ACAD8 198.55 isobutyrylcarnitine/propionylcarnitine rs113488591 ACAD8 encodes an acyl-CoA dehydrogenase with specific activity toward isobuteryl-CoA, which is readily converted to isobutyrylcarnitine. Rare disease results in elevated isobutyrylcarnitine levels, ACAD8 encodes an acyl-CoA dehydrogenase with specific activity toward isobuteryl-CoA, which is readily converted to isobutyrylcarnitine which can then be converted to isobutyrylglycine 12359132 36357675 36357675 ACADL 134 Blood metabolite levels (X-13431--nonanoylcarnitine) rs3738934 ACADL encodes Long-chain acyl-CoA dehydrogenase which has activity against a variety of medium and long chain acyl-CoAs . Intracellular acyl-CoAs are converted to acyl-carnitines for circulation. 10832093 24816252 30239796 ACADM 565.68 octanoylcarnitine/laurylcarnitine rs145024038 ACADM encodes an acyl-CoA dehydrogenase with a preference for medium chain length acyl-CoAs. Acyl-CoAs are converted to acyl-carnitines for circulation which are then detected in the plasma. 3597357 36357675 36357675 ACADS 2295.05 ethylmalonate/pseudouridine rs2014355 ACADS encodes the short chain acyl-CoA dehydrogenase which takes butyrl-CoA as a substrate. Butyryl-CoA and butyrylcarnitine readily interconvert. 3597357 36357675 36357675 ACADVL 47.45 octanoylcarnitine/myristoleoylcarnitine* rs534908188 ACADVL encodes acyl-CoA dehydrogenase very long chain which 1730632 36357675 36357675 ACE 37 Blood metabolite ratios (aspartylphenylalanine/X-14450--phenylalanylleucine) rs4343 ACE encodes an angiotensin-converting enzyme. This carboxypeptidase can generate aspartylphenylalanine from cholecystokinin-8. 2554881 24816252 30239796 ACMSD 21.431329021990102 N1-Methyl-2-pyridone-5-carboxamide rs17322446 ACMSD encodes alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase, the key enzyme regulating de novo synthesis of nicitinamide adenine dinucleotide (NAD) from tryptophan. The associated metabolites are involved in nicotinamde metabolism. 16807375|12694300 35347128 35347128 ACOT1|ACOT2|ACOT4|ACOT6 400.92445303860745 decadienedioic acid (C10:2-DC) rs11626972 ACOT1|ACOT2|ACOT4|ACOT6 encode a family of Acyl-CoA thioesterases which catalyze the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A 16940157 35347128 35347128 ACOT7 20.79 3-hydroxyoctanoate rs146144846 ACOT7 encodes a long chain acyl-CoA thioester hydrolase which can act on octanoyl-CoA, releasing octanoate which is related to the observed metabolite 3-hydroxyoctanoate. 10578051 36357675 36357675 ACOX1 31.85 adipoylcarnitine rs56291490 ACOX1 encodes a peroxisomal acyl-CoA oxidase which introduces a double bond into the fatty acid moeity of an acyl-CoA. Adipoylcarnitine, the metabolite observed here, is likely derived from an acyl-CoA which may be a substrate for the enzyme or may be related to a substrate. 8117268 36357675 36357675 ACSF3 145.89756629431866 methylmalonate (MMA) rs72817438 ACSF3 encodes a malonyl-CoA synthase. Rare disease results in combined malonic and methylmalonic aciduria 21846720 35347128 35347128 ACSL1 10.475 PC ae C44:5 rs7700133 ACSL1 encodes a long-chain fatty-acid-coenzyme A ligase which produces acyl-CoAs. These in turn can be used in the synthesis of plasmalogens, e.g., via LPCAT4 8584017 26068415 30239796 ACSM1|ACSM2A|ACSM2B|ACSM3|ACSM5 22.41 beta-hydroxyisovalerate rs145821719 ACSM1/ACSM2A/ACSM2B/ACSM3/ACSM5 encode a set of paralogous medium chain length acyl-coenzyme A synthetases with similar substrate specificity. Any of them could potentially act on the observed metabolite. 36357675 36357675 ACSM6 19.74 3-hydroxy-2-ethylpropionate rs34576142 ACSM6 encodes a protein with 50% sequence identity to known medium chain length acyl-CoA synthetases. The associated metabolite could be a substrate for this enzyme no suitable citation 36357675 36357675 ACY1 210.75 N-acetylalanine rs121912698 ACY1 encodes an aminoacylase which specifically hydrolyzes acylated amino acids. Rare disease results in increased urine levels of N-acetylated amino acids. Acetylmethionine is a substrate for the aminoacylase. 18222180 36357675 36357675 ACY3 99.24 N-acetyltryptophan rs948445 ACY3 encodes an aminoacylase which preferentially deacetylates N-acetylaromatic amino acids including N-acetyl-L-phenylalanine. 14656720 36357675 36357675 ADA 30.16 N1-methyladenosine rs6103815 ADA encodes adenosine deaminase which converts adenosine to inosine. The observed metabolite at this locus, N1-methyladenosine, is derived from adenosine. 16747549 36357675 36357675 ADH1A|ADH1B|ADH1C|ADH4|ADH5|ADH6|ADH7 26.549289121853082 gluconate rs138883026 ADH1A|ADH1B|ADH1C|ADH4|ADH5|ADH6|ADH7 encode a set of alcohol dehydrogenases which convert a free alcohol group to an aldehyde. The observed metabolite, gluconate, has multiple alcohol groups and represents a potential substrate 33415501 35347128 35347128 ADHFE1 11 Blood metabolite levels (X-04499--3,4-dihydroxybutyrate) rs1030420 ADHFE1 encodes the hydroxyacid-oxoacid transhydrogenase which catalyzes the oxidation of 4-hydroxybutanoic acid to 4-oxobutanoic acid, while reducing 2-oxoglutarate to 2-hydroxyglutarate. 16616524 24816252 30239796 ADSL 50.78 O-sulfo-L-tyrosine/N6-succinyladenosine rs8135371 ADSL encodes adenylosuccinate lyase which converts adenylosuccinate to adenosine monophosphate. N6-succinyladenosine, the metabolite observed at this locus, is the dephosphorylated version of the substrate adenylosuccinate. Rare loss of function of this enzyme results in elevated circulating levels of N6-succinykladenosine. 5432795 36357675 36357675 AFMID 217.02017856996977 N-formylanthranilic acid rs77585764 AFMID encodes arylformamidase which can act on the metabolite observed here, n-formylanthranilic acid 14794728 35347128 35347128 AGA 106.52 aspartate/asparagine rs13149149 AGA encodes the enzyme aspartylglucosaminidase which generates asparagine from N-acetylglucosamines. Deficiency results in an accumulation of asparagine-linked glycopeptides. 1281977 36357675 36357675 AGMAT 372.32 4-guanidinobutanoate/methionine sulfoxide rs34098917 AGMAT encodes agmatinase which converts agmatine to putrescine. Agmatine itself is derived from arginine. The observed metabolite, 4-guanidinobutanoate, is an alternate derivate of arginine. 8858963 36357675 36357675 AGPAT1 71.18 1-palmitoyl-2-oleoyl-GPC (16:0/18:1)/1,2-dipalmitoyl-GPC (16:0/16:0) rs1061808 AGPAT1 encodes 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha, an enzyme which produces phosphatidic acid. 17707131 36357675 36357675 AGPAT2 13.72 1-docosapentaenoyl-GPC (22:5n3)* rs2236514 AGPAT2 encodes a lysophosphatidic acid acyltransferase which acts on lysolipids related to the metabolite observed here. 21873652 36357675 36357675 AGPAT3 8.47 1-docosapentaenoyl-GPC (22:5n3)* rs62229686 AGPAT3 encodes a lysophosphatidic acid acyltransferase which converts a lysolipid to phospholipid which shows activity against lysophosphatidylcholines similar to the metabolite observed at this locus, 1-docosapentaenoyl-GPC. 21173190 36357675 36357675 AGPS 9.39 PC ae C44:5 rs7582179 AGPS encodes the alkylglycerone phosphate synthase which generates ether phospholipids such as the metabolite detected here. 10215861 26068415 30239796 AGXT 17.159 alpha-ketoisovalerate|urine rs6748734 AGXT encodes alanine-glyoxylate aminotransferase. When acting on valine, rather than alanine, as a substrate, the enzyme will produce alpha-ketoisovaleric acid as a product (see EC code EC 2.6.1.66). The mouse and rat orthologs have demonstrated activity on valine. 629740 26352407 30239796 AGXT2 859.99 3-aminoisobutyrate/creatinine rs37370 AGXT2 encodes an alanine-glyoxylate aminotransferase, an enzyme which can take 3-aminoisobutyrate as a substrate. 8427875|5773299 36357675 36357675 AHR 62.91 7-methylxanthine/theobromine rs6968865 AHR encodes the aromatic hydrocarbon receptor, a transcription factor which activates CYP1A1 and CYP1A2. These enzymes metabolize caffeine, leading to the metabolites associated with this locus. Variants at CYP1A2 are associated with these same metabolites. 10605936|8095225 36357675 36357675 AKR1A1 122.76548271648731 ribitol rs2229540 AKR1A1 encodes an aldehyde reductase which can catalyze the production of erythritol, one of the metabolites associated with this variant. 4402936 35347128 35347128 AKR1C1|AKR1C2|AKR1C3|AKR1C4 132.61 epiandrosterone sulfate/5alpha-androstan-3alpha,17alpha-diol monosulfate rs146562425 AKR1C4 encodes a 3 alpha-hydroxysteroid dehydrogenase (HSD) isoform, which is expressed in the liver and acts on androsterone. The nearby paralogous gene AKR1C3 is expressed in prostate and mammary gland and the encoded enzyme does not act on androsterone. 15026176 36357675 36357675 AKR1D1 16.12 etiocholanolone glucuronide rs112737566 AKR1D1 encodes a steroid 5beta-reductase which reduces the double bond between the 4 and 5 carbon positions in the steroid backbone of many human metabolites including androst-4-ene-3,17-dione, generating 5beta-androstane-3,17-dione, also known as etiocholanedione. This is then converted to etiocholanolone, which is then glucuronidated for elimination, producing the named metabolite observed at this locus. 11342103 36357675 36357675 AKT1 8.019 HDL Cholesterol rs4983559 AKT1 encodes a protein kinase which activates SREBP which induces transcription of enzymes involved in cholesterol biosynthesis. 16007182 GLGC 30239796 ALAD 13.398 Lead levels in blood rs1805313 ALAD encodes aminolevulinate dehydratase, an enzyme which binds to lead. 1713045 25820613 30239796 ALDH18A1 10.097 Blood metabolite levels (citrulline) rs56322409 ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthetase which catalyzes a step in the de novo production of ornithine which is subsequently converted to citrulline. Mutations in ALDH18A1 cause hypocitrullinemia. 11092761 24816252 30239796 ALDH1L1 26.5 serine/glycine rs10934753 ALDH1L1 encodes the formyltetrahydrofolate dehydrogenase which converts formyltetrahydrofolate to tetrahydrofolate as part of the one carbon metabolism cycle. Glycine can be used to rechard tetrahydrofolate to methylenetetrahydrolate via glycine dehydrogenase (GLDC). 7702556|4585091 36357675 36357675 ALDH4A1 35.036212172654444 S-1-pyrroline-5-carboxylate rs61757683 ALDH4A1 encodes delta-1-pyrroline-5-carboxylate dehydrogenase which converts pyrroline-5-carboxylate to glutamate in the breakdown of proline. 2211729 35347128 35347128 ALDH7A1 71.65227978296596 6-oxopiperidine-2-carboxylate rs79449010 ALDH7A encodes an aldehyde dehydrogenase which produces alpha-aminoadipic acid in the pipecolic acid pathway of lysine catabolism. Alpha-aminoadipic acid can be cyclized to form the observed metabolite, 6-oxopiperidine-2-carboxylic acid, although the exact mechanism in humans in unknown. 16491085|9544928 35347128 35347128 ALOX12 22.699 Blood metabolite levels (X-12441--12-hydroxyeicosatetraenoate (12-HETE)) rs2271316 ALOX12 encodes arachidonate 12-lipoxygenase, which catalyzes the regio-selective addition of oxygen into arachidonic acid, generating 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). 12R-HPETE is rapidly reduced to the corresponding 12S-hydroxy compound, 12-HETE. 4215079, 2377602 24816252 30239796 ALOX5 12.038531444649214 arachidonoylcarnitine (C20:4) rs71515366 ALOX5 encodes arachidonate 5-lipoxygenase, which adds oxygen to arachidonate and related fatty acids. arachidonoylcarnitine is derived from arachidonate. 6432877 35347128 35347128 ALPL 37.29 choline phosphate rs4654748 ALPL encodes the liver alkaline phosphatase. Loss of function of alkaline phosphatase causes hypophosphatasia. 3174660 36357675 36357675 AMDHD1 8.98 hydantoin-5-propionic acid rs4762256 AMDHD1 encodes an imidazolonepropionase (EC 3.5.2.7) which converts 4-Imidazolone-5-propanoate to N-formimino-L-glutamate. The former metabolite can also be converted to the metabolite observed here, hydantoin-5-propionate. 13914653 36357675 36357675 AMPD2 99.57 3,7-dimethylurate/7-methylxanthine rs36209093 AMPD2 encodes liver paralog of AMP deaminase which converts AMP to IMP. 3,7-dimethylurate is a closely related metabolite and may be a downstream metabolite of IMP. 14081922 36357675 36357675 ANGPTL3 81.456 Triglycerides rs4587594 ANGPTL3 encodes a protein that regulates triglyceride clearance by reducing the activity of lipoprotein lipase (LPL). 22063269 GLGC 30239796 ANGPTL4 36.538 Triglycerides rs116843064 ANGPTL4 regulates TG clearance by reducing the activity of LPL 16081640 24507774 30239796 ANGPTL8 9.09 1-stearoyl-2-arachidonoyl-GPI (18:0/20:4) rs66466742 ANGPTL8 encodes angiopoietin like 8 which works with angiopoietin like 3 (ANGPTL3) to inhibit lipoprotein lipase (LPL) and triglyceride clearance. This then influences levels of other specific lipid species. 28413163|22063269|13712364 36357675 36357675 ANPEP 11.531357331608488 phenylalanylphenylalanine rs28463231 ANPEP encodes Aminopeptidase N, which is a broad specificity aminopeptidase. 7957888|9647737 35347128 35347128 AOC1 49.984640244590786 (N(1) + N(8))-acetylspermidine rs7794796 AOC1 encodes an amine oxidase which deaminates N1-acetylspermidine to produce N-[3-(2-oxopyrrolidin-1-yl)propyl]acetamide (also known as acisoga). 12072962 35347128 35347128 AOX1 20.32 7-methylguanine rs55754655 AOX1 encodes an aldehyde oxidase which can act on many substrates including purines. Activity against the observed metabolite, 7-methylguanine, has been reported. 5044040 36357675 36357675 APOA1|APOA4|APOA5|APOC3 43.82 1-oleoyl-2-linoleoyl-glycerol (18:1/18:2) rs964184 The APOA5/APOA4/APOA1/APOC3 gene cluster encodes a set of related apolipoproteins involved in trafficking of apolipoprotein particles. This influences abundance and distribution of a multitude of lipid species. 36357675 36357675 APOA2 10.495 XL.HDL.PL rs4503368 APOA2 encodes apolipoprotein A-II, a major component of HDL particles 24089247 27005778 30239796 APOB 182.023 LDL Cholesterol rs1367117 APOB encodes apolipoprotein B, a major component of LDL particles. Defects in APOB can lead to familial hypercholesterolemia. 52771 GLGC 30239796 APOC1|APOC2|APOC4|APOE 41.79 cholesterol/1-(1-enyl-stearoyl)-2-linoleoyl-GPE (P-18:0/18:2)* rs7412 APOE/APOC1/APOC2/APOC4 encode a set of related apolipoproteins involved in lipoprotein particle trafficking. Any or all of them could be influencing levels of various lipid species. 36357675 36357675 APOH 11.008 LDL Cholesterol rs1801689 ApoH increases the enzymic activity of lipoprotein lipase (LPL) in the presence of apoC-II by 45.7 percent [ 7417307]. a small molecule inhibitor of PKC alpha, HBDDE, show minimal inhibition of cholesterol accumulation while a small molecule inhibitor of PKC beta, LY333513, could completely account for the inhibition of cholesterol accumulation by the classical group PKC isoenzyme [16930534] 7417307 GLGC 30239796 AQP10 21.06 arabonate/xylonate rs6685323 AQP10 encodes an aquaglyceroporin which transports water and glycerol and larger molecules including xylitol. 21733844 36357675 36357675 ARG1 43.65 arginine rs17788484 ARG1 encodes an arginase which hydrolyzes arginine. Enzyme deficiency causes argininemia. 3540966 36357675 36357675 ARSA 54.37 O-sulfo-L-tyrosine/pseudouridine rs6151429 ARSA encodes the arylsulfatase A, which can act on L-tyrosine O-sulfate. 33715 36357675 36357675 ARSD|ARSL 48.19873352951038 ascorbic acid 3-sulfate rs1637781 ARSD|ARSL encode a pair of aryl sulfatases. The homologs ARSA and ARSB act on ascorbic acid 2-sulfate. Ascorbic acid 3-sulfate is a plausible substrate for one or both proximal enzymes. 28257906|33715 35347128 35347128 AS3MT 8.523 Arsenic metabolism (DMA%) rs9527 AS3MT encodes arsenite methyltransferase which acts on methylarsonite to produce dimethylarsinate (also known as cacodylate) 20621156 22383894 30239796 ASPG 230.99 glutamine/asparagine rs8012505 ASPG encodes an asparaginase homolog which which can hydrolyse asparagine to form aspartic acid. 9575212 36357675 36357675 ASRGL1 14.742561433140187 asparagine rs138510246 ASRGL1 encodes an asparaginase which hydrolyzes asparagine to produce aspartate. 24768817 35347128 35347128 ASS1 23.3 citrulline rs7870202 ASS1 encodes argininosuccinate synthase takes citrulline as a substrate. 6194510 36357675 36357675 ATP10A 10.38 1-(1-enyl-palmitoyl)-2-oleoyl-GPC (P-16:0/18:1)* rs11161244 ATPA10 encodes a phospholipid flippase with specific activity towards phosphatidylcholine. 25947375 36357675 36357675 ATP10D 152.61 palmitoyl sphingomyelin (d18:1/16:0)/glycosyl-N-palmitoyl-sphingosine rs35818294 ATP10D encodes a phospholipid flippase. Closely related gene family members have demonstrated activity versus phosphatidylcholine. 25947375 36357675 36357675 BBOX1 23.11 deoxycarnitine rs201184146 BBOX1 encodes gamma-butyrobetaine hydroxylase which converts the observed metabolite, deoxycarnitine (also known as gamma-butyrobetaine) into carnitine. 7156861 36357675 36357675 BCAT1 60.15 4-methyl-2-oxopentanoate/3-methyl-2-oxobutyrate rs11047635 BCAT1 encodes a branched chain amino acid transaminase which converts each of the three branched chain amino acids into the corresponding branched chain keto acids. 4-methyl-2-oxopentanoate is the product of the transamination of leucine. Rare disease results in elevated levels of all 3 branched chain amino acids 641889 36357675 36357675 BCAT2 8.46 valine rs4801776 BCAT2 encodes a branched chain amino acid transaminase which converts each of the three branched chain amino acids into the corresponding branched chain keto acids. Valine is a substrate of the enzyme. Rare disease results in elevated levels of all 3 branched chain amino acids. 641889 36357675 36357675 BCO1 121.61996975203218 carotene diol (1) rs11643509 BCO1 (previously referred to as BCMO1) encodes beta-carotene oxygenase 1 which uses a molecule of oxygen to produce two molecules of retinol from beta-carotene. Enzyme deficiency results in accumulation of beta-carotene. 11401432 35347128 35347128 BHMT|DMGDH 184.17 dimethylglycine/phenylalanine rs145258663 DMGDH encodes dimethylglycine dehydrogenase which takes dimethlyglycine as a substrate. Enzyme deficiency results in excess dimethlyglycine. 10102904 36357675 36357675 CASR 85.046 Calcium levels rs1801725 CASR encodes the calcium sensing receptor, a GPCR which binds calcium and regulates parathyroid hormone secretion which in turn regulates circulating levels of calcium. 11013439 24068962 30239796 CAV1 7.676 Triglycerides rs38855 CAV1 encodes caveolin-1, a scaffolding protein. Very rare CAV1 frameshift mutations appear to be associated with atypical lipodystrophy and hypertriglyceridemia. 18237401 GLGC 30239796 CBS 25.523 Plasma homocysteine levels (post-methionine load test) rs234714 CBS encodes the cystathionine beta-synthase which acts on homocysteine to produce cystathionine 16545978 24651765 30239796 CD36 9.222 HDL cholesterol (AA) rs2366858 CD36 encodes a platelet glycoprotein which binds HDL 9867808 23726366 30239796 CDA 17.82 uridine rs66731853 CDA encodes cytidine deaminase which deaminates cytidine, producing uridine, the metabolite observed here. 8422236 36357675 36357675 CDO1 11.49 hypotaurine rs12651799 CDO1 encodes cysteine dioxygenase which catalyzes the first step in the conversion of cysteine to the observed metabolite, hypotaurine. 2307 36357675 36357675 CERS1 105.66394072213365 glycosyl-N-stearoyl-sphingosine (d18:1/18:0) rs1013893365 CERS1 encodes a ceramide synthase with specificity for C18 fatty acids. Sphingomyelins can be synthesized from ceramides. 12105227 35347128 35347128 CERS4 176.85 palmitoyl sphingomyelin (d18:1/16:0)/sphingomyelin (d18:1/20:1, d18:2/20:0)* rs922442 CERS4 encodes a ceramide synthase which produces ceramides from sphingosine and a long chain acyl CoA, derived from long chain free fatty acids. 12912983 36357675 36357675 CERS5 8.05 sphingomyelin (d18:2/14:0, d18:1/14:1)* rs143955263 CERS5 encodes a ceramide synthase which creates a palmitate-containing ceramide. The ceramides are metabolically related to sphingomyelin. 16100120 36357675 36357675 CETP 801.939 HDL Cholesterol rs247616 CETP encodes the cholesterol ester transfer protein which acts on high density lipoprotein (HDL). Deficiency of this enzyme results in increased HDL. 2586614 GLGC 30239796 CHKA 15.014932966849498 choline phosphate rs7940113 CHKA encodes choline kinase. The observed metabolite, choline phosphate, is the product of the reaction. 4373031 35347128 35347128 COMT 184.7632109005907 2-O-methylascorbic acid rs4680 COMT encodes the catechol-O-methyltransferase which can methylate L-dopa to produce the metabolite observed here, 3-methoxytyrosine. 13575440 35347128 35347128 CPS1 564.84 glutamine/glycine rs1047891 CPS1 encodes a mitochondrial carbamoyl phosphate synthetase which takes ammonia as a substrate. Glycine and ammonia are interconverted via the glycine cleavage complex. 18941301 36357675 36357675 CPT1A 42.196201592010325 cerotoylcarnitine (C26) rs189174414 CPT1A encodes a carnitine O-palmitoyltransferase 1865762 35347128 35347128 CPT2 157.11 adipoylcarnitine/glutarylcarnitine (C5) rs1134688 CPT2 encodes carnitine palmitoyltransferase II, which catalyzes the transfer of palmitate and related metabolites from carnitine to coenzyme A in the mitochondrial inner membrane. 9654057 36357675 36357675 CRAT 82.375 Methylmalonylcarnitine rs746872 CRAT encodes carnitine O-acetyltransferase, which catalyzes the interconversion of short chain acylcarnitines and acyl-coenzyme A derivatives. 2351134 26401656 30239796 CRYL1 12.37706103078851 mannonate rs9552189 CRYL1 encodes an enzyme with gulonate dehydrogenase activity. Mannonate is a closely related molecule and potential substrate. 15809331 35347128 35347128 CSAD 9.4 hypotaurine rs149264090 CSAD encodes cysteine sulfinic acid decarboxylase which produces the metabolite observed here, hypotaurine. 11997111 36357675 36357675 CTH 137.6 cystathionine/gamma-glutamylphenylalanine rs28941785 CTH encodes cystathionine gamma-lyase which produces cysteine from cystathionine 10212249 36357675 36357675 CUBN 12.699 Vitamin B levels in ischemic stroke (Vitamin B12) rs1801222 CUBN encodes cubilin, a protein involved in the uptake of vitamin B12 (cobalamin). CUBN deficiency results in reduced levels of cobalamin. 9478979 25147783 30239796 CYP3A4|CYP3A43|CYP3A5|CYP3A7 2287.58 androsterone sulfate/16a-hydroxy DHEA 3-sulfate rs45446698 These three paralogs encode cytochrome P450 enzymes, all of which can act on testosterone and other metabolites related to the observed metabolites 36357675 36357675 D2HGDH 64.9519468268844 2-hydroxyglutarate rs146578303 D2HGDH encodes a D-2-hydroxyglutarate dehydrogenase which takes 2-hydroxyglutarate as a substrate. The observed metabolite, 2-hydroxybutyrate, is a closely related metabolite. 7564244 35347128 35347128 DBH 14.746904414150968 vanillylmandelate (VMA) rs77273740 DBH encodes the copper-containing dopamine beta-hydroxylase which converts dopamine to noradrenaline, a precursor for vanillylmandelate, the metabolite observed here. It's also possible the observed metabolite could be a product of this enzyme acting on homovanillate. The ratio of these two metabolites is a biomarker for dopeamine beta-hydroxylase activity. 14253475|15702409 35347128 35347128 DCXR 7.34 arabitol/xylitol rs72861739 DCXR encodes a xylulose reductase which interconverts xylitol and xylulose 11882650 36357675 36357675 DDAH1 40 Serum dimethylarginine levels (asymmetric) rs28489187 DDAH1 encodes dimethylarginine dimethylaminohydrolase which acts directly on dimethylarginine. 7608105 24159190 30239796 DDC 46.89 3-methoxytyrosine/indoleacetate rs930707 DDC encodes dopa decarboxylase which converts tryptophan to tryptamine, which can be further metabolized to indoleacetic acid. 13610897 36357675 36357675 DEGS1 28.35 palmitoyl dihydrosphingomyelin (d18:0/16:0)*/palmitoyl sphingomyelin (d18:1/16:0) rs145711419 DEGS1 encodes sphingolipid delta 4-desaturase which introduces a double bond at the 4 position in sphingomyelin. The observed metabolite, palmitoyl dihydrosphingomyelin, should be a substrate for this enzyme. 11937514 36357675 36357675 DGAT2|MOGAT2 29.38 1-dihomo-linolenoyl-GPC (20:3n3 or 6)*/1-palmitoyl-2-linoleoyl-GPE (16:0/18:2) rs559355 DGAT2 and MOGAT2 are both liver enriched enzymes involved in triglyceride metabolism. Both could influence lipid metabolism in general including the metabolites observed here. 36357675 36357675 DHCR7 26.699 Vitamin D insufficiency rs12785878 DHCR7 encodes 7-dehydrocholesterol reductase, which acts on 7-dehydrocholesterol, a precursor of vitamin D. 10807690 20541252 30239796 DHDH 11.70730099695607 arabinose rs35230038 DHDH encodes dihydrodiol dehydrogenase which can oxidize the observed metabolite, arabinose, generating the corresponding lactone. 11306093 35347128 35347128 DHTKD1 45.471597562046384 1-ribosyl-imidazoleacetate rs7094385 DHTKD1 encodes an enzyme which decarboxylates 2-oxoadipate and produces glutaryl-CoA. 23141293 35347128 35347128 DIO1 31.097 Thyroid hormone levels (FT4: free thyroxine) rs2235544 DIO1 encodes an iodothyronine deiodinase which deiodinates of thyroxine (T4) to produce the biologically active hormone T3 1400883 23408906 30239796 DPEP1 130.94 sphingosine 1-phosphate/cys-gly, oxidized rs409170 DPEP1 encodes a dipeptidase that acts on glutathione, which is a downstream product of homocysteine metabolism. Glutathione and homocysteine levels have been shown to be negatively correlated. 6122685 36357675 36357675 DPYD 147.23232477597205 uracil rs3918290 DPYD encodes dihydropyrimidine dehydrogenase which catalyzes the first step in the breakdown of uracil, the metabolite observed here. 8083224 35347128 35347128 ECHDC1 63.22 ethylmalonate/butyrylcarnitine rs189702295 ECHDC1 encodes ethylmalonyl-CoA decarboxylase converts ethylmalonyl-CoA to butyryl-CoA. 22016388 36357675 36357675 ECI1 13.677160727313678 dodecadienoate (12:2) rs55650311 ECI1 encodes an enoyl-CoA delta isomerase which exchanges a double bond at the 3 position for one at the 2 position in CoA bound fatty acids with demonstrated activity on C12 enoyl-CoA. Dodecadienoate is likely derived from a product of this reaction. 8486162 35347128 35347128 ECI2 37.398 Blood metabolite levels (X-13435, a 10:1 acylcarnitine) rs9392556 ECI2 encodes the enoyl-CoA delta isomerase 2, which is known to act on octenoyl-CoA and could possibly act on decenoyl-CoA as well. 10419495 24816252 30239796 ELOVL2 72.5 1-stearoyl-2-docosapentaenoyl-GPC (18:0/22:5n3)*/1-stearoyl-2-docosahexaenoyl-GPC (18:0/22:6) rs2208338 ELOVL2 encodes a long chain fatty acid elongase which acts specifically on very long chain fatty acids such as those observed at this locus. 12371743 36357675 36357675 ELOVL7 19.87 1-stearoyl-GPC (18:0)/1-arachidoyl-GPC (20:0) rs4482855 ELOVL7 encodes a fatty acid elongase with highest activity against 18 carbon and 20 carbon fatty acid chains such as those found associated at this locus either singly or in the metabolite ratio. 21959040 36357675 36357675 ENOSF1 30.55 ribonate rs10502289 ENOSF1 encodes a dehydratase which acts on a number of related sugar acids including ribonate, the metabolite observed at this locus. 24697329 36357675 36357675 ENPP6 19.66 choline phosphate rs78293932 ENPP6 encodes a glycerophosphocholine cholinephosphodiesterase which specifically hydrolyzes lysophosphatidylcholines to form a monoacylglycerol and choline phosphate, the metabolite observed here. 15788404 36357675 36357675 ETFA 30.48 isobutyrylcarnitine/propionylcarnitine rs2959850 ETFA encodes a mitochondrial-specific electron transfer flavoprotein. Enzyme deficiency results in urinary excretion of isobutyric acid and isobutyrylglycine; the urinary levels of these metabolites should reflect plasma levels of the analyte reported here, isobutyrylcarnitine., ETFA encodes a mitochondrial-specific electron transfer flavoprotein. Enzyme deficiency results in urinary excretion of isobutyric acid and isobutyrylglycine 7360517 36357675 36357675 ETFDH 38.04 octanoylcarnitine rs67481496 ETFDH encodes a mitochondrial electron transfer flavoprotein dehydrogenase which is essential for electron transfer from the short-, medium- and long-chain acyl-CoA dehydrogenases. Mutations in ETFDH lead to multiple acyl-CoA dehydrogenase deficiency, which is characterized by elevated short-, medium- and long-chain acyl carnitines. 17412732 36357675 36357675 ETNPPL 27.146 ethanolamine|urine rs56043887 ETNPPL encodes the ethanolamine-phosphate phospho-lyase which acts on the phosphorylated form of ethanolamine. AGXT2L1 is a common synonym for this gene. 22241472 26352407 30239796 F12 25.222 Blood metabolite ratios (X-12038/bradykinin, des-arg(9)) rs2731672 F12 encodes coagulation factor XII, a protease which activates kallikrein which releases bradykinin from kininogen. 3521732 24816252 30239796 F3 51.222 D-dimer levels rs12029080 F3 encodes coagulation factor 3, also known as tissue factor, which is involved in the initiation of the clotting cascade, which eventually results in the production of fibrin. The D-dimer metabolite is a degredation product of fibrin clots. 12223078 21502573 30239796 F5 13.699 D-dimer levels rs6687813 F5 encodes coagulation factor 5, an essential element of the clotting cascade, which eventually results in the production of fibrin. The D-dimer metabolite is a degredation product of fibrin clots. 25231258 21502573 30239796 FAAH 181.06 oleoyl ethanolamide/2-hydroxypalmitate rs570404435 FAAH encodes fatty acid amide hydrolase which can take the observed metabolite as a substrate. 17015445 36357675 36357675 FADS1 360.699 Blood metabolite ratios (arachidonate (20:4n6)/dihomo-linolenate (20:3n3 or n6)) rs174548 FADS1 encodes a delta-5 desaturase, which converts dihomo-linolenate (20:3n6) to arachidonate (20:4n6). 10601301 24816252 30239796 FADS1|FADS2 594.51 1-stearoyl-2-arachidonoyl-GPC (18:0/20:4) rs174564 FADS1 and FADS2 encode a pair of fatty acid desaturase which act on a number of related fatty acids. Either or both could be impacting the lipid species associated with this locus. 10860662 36357675 36357675 FDX1 106.45842075605341 3beta-hydroxy-5-cholestenoate rs2724417 FDX1 encodes ferredoxin 1 which is involved in electron transport for multiple cytochrome P450 enzymes, including CYP27A1 which plays a key role in bile acid biosynthesis which leads to the metabolites observed at this locus. 2340092 35347128 35347128 FGF23 8.398 Phosphorus levels rs2970818 FGF23 encodes a fibroblast growth factor which regulates phosphate levels through multiple mechanisms, including regulation of levels of kidney phosphate transporters 15863037 20558539 30239796 FGF9 14.54 dehydroisoandrosterone sulfate (DHEA-S) rs9509847 FGF9 encodes a fibroblast growth factor which is expressed in Sertoli cell and is important in the development of testes. The metabolite observed here, dehydroisoandrosterone sulfate, is derived from dehydroisoandrosterone (DHEA) which is produced in testes. 11290325 36357675 36357675 FGGY 11.38 ribitol rs62623594 FGGY encodes FGGY carbohydrate kinase which can phosphorylate the observed metabolite. Ribitol. 27909055 36357675 36357675 FMO1|FMO2|FMO3|FMO4 74.08 S-methylcysteine rs909530 FMO3 encodes a flavin containing monooxygenase which can act on S-allyl-cysteine and methionine. Methylcysteine is a plausible substrate. This isozyme prefers smaller substrates and shows highest expression in liver. 18775983 36357675 36357675 FOLH1 56.82419836715172 N-acetyl-aspartyl-glutamate (NAAG) rs10839234 FOLH1 encodes a dipeptidase that specifically hydrolyzes n-acetyl-aspartyl-glutamate, the metabolite observed here. 3346674 35347128 35347128 FOLH1B 19.699 Homocysteine levels rs7130284 FOLH1B encodes a liver-enriched polyglutamylfolate hydrolase which will influence folate availability for the conversion of homocysteine to methionine 9816319 23824729 30239796 FOXA2 11.719 Fasting plasma glucose (East Asian) rs6048216 FOXA2 encodes a transcription factor that impacts the expression of many genes (i.e., GCK, SLC2A2) previously related to the glucose levels. 11875061 25187374 30239796 FOXE1 10.699 Thyroid hormone levels (FT4: free thyroxine) rs7045138 FOXE1 encodes a transcription factor expressed specifically in thyroid gland, the source of the thyroxine (FT4 thyroid hormone) 9214635 23408906 30239796 FTCD 12.395665926897088 formiminoglutamate rs398124234 FTCD encodes a glutamate formimidoyltransferase which transfers one-carbon units between glutamate and folate. The metabolite seen here, forminoglutamate, can be both a substrate and a product for this enzyme. 13672973 35347128 35347128 FUT2 35.523 Urinary metabolites (H-NMR features) (5.2125, Fucose) rs2287921 FUT2 encodes a galactoside 2-alpha-L-fucosyltransferase, which adds fucose moeities to various proteins. 7876235 24586186 30239796 FUT8 17.523 N-glycan levels (DG1) rs7159888 FUT8 encodes a fucosyltransferase that catalyzes the transfer of fucose to complex glycopeptides. 985526 21203500 30239796 G6PC2 217.046 Fasting glucose-related traits (FPG) rs560887 G6PC2 encodes a pancreas-specific glucose-6-phosphatase. This enzyme influences the fasting glucose set point for basal insulin secretion. 23274894 20081858 30239796 G6PD 8.046 Bilirubin levels rs766420 G6PD encodes the glucose-6-phosphate dehydrogenase, an enzyme critical to red blood cell metabolism. G6PD deficiency results in accumulation of bilirubin, a breakdown product of heme. 11445808 19419973 30239796 GADL1 115.02 N-acetylcarnosine/creatinine rs6800284 GADL1 encodes the glutamate decarboxylase-like protein 1 which produces beta-alanine, a component of the dipeptide carnosine. 23038267 36357675 36357675 GALNT2 40.454 HDL Cholesterol rs4846914 GALNT2 encodes an acetylgalactosaminyltransferase which glycosylates the APOC3 protein, which in turn inhibits the lipoprotein lipase (LPL) enzyme which hydrolyzes triglycerides from triglyceride-containing lipoproteins, leading to the generation of HDL 22152306 GLGC 30239796 GAMT 10.94 guanidinoacetate rs189224273 GAMT encodes guanidinoacetate N-methyltransferase, a methyltransferase that converts guanidoacetate, the metabolite observed at this locus, to creatine. 13192118 36357675 36357675 GATM 212.45 homoarginine/lysine rs1145091 GATM encodes glycine amidinotransferase. This enzyme produces the homoarginine when using lysine as a substrate., GATM encodes glycine amidinotransferase. This enzyme produces the Homoarginine when using lysine as a substrate. 3800397|23010440 36357675 36357675 GBA3 381.93 methyl glucopyranoside (alpha + beta)/myo-inositol rs358231 GBA3 encodes a beta-glucosidase which can hydrolyze and release glucose from a variety of glucosides including methylglucoside, the metabolite observed here. 11389701 36357675 36357675 GC 108.699 Vitamin D insufficiency rs2282679 GC encodes the vitamin D binding protein which transports multiple forms of vitamin D 49052 20541252 30239796 GCDH 219.72 glutarylcarnitine (C5)/creatinine rs8012 GCDH encodes a glutaryl-CoA dehydrogenase which catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA. 3081514 36357675 36357675 GCH1 88.91649738016973 dopamine 3-O-sulfate rs17128050 GCH1 encodes GTP cyclohydrolase 1 which catalyzes the first step in the biosynthesis of tetrahydrobiopterin. Tetrahydrobiopterin is a cofactor for tyrosine hydroxylase (encoded by TH). Tyrosine hydroxylase converts tyrosine to L-DOPA. L-DOPA is then converted to the metabolite observed here, 3-methoxytyrosine, by the enzyme catechol-O-methyltransferase (encoded by COMT). TH and COMT are also associated with 3-methyoxytyrosine. 2463916 35347128 35347128 GCK 98.541 MAGIC Fasting Glucose GWAS/Metabochip 2012 rs6975024 GCK encodes glucokinase which directly phosphorylates glucose and thus contributes to glucose homeostasis 1871135 MAGIC 30239796 GCKR 148.21481257997064 mannose rs1260326 GCKR encodes a glucokinase inhibitor which influences levels of glucose and numerous downstream metabolites. 2917560 35347128 35347128 GCSH 12.523 Glycine rs10083777 GCSH encodes the glycine cleavage system H protein which is involved in the degradation of glycine. GCSH deficiency leads to excess plasma glycine. 18941301 27005778 30239796 GDPD1 10.13 1-(1-enyl-palmitoyl)-2-docosahexaenoyl-GPE (P-16:0/22:6)* rs11453938 GDPD1 encodes a lysophospholipase D enzyme with observed activity against N-palmitoyl-lysoplasmenylethanolamine, that is, a phosphatidylethanolamine with a single fatty acid chain, a palmityoyl moeity at the C-1 position, attached via an alkenyl ether (-O-CH=CH-) link to the glycerol backbone. The observed molecule is also a phosphotidylethanolamine with a palmityoyl moeity at the C-1 position, attached via an alkenyl ether (-O-CH=CH-) link, with an additional fatty acid chain at the C-2 position, attached via the more typical ester link. The observed molecule is thus likely upstream of the known lysophospholipase D substrate. 25596343 36357675 36357675 GGH 15.71063404847997 gamma-glutamylglycine rs200592548 GGH encodes gamma-glutamyl hydrolase, primarily known for its activity on polyglutamyl folate. Dipeptides with a gamma-linked glutamate residue represent a plausible but unstudied set of potential substrates. 18902391 35347128 35347128 GGT1 90.62 cysteine-glutathione disulfide/cys-gly, oxidized rs2006227 GGT1 encodes gamma-glutamyltransferase 1 which catalyzes the transfer of the glutamyl moiety of glutathione to a number of different amino acids and can take the analyte reported here (the cysteine-glutathione mixed disulfide) as a substrate. 6130452 36357675 36357675 GLDC 81.37 3-methylglutarylcarnitine (2) rs1658973 GLDC encodes glycine dehydrogenase which takes glycine as a substrate. GLDC deficiency causes excess of glycine. 4585091 36357675 36357675 GLS2 78.26 threonine/glutamine rs1043011 GLS2 encodes the mitochondrial phosphate-activated glutaminase which catalyzes the hydrolysis of glutamine to glutamate and ammonia. 10620514 36357675 36357675 GLTPD2 69.81559251458768 palmitoyl dihydrosphingomyelin (d18:0/16:0) rs79202680 GLTPD2 encodes a protein homologous to a ceramide-1-phosphate transfer protein, which acts on ceramide-1-phosphate, which is structurally related to the metabolite observed at this locus, palmitoyl dihydrosphingomyelin. 26234207|23863933 35347128 35347128 GLYAT 16.94 N-acetylglycine rs11229675 GLYAT encodes glycine-N-acyltransferase which can create a variety of acylglycine conjugates including the metabolite observed here, N-acetylglycine. 13174534 36357675 36357675 GMPR 17.987584625237567 xanthosine rs6459467 GMPR encodes guanosine monophosphate reducatase which converts guanosine monophosphate to inosine monophosphate which can subsequently be converted to hypoxanthine by the enzyme purine-nucleoside phosphorylase. 218932 35347128 35347128 GMPS 15.344189505504747 xanthosine rs183728597 GMPS encodes guanosine monophosphate (GMP) synthase which takes xanthosine monophosphate (XMP) as a substrate to generate GMP. 240826 35347128 35347128 GNMT 62.699 Plasma homocysteine levels (post-methionine load test) rs9296404 GNMT encodes an enzyme which produces S-adenosylhomocysteine. S-adenosylhomocysteine can be converted to homocysteine by the enzyme S-adenosylhomocysteine hydrolase 10843803 24651765 30239796 GNPTAB 13.003444550366634 aspartate rs1209353188 GNPTAB encodes an N-acetylglucosamine-1-phosphotransferase which produces aspartylglucosamines. The eventual degradation of aspartylglucosamine produces aspartate. 6457829 35347128 35347128 GOT2 303.7 imidazole lactate/creatinine rs11076256 GOT2 encodes the enzyme aspartate aminotransferase which can take each of the aromatic amino acids as substrates. In particular, GOT2 catalyzes the conversion of phenylalanine to phenylpyruvate which is then converted to phenyllactate. 4623131 36357675 36357675 GPCPD1 9.02 glycerol 3-phosphate rs73075609 GPCPD1 encodes a choline-releasing glycerophosphodiesterase which converts glycerol phosphocholine to choline and glycerol 3-phosphate, the metabolite observed here. 22570503 36357675 36357675 GPIHBP1 8.663 HDL Cholesterol rs10087900 GPIHBP1 encodes the glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1, a receptor for the HDL. 12496272 GLGC 30239796 GPT 22.17 aspartate/malate rs10108836 GPT encodes alanine aminotransferase which takes alanine as a substrate and produces glutamate which is one step removed from aspartate. 9119391 36357675 36357675 GSTZ1 17.73754891026957 maleate rs7972 GSTZ1 encodes a maleylacetoacetate isomerase which converts maleylacetoacetate to fumarylacetoacetate. Hydrolysis of maleylacetoacetate produces the metabolite observed here, maleate. 9925947 35347128 35347128 GUSB 8.097 Calcium levels rs17711722 GUSB encodes a glucuronidase which induces the opening of the calcium-specific kidney-specific channel, TRPV5. 18495742 24068962 30239796 HACL1 18.87 2-hydroxydecanoate rs149765139 HACL1 encodes 2-hydroxyacyl-CoA lyase 1 which catalyzes the shortening of long chain 2-hydroxy fatty acids, like the observed metabolite, 2-hydroxydecanoate. 17956236 36357675 36357675 HADHA|HADHB 15.328919767261151 3-hydroxylaurate rs116654420 HADHA|HADHB together encode a mitochondiral heterodimer which is involved in fatty acid beta oxidation. The alpha subunit encodes the 3-hydroxyacyl-CoA dehydrogenase activity. 1550553 35347128 35347128 HAL 75.0565054840939 trans-urocanate rs3819817 HAL encodes histidine ammonia-lyase which converts histidine to the metabolite seen here, trans-urocanic acid 13018112 35347128 35347128 HAO2 85.27 alpha-hydroxyisovalerate rs41313995 HAO2 encodes a 2-hydroxyacid oxidase which catalyzes the oxidation of L-alpha-hydroxy acids; alpha-hydroxyisovalerate or a related metabolite may be a potential substrate 10777549 36357675 36357675 HDAC10 30.648783654660658 N-acetylputrescine rs61748567 HDAC10 encodes a polyamine deacetylase. The metabolites observed at this locus are acetylated polyamines. 28516954 35347128 35347128 HDAC6 79.43842163169904 N6-acetyllysine rs61735967 HDAC6 encodes a lysine deacetylase that can act on multiple proteins. The observed metabolite, acetyllysine, is the substrate. 12606581 35347128 35347128 HFE 96.565 Iron|serum rs1800562 HFE encodes the hereditary hemochromatosis protein which binds transferrin receptor which binds transferrin which binds iron 9465039 25352340 30239796 HIBCH 167.0485167692477 methylmalonate (MMA) rs291459 HIBCH encodes 3-hydroxyisobutyryl-CoA hydrolase which generates free hydroxyisobutyrate in the breakdown of valine. Methylmalonate is derived from hydroxyisobutyrate. 13457352 35347128 35347128 HLCS 7.269 2-Hydroxyisovalerylcarnitine rs1571700 HLCS encodes a biotin apo-protein ligase which attaches biotin to four biotin-dependent enymes, including enzymes involved in branched chain amino acid catabolism. Holocarboxylase synthetase deficiency results in increased levels of 3-Hydroxyisovalerylcarnitine. 19201116 26401656 30239796 HMGCR 77.108 LDL Cholesterol rs12916 HMGCR encodes HMG-CoA reductase, the rate-limiting enzyme for cholesterol biosynthesis 1967820 GLGC 30239796 HNF4A 33.785 HDL Cholesterol rs1800961 HNF4A drives expression of many cholesterol related genes including HMGCR 21071704 GLGC 30239796 HP 40.398 LDL cholesterol rs2000999 HP encodes haptoglobin which binds to ApoA-I, the primary protein component of HDL. 23420675 24097068 30239796 HPD 49.84 beta-hydroxyisovalerate/4-hydroxyphenylpyruvate rs11043222 HPD encodes 4-hydroxyphenylpyruvate dioxygenase. 4-hydroxyphenylpyruvate is the second strongest association signal at this locus. 873932 36357675 36357675 HSD17B10 121.28291227507299 tiglylcarnitine (C5:1-DC) rs201378370 HSD17B10 encodes the 2-methyl-3-hydroxybutyryl-CoA dehydrogenase necessary for isoleucine degradation. Tiglyl-CoA is converted into its substrate and a enzyme deficiency results in accumulation of tiglylcarnitine and tigloylglycine. 7639524|11102558 35347128 35347128 HSD17B2 10.81 dehydroisoandrosterone sulfate (DHEA-S) rs2911282 HSD17B2 encodes a 17-beta-hydroxysteroid dehydrogenase which converts testosterone to androstenedione. This is further metabolized to dehydroepiandrosterone (DHEA) before being sulfated to produce the metabolite observed here, dehydroisoandrosterone sulfate (DHEA-S). 8099587 36357675 36357675 HSD3B7 10.261457259071214 3beta,7alpha-dihydroxy-5-cholestenoate rs7206511 HSD3B7 encodes a 3 beta-hydroxysteroid dehydrogenase specific for C27 bile acids. The observed metabolite is a substrate. 11067870 35347128 35347128 HYKK 158.61 5-hydroxylysine rs1847530 HYKK encodes hydroxylysine kinase which specifically phosphorylates the metabolite observed at this locus, 5-hydroxylysine. Hydroxylysine is a breakdown product of collagen, as is the other metabolite observed at this locus, hydroxyproline. The enzyme, however, only acts on hydroxylysine. 4621658|22241472 36357675 36357675 IDO1 16.45 kynurenine rs10085935 IDO1 and IDO2 encode the two indoleamine 2,3-dioxygenase isozymes. Both enzymes take tryptophan and tryptophan-related metabolites as substrates, but IDO1 is more active [18282734]. IDO1 has known activity against 5-hydroxy-tryptophan [10833386]. Common polymorphisms in IDO2 ablate activity but have no effect on this endpoint [17671174] 10833386 36357675 36357675 IGF2BP2 7.757 MAGIC Fasting Glucose GWAS/Metabochip 2012 rs7651090 IGF2BP2 encodes a protein which binds insulin-like growth factor 2 mRNA. 9891060 MAGIC 30239796 INSIG2 11.77 LDL Cholesterol rs10490626 INSIG2 encodes a protein that plays a key role in regulating the SREBP cleavage-activating protein (SCAP), thus providing a means for feedback regulation of cholesterol synthesis over a wide range of sterol concentrations. 12242332 GLGC 30239796 IRF2BP2 27.153 Total Cholesterol rs558971 IRF2BP2 encodes a protein which binds to the interferon regulatory factor 2 transcription factor. This transcription factor is essential for the activation of the ABCA1 cholesterol transporter. 26195219 GLGC 30239796 ISYNA1 13.95 myo-inositol rs35231179 ISYNA1 encodes an inositol-3-phosphate synthase, which converts d-glucose 6-phosphate to 1-d-myo-inositol 3-phosphate. 15024000 36357675 36357675 IVD 117.47 propionylcarnitine/isovalerylcarnitine rs12594728 IVD encodes isovaleryl-CoA dehydrogenase which acts on isovaleryl-CoA in the third step of leucine catabolism. Isovaleryl-CoA is converted to isovalerylcarnitine for circulation. 3597357 36357675 36357675 KLKB1 47.398 Blood metabolite levels (bradykinin, des-arg(9)) rs4253311 KLKB1 encodes kallikrein, a serine protease which releases bradykinin from kininogen. 8662673 24816252 30239796 KMO 199.71 kynurenate/quinolinate rs61825638 KMO encodes kynurenine 3-monooxygenase which acts on kynurenine. Alternatively kynurenine can be converted into the metabolite seen here, kynurenate. 4389188 36357675 36357675 KNG1 12.222 Blood metabolite levels (bradykinin, des-arg(9)) rs5030062 KNG1 includes the coding sequence for the bradykinin peptide. 2989293 24816252 30239796 KYAT1 44.76 indolelactate rs199627869 KYAT1 encodes a kyneurenine aminotransferase, also known as hKAT-1, which can convert tryptophan to indolepyruvate. Indolepyruvate is then converted to indolelactate. 15606768 36357675 36357675 KYAT3 315.08 imidazole lactate/creatinine rs2893083 KYAT3 encodes an aminotransferase with known activity against kyneurenine and other amino acids. Related enzymes have activity against histidine, generating imidazole pyruvate. This can then be converted to imidazole lactate. 25231977|15606768 36357675 36357675 KYNU 19.34 xanthurenate rs17808482 KYNU encodes kynureninase a vitamin B6 dependent enzyme which hydrolyzes the tryptophan metabolite kynurenine. Xanthurenate is an alternate metabolite of kynurenine. In animals deprived of vitamin B6, excretion of xanthurenate is increased. 13032082 36357675 36357675 L2HGDH 10.595166283380062 2-hydroxyglutarate rs12886516 L2HGDH encodes the mitochondrial L-2-hydroxyglutarate dehydrogenase which generates 2-oxoglutarate from the metabolite observed here, L-2-hydroxyglutarate. 8241290 35347128 35347128 LACTB 93.10651565378151 succinylcarnitine (C4-DC) rs189796619 LACTB is an important mitochondrial protein influencing mitochondrial lipid production. Succinylcarnitine, the observed metabolite at the locus, is a product of the Krebs cycle which occurs within the mitochondrion. 28642719 35347128 35347128 LCAT 53.097 HDL cholesterol rs16942887 LCAT encodes lecithin-cholesterol acyltransferase which travels with HDL, esterifying cholesterol to cholesterol ester for incorporation into the HDL particles for transport back to the liver. 4868699 24097068 30239796 LCT 52.65 1,5-anhydroglucitol (1,5-AG) rs4988235 LCT encodes lactase, a disaccharidase which hydrolyzes lactose, enabling the constituent monosaccharides to be absorbed in the small intestines. 1,5-anhydroglucitol is short-term marker of plasma glucose levels because it competes with monosaccharides for reabsorption in the kidneys. A second associated metabolite, galactonate, is derived from a product of the lactase reaction. 16992869|18088226 36357675 36357675 LDHA 160.8 imidazole lactate/alpha-hydroxyisovalerate rs4150678 LDHA encodes lactate dehydrogenase. In addition to producing pyruvate from lactate, this enzyme can produce the observed metabolite from the keto acid 3-methyl-2-oxobutanoate 26014429 36357675 36357675 LDLR 261.415 LDL Cholesterol rs6511720 LDLR encodes the LDL receptor. 226968 GLGC 30239796 LDLRAP1 16.519 LDL Cholesterol rs10903129 LDLRAP1 encodes an adapter protein which binds to the LDL receptor. Mutations in this gene cause a form of familial hypercholesterolemia. 15166224 GLGC 30239796 LHX3 13.699 Thyroid hormone levels (FT4: free thyroxine) rs7860634 LHX3 encodes pituitary-specific transcription factor which is critical for pituitary gland development. The pituitary gland produces thyroid stimulating hormone which directs the thyroid gland to produce thyroxine (T4). 8638120 23408906 30239796 LIPC 264.58 1-palmitoyl-2-docosahexaenoyl-GPE (16:0/22:6)*/1-palmitoyl-2-docosahexaenoyl-GPC (16:0/22:6) rs1077835 LIPC encodes hepatic triglyceride lipase which hydrolyses triglycerides. The enzyme plays a key role in regulating levels of HDL. 7417375 36357675 36357675 LIPG 65.746 HDL Cholesterol rs4939883 LIPG encodes endothelial lipase which acts on HDL. Inhibition of endothelial lipase causes increased HDL cholesterol levels in vivo 12569161 GLGC 30239796 LPA 16.141 Total Cholesterol rs10455872 LPA encodes the lipoprotein(a) protein, a constituent of the lipoprotein(a) particle, a carrier of cholesterol. 24977982 GLGC 30239796 LPCAT3 48.523 Red blood cell fatty acid levels (OA) rs2110073 LPCAT3 encodes a lysophosphatidylcholine acyltransferase which takes the CoA version of oleic acid to convert lysophosphatidylcholine to phosphatidylcholine. 18781350 25500335 30239796 LPCAT4 9.85 1-eicosenoyl-GPC (20:1)* rs2279686 LPCAT4 encodes a lysophosphatidylcholine acyltransferase which can convert lysophosphatidylcholines, like the metabolite observed here (1-eicosenoyl-GPC), to a phosphatidycholine. 18287005 36357675 36357675 LPGAT1 8.523 Stearic acid (18:0) plasma levels rs11119805 LPGAT1 encodes a lysophosphatidylglycerol acyltransferase which transfers long-chain acyl-CoAs to lysophosphatidylglycerol with a demonstrated preference for stearoyl-CoA. 15485873 23362303 30239796 LPL 198.74 Triglycerides rs12678919 LPL encodes the lipoprotein lipase which hydrolyzes triglycerides. LPL deficiency results in accumulation of triglycerides. 13712364 GLGC 30239796 LRPAP1 11.795 Triglycerides rs6831256 LRPAP1 encodes a protein which binds the LDL-receptor-related protein and the VLDL receptor affecting distribution of lipoprotein particles. 7538675 GLGC 30239796 MBOAT7 367.68 1-stearoyl-2-linoleoyl-GPI (18:0/18:2)/1-stearoyl-2-arachidonoyl-GPI (18:0/20:4) rs34564463 MBOAT7 encodes a lysophosphatidylinositol acyltransferase that has specificity for arachidonoyl-CoA as an acyl donor. Arachidonate is readily converted to arachidonoyl-CoA. Thus the associated ratio is closely linked to the substrate/product pair for this enzyme. 18094042 36357675 36357675 MCCC1 38.14 beta-hydroxyisovalerate rs10937112 MCCC1 encodes methylcrotonoyl-CoA carboxylase 1 which catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA in the breakdown of leucine. An alternate fate of 3-methylcrotonyl-CoA is 3-hydroxyisovaleryl-CoA. 3-Methylcrotonyl-CoA carboxylase deficiency has been associated with elevated urinary 3-hydroxyisovalerylcarnitine levels. 19339287 36357675 36357675 MFSD2A 22.3 1-palmitoyl-GPE (16:0) rs61781290 MFSD2A encodes a lysophosphotidylcholine transporter. The observed metabolites are lysolipids. 24828044 36357675 36357675 MGAM 35.56 1,5-anhydroglucitol (1,5-AG) rs7801101 MGAM encodes maltase-glucoamylase, a disaccharidase which hydrolyzes maltase enabling the constituent monosaccharides to be absorbed in the small intestines. 1,5-anhydroglucitol is short-term marker of plasma glucose levels because it competes with monosaccharides for reabsorption in the kidneys. 18088226 36357675 36357675 MLXIPL 99.866 Triglycerides rs17145738 MLXIPL encodes the carbohydrate-responsive element-binding protein, a transcription factor for multiple lipogenic enzymes. 16890538 28334899 30239796 MMACHC 8.699 Homocysteine levels rs4660306 MMACHC encodes a cobalamin-binding protein. Defects in MMACHC are a known cause of homocystinuria. 16311595 23824729 30239796 MMUT 9.699 Homocysteine levels rs9369898 MUT is a cobalamin-dependent enzyme. Cobalamin is also needed in a reaction taking the homocysteine as a substrate 7901104 23824729 30239796 MOCOS 12.5 7-methylguanine rs59942447 MOCOS encodes molybdenum cofactor sulfurase which sulfurates the molybdenum cofactor used by aldehyde oxidase (encoded by AOX1). Aldehyde oxidase acts on many substrates including purines. Activity against the observed metabolite, 7-methylguanine, has been reported. The AOX1 locus harbors its own associations with this same metabolite. 11302742|5044040 36357675 36357675 MOCS1 9.07 cysteine s-sulfate rs11964984 MOCS1 encodes the molybdenum cofactor biosynthesis protein 1 which is essential for the maturation of sulfite oxidase (encoded by SUOX). Sulfite oxidase converts sulfite to sulfate, a key step in cysteine catabolism. Deficiency of either enzyme leads to accumulation of sulfite which then reacts with cystine to produce cysteine s-sulfate, the metabolite observed here. 16140720 36357675 36357675 MTHFR 103.398 Homocysteine levels rs1801133 MTHFR encodes methylenetetrahydrolate reductase, an enzyme that catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is the methyl donor in the conversion of homocysteine to methionine. Defects in MTHFR lead to homocysteinuria. 5057914 23824729 30239796 MTNR1B 214.971 MAGIC Fasting Glucose GWAS/Metabochip 2012 rs10830963 MTNR1B encodes a melatonin receptor. Melatonin stimulates glucose uptake. 16842543 MAGIC 30239796 MTR 9.699 Homocysteine levels rs2275565 MTR encodes 5-methyltetrahydrofolate-homocysteine methyltransferase. The enzyme acts on homocysteine to produce methionine 2407589 23824729 30239796 MUC1 35.699 Magnesium levels rs4072037 MUC1 encodes a mucin protein which forms a mucosal layer in intestines and kidney and may regulate absorption of magnesium 1983814 20700443 30239796 MVK 19.604 HDL Cholesterol rs2241210 MVK encodes mevalonate kinase which synthesizes a precursor to cholesterol. 2153681 GLGC 30239796 MYLIP 16.68 LDL Cholesterol rs3757354 MYLIP encodes an E3 ubiquitin ligase which ubiquitinates the low density lipoprotein receptor (LDLR), which promotes the degradation of LDLR, influencing the circulating levels of LDL-cholesterol. 19520913 GLGC 30239796 NAAA 11.596707854841746 N-stearoyltaurine rs112197434 NAAA encodes the N-acylethanolamine-hydrolyzing acid amidase. N-acyl taurines such as the observed metabolite here, n-stearoyltaurine, represent a potential substrate class for NAAA 15655246 35347128 35347128 NAALAD2 58.45580788923497 beta-citrylglutamate rs7940029 NAALAD2 encodes a beta-citrylglutamate hydrolase which can act on the metabolite seen here, beta-citrylglutamate. 21908619 35347128 35347128 NADK2 10.453704164878557 lysine rs16902835 NADK2 encodes a mitochondrial NAD kinase, converting NAD to NADP, an essential cofactor for multiple mitochondrial enzymes including aminoadipate-semialdehyde synthase which catalyzes the first two steps in the degradation of lysine. Mutations in NADK2 cause hyperlysinemia. 24847004 35347128 35347128 NAGS 9.52 N-acetylglutamate rs860354 NAGS encodes N-acetylglutamate synthase which synthesizes the metabolite observed at this locus, N-acetylglutamate. 25771 36357675 36357675 NAT16 211.57 N-acetylhistidine rs740104 NAT16 encodes a histidine acetytransferase which generates N-acetylhistidine, the metabolite observed here 24121108 36357675 36357675 NAT2 1112.67 5-acetylamino-6-formylamino-3-methyluracil rs1801280 NAT2 encodes an N-acetyltransferase which can produce the observed metabolite, 5-acetylamino-6-formylamino-3-methyluracil (AFMU), as a downstream product of caffeine. The nearby paralog, NAT1, has not been shown to have this activity. 10744128 36357675 36357675 NAT8 3376.13 N-delta-acetylornithine/N2,N5-diacetylornithine rs13408433 NAT8 shows sequence similarity to N-acetyltransferases. N-acetylcitrulline may be a product or related to a product. 18662894 36357675 36357675 NAXE 7.744 HDL Cholesterol rs12145743 NAXE (formerly APOA1BP) encodes an APOA1 binding protein which promotes cholesterol efflux into high density lipoprotein (HDL) particles. 23719382 GLGC 30239796 NIT2 38.74112337062787 alpha-ketoglutaramate rs3830303 NIT2 encodes an omega-amidase which converts the metabolite observed here, alpha-ketoglutaramate, to alpha ketoglutarate. 19595734 35347128 35347128 NPC1L1 20.716 LDL Cholesterol rs2073547 NPC1L1 encodes a transporter for cholesterol in the intestine. 14976318 GLGC 30239796 NPL 54.74 N-acetylneuraminate rs116448311 NPL encodes N-acetylneuraminate pyruvate lyase which cleaves of N-acetylneuraminate to form pyruvate and N-acetylmannosamin. The observed metabolite is a substrate of this enzyme. 11737202 36357675 36357675 NR1H3 37.481 HDL Cholesterol rs3847502 NR1H3 encodes the LXR-alpha nuclear hormone receptor. This transcription factor upreguates ABCA1, a cholesterol transporter with a direct impact on HDL levels. 11090131 GLGC 30239796 NR5A1 10.419189027339053 pregnenediol sulfate (C21H34O5S) rs4838190 NR5A1 encodes the steroidogenic factor-1, a transcription factor that regulates many genes involved in steroidogenesis, including SULT2A1 which itself has an association with pregn steroid monosulfate, the metabolite associated with this locus. 22427816 35347128 35347128 NT5C 1083.95 orotidine/pseudouridine rs78625720 NT5C encodes a 5', 3'-nucleotidase which dephosphorylates purine and pyrimidine nucleotides. Orotidine is a purine nucleotide formed with the uracil derivative orotate as the base. 2157703 36357675 36357675 NT5C3A 64.02 orotate rs4316067 NT5C3A encodes a pyrimidine 5'-nucleotidase which dephosphorylates of pyrimidine nucleoside monophosphates, including UMP. Orotate, the metabolite observed here, is converted to UMP by UMP synthase. 15968458 36357675 36357675 NT5E 12.155 Metabolic traits (inosine + 1 other trait) rs494562 NT5E encodes the ecto-5'-nucleotidase which can generate inosine 6271180 21886157 30239796 OAT 34.42817475095917 3-amino-2-piperidone rs121965043 OAT encodes ornithine aminotransferase which converts ornithine to glutamate 5-semialdehyde. The metabolite observed here, 3-amino-2-piperidone, also known as cyclo-ornithine, is a closely related metabolite. 4990629 35347128 35347128 OPLAH 194.68 6-oxopiperidine-2-carboxylic acid/5-oxoproline rs3935209 OPLAH encodes 5-oxoprolinase which catalyzes the ATP-dependent hydrolysis of 5-oxoproline to glutamic acid. 5-oxoproline is the second metabolite associated with this locus. The strongest association is for 6-oxopiperidine-2-carboxylic acid which is structurally closely related. 9233839 36357675 36357675 ORMDL3 17.02 lactosyl-N-palmitoyl-sphingosine rs11327630 ORMDL3 encodes a protein which regulates sphingolipid synthesis by interacting with serine palmitoyl transferase. 20182505 36357675 36357675 PAH 40.13 tyrosine/phenylalanine rs5030861 PAH encodes the enzyme phenylalanine hydroxylase which is the rate-limiting step in phenylalanine catabolism. 4150152 36357675 36357675 PAOX 51.74352279375832 N-acetyl-isoputreanine rs2265908 PAOX encodes an N1-acetylspermidine oxidase. The metabolite observed here, acisoga, is a downstream metabolite of N1-acetylspermidine. 12660232|3558558 35347128 35347128 PARP14|PARP15|PARP9 14.15 nicotinamide rs147939290 The PARP genes encode a family of enzymes that cleave NAD, producing ADP-ribose and nicotinamide, the observed metabolite. 28525742 36357675 36357675 PCCA 25.87 carnitine/propionylcarnitine rs61749895 PCCA encodes one half of propionyl-CoA carboxylase which normally acts on propiony-CoA to produce methylmalonyl-CoA but can also act on butyryl-CoA to produce small amounts of ethylmalonyl-CoA. 13752080 36357675 36357675 PCK2 10.28 succinylcarnitine rs79873985 PCK2 encodes the mitochondrial phosphoenolpyruvate carboxykinase which influences krebs cycle metabolites by converting oxaloacetate to phosphoenolpyruvate. The observed metabolite, succinylcarnitine, is derived from succinyl-CoA, a key krebs cycle intermediate. 13938894 36357675 36357675 PCMT1 18.95703092660682 S-adenosylhomocysteine (SAH) rs9505982 PCMT1 encodes a methyltransferase which produces S-adenosylhomocysteine. PCMT1 is important for reversing oxidative damage in neurons and erythrocytes. Pcmt1 knockout mice show reduced levels of S-adenosylhomocysteine 12023972|11279164 35347128 35347128 PCSK1 14.991 MAGIC Fasting Glucose GWAS/Metabochip 2012 rs4869272 PCSK1 encodes a protease which is involved in maturation of insulin 1843283 MAGIC 30239796 PCSK9 142.067 LDL Cholesterol rs11591147 PCSK9 encodes a protein that binds to the LDLR receptor, promoting its degradation and thus influencing circulating LDL cholesterol levels. Rare gain of function mutations result in greatly elevated LDL cholesterol levels. 12730697 GLGC 30239796 PDPR 10.678 Pyruvate rs74249229 PDPR encodes a component of the pyruvate dehydrogenase complex (PDC) which converts pyruvate into acetyl-CoA. 9395502 27005778 30239796 PDX1 14.876 MAGIC Fasting Glucose GWAS/Metabochip 2012 rs11619319 PDX1 encodes a pancreas-specific transcription factor which induces expression of insulin and SLC2A2 (GLUT2) which each influence glucose levels 7901001|8923459 MAGIC 30239796 PDZK1 29 Urate levels rs1471633 PDZK1 encodes a protein that binds to and regulates the activity of URAT1 (encoded by SLC22A12), which is a urate transporter. 15304510 23263486 30239796 PEMT 22.76 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2)*/1-(1-enyl-stearoyl)-2-oleoyl-GPC (P-18:0/18:1) rs897450 PEMT encodes phosphatidylethanolamine N-methyltransferase which methylates phosphatidylethanolamine molecules three times to produce phosphatidylcholine molecules 6497846 36357675 36357675 PHGDH 66.63 serine/asparagine rs561931 PHGDH encodes a phosphoglycerate dehydrogenase which catalyses the first and rate-limiting step in serine biosynthesis. 16589713 36357675 36357675 PLA2G10 141.08 1-dihomo-linolenoyl-GPC (20:3n3 or 6)*/1-dihomo-linoleoyl-GPC (20:2)* rs4985154 PLA2G10 encodes a phospholipase that converts phosphatidylethanolamines and phosphatidylcholines to the corresponding lysolipid 9188469 36357675 36357675 PLTP 54.585 S.HDL.P rs6073958 PLTP encodes phospholipid transfer protein which acts directly on HDL particles. 8664337 27005778 30239796 PM20D2 23.012110390002256 N-acetylcarnosine rs7775554 PM20D2 encodes a dipeptidase that eliminates non-carnosine products of carnosine synthase, this favoring the production of carnosine. 24891507 35347128 35347128 PNLIPRP2 34.92 1-palmitoyl-2-linoleoyl-GPC (16:0/18:2)/1-stearoyl-2-oleoyl-GPC (18:0/18:1) rs4751995 PNLIPRP2 encodes the pancreatic lipase related protein 2 (PLRP2) which hydrolyzes many lipids including phosphotidylcholines which are similar to the metabolite observed here, 1-stearoyl-2-oleoyl-GPC. 17401110 36357675 36357675 PNP 17.980053318321158 N2-methylguanosine rs1760930 PNP encodes purine nucleoside phosphatase which uses phosphate to separate a purine base from its sugar. The metabolite observed here, N2-methylguanosine, is a potential substrate and is closely related to known substrates. 20285042 35347128 35347128 PNPLA7 18.41 1-(1-enyl-palmitoyl)-2-oleoyl-GPC (P-16:0/18:1)*/1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2)* rs4962237 PNPLA7 encodes a lysophosphatidylcholine hydrolase that can act on 1,2-dioleoyl glycerophosphocholine ((C18:1/C18:1 GPC), a molecule similar to the metabolite observed here. 28887301 36357675 36357675 PPARA 8.006 Total Cholesterol rs4253772 PPARA encodes a transcription factor which regulates expression of HDL apolipoproteins 9808609 GLGC 30239796 PPARG 16.075 Total Cholesterol rs7616006 PPARG encodes a transcription factor that upreguates ABCA1 among other proteins involved in lipid metabolism. 11135616 GLGC 30239796 PPM1K 42.28 2-aminobutyrate/3-methyl-2-oxobutyrate rs10018448 PPM1K encodes a phosphatase called PP2Cm for the branched-chain keto acid dehydrogenase (BCKD) complex. BCKD catalyzes an essential step in the catabolism of valine and the other branched chain amino acids. 19411760 36357675 36357675 PRODH 168.2 phenylalanine/proline rs117935223 PRODH encodes proline dehydrogenase which catalyzes the first step in proline degradation 16874462 36357675 36357675 PRODH2 10.2 trans-4-hydroxyproline rs3761097 PRODH2 encodes hydroxyproline dehydrogenase which converts the metabolite observed at this locus, trans-4-hydroxyproline, to L-1-pyrroline-3-hydroxy-5-carboxylate. 25697095 36357675 36357675 PSPH 37.2 serine/asparagine rs4470984 PSPH encodes phosphoserine phosphatase which produces serine 16589713 36357675 36357675 PTRH1 109.84 N-acetylalanine/N-formylmethionine rs550045 PTRH1 encodes a mitochondrial-directed peptidyl-tRNA hydrolase which releases tRNA from peptidyl-tRNA chains. The observed metabolite, N-formylmethionine, is likely a consequence of the activity of this enzyme on mitochondrial proteins which are initiated with formyl-methionine. 4981785 36357675 36357675 PYCR3 70.37955161528829 S-1-pyrroline-5-carboxylate rs2242090 PYCR3 encodes a pyrroline-5-carboxylate reductase which generates proline from the observed metabolite. 23024808 35347128 35347128 PYROXD2 2181.1045774539607 N6-methyllysine rs2147896 One of the strongest and most reproducible signals in metabolite GWAS involves this locus and mono- or dimethyl derivatives of small molecules. The exact function of PYROXD2 remains a mystery. 24586186 35347128 35347128 QPCT 30.04803141550709 pyroglutamylglutamine rs77684493 QPCT encodes a glutaminyl-peptide cyclotransferase which cyclizes an N-terminal glutamine residue. The metabolite observed here, pyroglutamylglutamine, is a likely product of this reaction. 3473473 35347128 35347128 RBP4 23.54 retinol (Vitamin A) rs10882283 RBP4 encodes a retinol-binding protein that transports retinol in the blood. 2444024 36357675 36357675 SARDH 50.78 sarcosine (N-Methylglycine) rs111389997 SARDH encodes sarcosine dehydrogenase converts sarcosine to glycine and formaldehyde. 13716069 36357675 36357675 SAT2 135.35 N6-acetyllysine rs13894 SAT2 encodes an acetyltransferase which can act on thialysine and lysine. Acetylation of lysine results in N6-acetyllysine, the metabolite observed at this locus. 15283699 36357675 36357675 SCARB1 32.135 HDL Cholesterol rs838876 SCARB1 encodes a scavanger receptor which can act as an HDL receptor. 8560269 GLGC 30239796 SCD 120.22 1-(1-enyl-palmitoyl)-2-palmitoleoyl-GPC (P-16:0/16:1)*/1-(1-enyl-stearoyl)-2-oleoyl-GPC (P-18:0/18:1) rs603424 SCD encodes a stearyl-CoA desaturase which acts on medium chain-length acyl-CoAs to bring about the delta 9 desaturation of various fatty acids, such as the conversion of myristate (14:0) to myristoleate (14:1n5). 8453 36357675 36357675 SCD5 44.361410916707285 lignoceroylcarnitine (C24) rs141560958 SCD5 encodes stearoyl-CoA desaturase which catalyzes the formation of monounsaturated fatty acids from saturated fatty acids. The metabolite observed here, the acylcarnitine of a long chain saturated fatty acid, is a potential substrate. 15907797 35347128 35347128 SEC14L2 32.1322968667299 gamma-tocopherol/beta-tocopherol rs182488695 SEC14L2 encodes a tocopherol-binding protein 10829015 35347128 35347128 SELENBP1 19.523 Blood trace element (Cu levels) rs2769264 SELENBP1 encodes a selenium-binding protein. The Arabidopsis ortholog (61% identity) has been shown to bind copper. 25274629 23720494 30239796 SERPINA6 16.520568662802262 cortisol rs6575415 SERPINA6 encodes a serpin family member which specifically binds and transports corticosteroids including the metabolite observed here, cortisol. 3299377 35347128 35347128 SERPINA7 105.50737927795682 thyroxine rs1804495 SERPINA7 encodes the thyroxine-binding globulin protein. 3094014 35347128 35347128 SGPP1 472.35 palmitoyl dihydrosphingomyelin (d18:0/16:0)*/sphingomyelin (d18:1/14:0, d16:1/16:0)* rs35372182 SGPP1 encodes a sphingosine-1-phosphate phosphatase which dephosphorylates sphingosine-1-phosphate to sphingosine which can then be incorporated into sphingomyelin. 10859351 36357675 36357675 SHBG 41 Testosterone levels (Testosterone) rs12150660 SHBG encodes the sex-hormone binding globulin which binds which binds to and transports testosterone. 7626508 21998597 30239796 SI 15.27 1,5-anhydroglucitol (1,5-AG) rs34431609 SI encodes sucrase-isomaltase, a disaccharidase which hydrolyzes sucrose enabling the constituent monosaccharides to be absorbed in the small intestines. 1,5-anhydroglucitol is short-term marker of plasma glucose levels because it competes with monosaccharides for reabsorption in the kidneys. 18088226 36357675 36357675 SLC10A2 60.94 glycochenodeoxycholate glucuronide (1)/glycodeoxycholate sulfate rs55971546 SLC10A2 encodes a bile acid transporter. 7860756 36357675 36357675 SLC13A1 98.81022904365312 sulfate rs138989506 SLC13A1 encodes a kidney-specific sodium/sulfate co-transporter. 7690140 35347128 35347128 SLC13A3 18.33 N-acetylaspartate (NAA) rs439143 SLC13A3 encodes a kidney-selective dicarboxylate transporter which can take malate and glutarate (two of the metabolites observed at this locus) as substrates, as well as succinate, citrate and other Krebs cycle derived metabolites. 15561973 36357675 36357675 SLC13A5 17.319 Citrate rs172642 SLC13A5 encodes NaCT, a sodium-coupled citrate transporter. 16973915 27005778 30239796 SLC14A2 17.155 Renal function-related traits (BUN) rs7227483 SLC14A2 encodes a urea transporter expressed in kidney. 11502588 22797727 30239796 SLC16A10 36.15 tyrosine/phenylalanine rs9647629 SLC16A10 encodes the T-type amino acid transporter 1 (TAT1); this transporter transports tryptophan, tyrosine and phenylalanine 11827462 36357675 36357675 SLC16A12 13.96 N-acetylarginine rs7081788 SLC16A12 encodes solute carrier which can take creatine as a substrate. N-acetylarginine is a closely related metabolite. 23578822 36357675 36357675 SLC16A3 52.9 tyrosine/3-(4-hydroxyphenyl)lactate rs35121878 SLC16A3 encodes a monocarboxylate transporter known to act on lactate and pyruvate. The observed metabolite could be a substrate or could be metabolically linked to a substrate., SLC16A3 encodes a monocarboxylate transporter known to act on lactate and pyruvate. Malate and pyruvate are linked by the activity of malate dehydrogenase. 9425115 36357675 36357675 SLC16A9 234.06 carnitine rs1171614 SLC16A9 encodes a carnitine efflux transporter. 21886157 36357675 36357675 SLC1A4 55.16 2-aminobutyrate rs72538440 SLC1A4 encodes a neutral amino acid transporter with demonstrated activity for alanine, serine, cysteine and threonine. 2-aminobutyrate is structurally similar to these amino acids. 7896285 36357675 36357675 SLC22A1 212.28 isobutyrylcarnitine rs662138 SLC22A1 encodes OCT1, an organic cation transporter with activity towards acylcarnitine. 28942964 36357675 36357675 SLC22A10|SLC22A24|SLC22A25|SLC22A9 379.41 etiocholanolone glucuronide rs182462158 SLC22A24/SLC22A25/SLC22A10/SLC22A9 encode a family of solute carriers expressed in liver and kidney. SLC22A9 is the best characterized of these and is known to transport sulfated steroids similar to some of the metabolites observed at this locus. 17393504 36357675 36357675 SLC22A11 22.08 4-androsten-3beta,17beta-diol monosulfate (2) rs35008345 SLC22A11 encodes solute carrier family which can transport steroid sulfate metabolites similar to the metabolite observed here, 4-androsten-3beta,17beta-diol monosulfate. 18501590 36357675 36357675 SLC22A12 62.523 Renal function-related traits (urea) rs504915 SLC22A12 encodes the URAT1 transporter, a kidney urate reuptake transporter. The nearby gene SLC22A11 encodes the hOAT4 transporter which primarily transports steroid molecules and has only very weak affinity for urea. 12024214|27105641 22797727 30239796 SLC22A16 171.85 sphingosine 1-phosphate/linoleoylcarnitine* rs72939920 SLC22A16 encodes transporter specific for carnitine 12089149 36357675 36357675 SLC22A4|SLC22A5 74.79 valine/isovalerylcarnitine rs538021413 SLC22A5 encodes the OCTN2 protein, which is the primary transporter reponsible for carnitine homeostasis., SLC22A4 encodes an ergothioneine transporter 20648231, 15795384 36357675 36357675 SLC23A1 21.35 glycerate rs33972313 SLC23A1 encodes an ascorbate-specific transporter principally expressed in the small intestines and kidney. Oxolate and threonate, two of the metabolites observed here, can be derived from ascorbate. 10471399 36357675 36357675 SLC23A2 11.454692883534175 ascorbic acid 3-sulfate rs141583725 SLC23A2 encodes one of two ascorbic acid (vitamin C) transporters. The observed metabolite is a sulfate derivative of ascorbic acid. 10556521 35347128 35347128 SLC23A3 84.09463593123311 glycerate rs192756070 SLC23A3 encodes a transporter from the SLC23 ascorbic acid transporter family but with no detectable ascorbic acid transport activity. Highly expressed in the kidney, likely as a reuptake transporter. Glycerate is a possible substrate. 23506882 35347128 35347128 SLC25A1 21.886 Citrate rs2040771 SLC25A1 encodes the mitochondrial-localized tricarboxylate transporter of citrate. 2804096 27005778 30239796 SLC25A19 12.5 isobutyrylcarnitine rs7222784 SLC25A19 encodes transporter which transports thiamine pyrophosphate into mitochondria. Thiamine is a cofactor for the branched chain dehydrogenase complex which converts keto-valine to isobutyryl-CoA which is then converted to isobutyrylcarnitine, the metabolite observed at this locus. 17035501|4100151 36357675 36357675 SLC25A26 20.646468440922238 2,3-dihydroxy-5-methylthio-4-pentenoate (DMTPA) rs13874 SLC25A26 encodes a transporter which transports S-adenosylmethionine (SAM) into the mitochondria. The metabolite observed here, 2,3-dihydroxy-5-methylthio-4-pentenoate, is derived from SAM. 14674884|29578721 35347128 35347128 SLC25A29 14.02 homoarginine rs3783341 SLC25A29 encodes a transporter which transports homoarginine into mitochondria. 24652292 36357675 36357675 SLC25A45 79.72908836058951 N6,N6,N6-trimethyllysine rs34400381 SLC25A45 encodes an orphan mitochondrial transporter closely related to lysine and carnitine transporters. The metabolite observed here, trimethyllysine, is derived from lysine and produces carnitine and is a possible substrate. 24652292|23266187 35347128 35347128 SLC27A2 13.398 Blood metabolite ratios (10-undecenoate (11:1n1)/X-11438) rs1365505 SLC27A2 encodes a very-long-chain acyl-CoA synthetase which activates fatty acids by forming their coenzyme A derivatives. 10198260 24816252 30239796 SLC27A5 12.362810577851238 3b-hydroxy-5-cholenoic acid rs147464959 SLC27A5 encodes a bile acid-CoA ligase which transfers CoA to various bile acids including cholic acid which is derived from 7-alpha-hydroxy-3-oxo-4-cholestenoate, the metabolite observed at this locus. 17401 35347128 35347128 SLC28A1 30.819587367161677 5,6-dihydrouridine rs55990066 SLC28A1 encodes a pyrimidine-specific sodium-nucleoside cotransporter (hCNT1) which can transport uridine. Dihydrouridine, the metabolite observed here, is a frequent modification of this base. 9124315 35347128 35347128 SLC2A2 17.068 MAGIC Fasting Glucose GWAS/Metabochip 2012 rs1280 SLC2A2 encodes a glucose transporter (GLUT2) 2479026 MAGIC 30239796 SLC2A9 700 Urate levels rs12498742 SLC2A9 encodes a urate transporter. 18327257 23263486 30239796 SLC30A10 13.658 Manganese|plasma rs1776029 SLC30A10 encodes a transporter with specificity for manganese. 25319704 26025379 30239796 SLC34A1 12.415668775632469 sulfate rs34225933 SLC34A1 encodes a renal-specific phosphate transporter. Rare mutations in SLC34A1 can lead to renal failure which could explain the impact on creatinine levels. 20335586 35347128 35347128 SLC36A1|SLC36A2 28.14 pyroglutamine* rs77010315 SLC36A1 and SLC36A2 encode paralogous small amino acid transporters (PAT1 and PAT2) which can transport glycine, alanine, proline and hydroxyproline. The observed metabolite, pyroglutamine, is structurally similar to proline and hydroxyproline and may itself be a substrate. The nearby paralog SLC36A3 is expressed exclusively in testes. 12809675 36357675 36357675 SLC36A2 14.68 glycine/citrate|urine rs3846710 SLC36A2 encodes the a proton-coupled amino acid transporter, which is specific for glycine and proline. 19033659 26352407 30239796 SLC38A1 11.97 glutamine rs78855118 SLC38A1 encodes an amino acid transporter (ATA1) with a preference for glutamine. 10891391 36357675 36357675 SLC38A3 13.5 imidazole lactate rs116570617 SLC38A3 encodes a sodium-coupled neutral amino acid (system N/A) transporter (SNAT8) with preference for histidine, alanine, glutamine and arginine. The metabolite oberved here, imidazole lactate, is a metabolite of histidine. 25451601 36357675 36357675 SLC38A4 12.215 Alanine rs4554975 SLC38A4 encodes a liver-enriched amino acid transporter (ATA3) with affinity for most cationic and neutral amino acids including alanine. 11342143|11118514 27005778 30239796 SLC47A1 11.33 N-acetylarginine rs111653425 SLC47A1 encodes the multidrug and toxin extrusion protein 1 (MATE1) which can transport both arginine and asymmetric dimethylarginine, both of which are structurally and metabolically related to the observed metabolite, N-acetylarginine. 23864433 36357675 36357675 SLC51A 42.97 andro steroid monosulfate (1)* rs5855544 SLC51A encodes the alpha subunit of the organic solute transporter (OSTalpha), an intestinal steroid and bile acid transporter which can transport dehydroepiandrosterone sulfate, a metabolite closely related to the observed metabolite, androsterone sulfate. 16317684 36357675 36357675 SLC52A1 24.631341287607775 acisoga rs34556430 SLC52A1 encodes an intestine-specific riboflavin transporter, required for the production of FAD, a cofactor for polyamine oxidase which acts on multiple polyamine. Variants near the PAOX gene are also associated with polyamine levels. 18632736|12660232|3558558 35347128 35347128 SLC5A10 187.15 1,5-anhydroglucitol (1,5-AG) rs61741107 SLC5A10 encodes a kidney-specific mannose transporter, SGLT5. 1,5-anhydroglucitol is short-term marker of plasma glucose levels because it competes with monosaccharides for reabsorption in the kidneys. 24573086 36357675 36357675 SLC5A11 65.034 myo-inositol|urine rs17702912 SLC5A11 encodes a sodium/myo-inositol transporter (SMIT2) which can also transport scyllo-inostiol. 21887366 26352407 30239796 SLC5A6 17.09 pantothenate rs34303460 SLC5A6 encodes a solute transporter with demonstrated activity for pantothenate. 9516450 36357675 36357675 SLC6A12 42.45 betaine rs34265203 SLC6A12 encodes a betaine transporter. 8198549 36357675 36357675 SLC6A13 219.08 creatinine/deoxycarnitine rs10774021 SLC6A13 encodes deoxycarnitine (also known as gamma-butyrobetaine) transporter. 19679820 36357675 36357675 SLC6A19 261.126 tyrosine|urine rs11750211 SLC6A19 encodes a neutral amino acid transporter which can act on tyrosine. The nearby paralog, SLC6A18, is specific for glycine. 15044460|15804236 26352407 30239796 SLC6A20 87.88 pyroglutamine* rs17279437 SLC6A20 encodes a transporter for N-methylglycine, proline and other specific amino acids. 15632147 36357675 36357675 SLC7A11 26.06 hypotaurine rs143229933 SLC7A11 encodes a cystine/glutamate transporter which exchanges cystine for glutamate. Hypotaurine is a sulfur-containing metabolite derived from cysteine, as is cystine, the endogenous ligand for this transporter. 10206947 36357675 36357675 SLC7A2 23.99 glutamine/lysine rs1858715 SLC7A2 encodes an arginine/lysine/ornithine solute carrier enriched in liver. 9174363 36357675 36357675 SLC7A5 80.66 kynurenine/N-acetylalanine rs34380332 SLC7A5 encodes LAT1 which mediates tryptophan/kynurenine exchange. 17896864 36357675 36357675 SLC7A6 58.97 glutarylcarnitine (C5) rs56266914 SLC7A6 encodes a dibasic amino acid transporter which can specifically exchange arginine for lysine. Glutaryl-CoA is a degradation product of lysine, which is then converted to glutarylcarnitine for circulation. 10903140 36357675 36357675 SLC7A7 11.77 methionine sulfone rs11568438 SLC7A7 encodes the y+LAT-1 dibasic amino acid transporter with demonstrated activity toward homoarginine, the metabolite with the second strongest association at this position. 1134847 36357675 36357675 SLC7A9 40.03 homocitrulline rs7247977 SLC7A9 encodes the b(0,+)-type amino acid transporter which transports cystine, arginine, lysine and ornithine. Homocitrulline is derived from lysine., SLC7A9 encodes the b(0,+)-type amino acid transporter which transports cystine, arginine, lysine and ornithine. Methionine can be derived from cysteine as is cystine. 10588648 36357675 36357675 SLCO1A2|SLCO1B1|SLCO1B3 742.62 thyroxine/glycochenodeoxycholate glucuronide (1) rs4149056 SLCO1A2/SLCO1B1/SLCO1B3 encode a family of bile acid and bilirubin transporters. 36357675 36357675 SOAT1 19.57 pregn steroid monosulfate* rs2492778 SOAT1 encodes sterol O-acyltransferase 1 which can acylate pregnenolone in the presence of cholesterol. 22474282 36357675 36357675 SORD 69.047885915093 ribitol rs55901542 SORD encodes sorbitol dehydrogenase which oxidizes multiple polyols including the metabolite observed here, ribitol. 3365415 35347128 35347128 SORT1 271.788 LDL Cholesterol rs646776 SORT1 encodes sortilin, a receptor with a role in VLDL secretion from the liver 20686566 GLGC 30239796 SPHK2 13.304168227173308 sphingomyelin (d18:1/20:1, d18:2/20:0) rs61751862 SPHK2 encodes a sphingosine kinase which produces sphingosine-1-P which can be incorporated into the observed metabolites. S1P also represents the initial step in sphingomyelin catabolism. 10802064 35347128 35347128 SPTLC3 71.29791427856418 sphingomyelin (d18:1/25:0, d19:0/24:1, d20:1/23:0, d19:1/24:0) rs4814175 SPTLC3 encodes a subunit of serine palmitoyltransferase, which catalyzes the first step in de novo sphingolipid biosynthesis. 17023427 35347128 35347128 SRD5A2 44.47 etiocholanolone glucuronide rs112881196 SRD5A2 encodes the type II steroid 5 alpha-reductase enzyme best known for converting testosterone to dihydrotestosterone. The metabolites represented by the ratio detected here are also steroid molecules differing in reduction at carbon 5. The enzyme has known activity against corticosterone. 7734398 36357675 36357675 ST3GAL5 10.440332721611941 lactosyl-N-behenoyl-sphingosine (d18:1/22:0) rs7603766 ST3GAL5 encodes lactosylceramide alpha-2,3-sialyltransferase which transfers a sialic acid moeity to the observed metabolite, lactosyl-n-behenoyl-sphingosine, to produce the ganglioside GM3. 1999428 35347128 35347128 ST6GALNAC1|ST6GALNAC2 13.12 N-acetylneuraminate rs2109101 ST6GALNAC1/ST6GALNAC2 encode a pair of alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferases which transfer N-acetylneuraminate, the metabolite observed here, onto glycan chains on proteins. 9184827 36357675 36357675 STARD3 19.264 HDL Cholesterol rs113612868 STARD3 encodes the StAR-related lipid transfer protein 3 which promotes export of cholesterol to HDL 25014273 GLGC 30239796 STS 43.22709180502873 androstenediol (3beta,17beta) monosulfate (2) rs10458 STS encodes a steroid sulfatase; substrates are sulfated steroids 9252398 35347128 35347128 SUCLA2 7.343 4-methyl-2-oxopentanoate - M22116 rs4941615 SUCLA2 encodes a subunit of succinyl-CoA synthetase a key enzyme in the Krebs cycle. SUCLA2 deficiency results in elevated urinary excretion of leucine degradation products downstream of the analyte detected here (specifically 3-hydroxyisovaleric acid and 3-methylglutaconic acid). 19666145 Twins UK/Kora 30239796 SUCLG2 36.71 succinylcarnitine rs17806888 SUCLG2 encodes the beta subunit of succinate-CoA ligase which acts on succinate-CoA. Acyl-CoAs and acyl-carnitines are readily interconverted. 18392745 36357675 36357675 SULT1A1|SULT1A2|SULT1A3|SULT1A4 52.21731243176503 ascorbic acid 2-sulfate rs10445105 SULT1A1|SULT1A2|SULT1A3|SULT1A4 encode a set of sulfotransferase enzymes that can create sulfated derivates of a variety of metabolites. 10441143|8093002 35347128 35347128 SULT2A1 426.31 pregnen-diol disulfate* rs62129966 SULT2A1 encodes a bile salt sulfotransferase which can catalyze the sulfation of steroids and bile acids. 8575776 36357675 36357675 TAT 23.74 tyrosine/phenylalanine rs201119394 TAT encodes tyrosine aminotransferase which converts tyrosine to 4-hydroxyphenylpyruvate. Enzyme deficiency in this enzyme causes tyrosine accumulation. 1973834 36357675 36357675 TDO2 18.5 tryptophan rs77969526 TDO2 encodes tryptophan 2,3-dioxygenase which acts on tryptophan. 8666386 36357675 36357675 TF 19.177 Iron|serum rs8177240 TF encodes transferrin, a key transporter for iron. 1809186 25352340 30239796 TFR2 18 Iron status biomarkers (iron levels) rs7385804 TFR2 encodes a receptor for transferrin which binds iron 10409623 25352340 30239796 TH 48.90413354652146 dopamine 3-O-sulfate rs200180914 TH encodes tyrosine hydroxylase which converts tyrosine to L-DOPA which can then be converted to the metabolite observed here, dopamine 3-o-sulfate. 14216443 35347128 35347128 THEM4|THEM5 165.59533729912627 cis-4-decenoate (10:1n6) rs6675930 THEM4 and THEM5 encode medium-chain length acyl-CoA thioesterases which release free fatty acids from acyl-CoAs. The observed metabolite is a possible product. 19453107|22586271 35347128 35347128 TKT 37.123608938180816 erythronate rs4687718 TKT encodes transkelolase, an enzyme with a prefererence for D-erythrose 4-phosphate as a substrate. 9924800 35347128 35347128 TM6SF2 19.16915480769139 oleoyl-arachidonoyl-glycerol (18:1/20:4) [1] rs187429064 TM6SF2 encodes a transmembrane 6 superfamily member involved in regulation of hepatic triglyceride synthesis and export. 24927523 35347128 35347128 TMEM86B 33.99 1-palmityl-2-arachidonoyl-GPC (O-16:0/20:4)*/1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4)* rs4606850 TMEM86B encodes a lysoplasmalogenase which hydrolyzes lysoplasmalogens which are derived from plasmalogens such as the metabolite observed here. 21515882 36357675 36357675 TMLHE 93.41094446894766 N6,N6,N6-trimethyllysine rs547447 TMLHE encodes an epsilon trimethyllysine hydroxylase which adds a hydroxyl group to epsilon-n-trimethyl-lysine in the first step of carnitine biosynthesis. 6772170 35347128 35347128 TMPRSS6 139 Iron status biomarkers (iron levels) rs855791 TMPRSS6 encodes a protease which regulates levels of hepcidin which regulates iron levels 25588876 25352340 30239796 TREH 29.523 Serum metabolite levels (Trehalose) rs507080 TREH encodes trehalase which hydrolyses the disaccharide trehalose. 9427547 24625756 30239796 TRIB1 112.652 Triglycerides rs2954022 TRIB1 regulates hepatic lipogenesis. 26517927 GLGC 30239796 TRPM6 14.097 Magnesium levels rs11144134 TRPM6 encodes a cation transporter with demonstrated activity toward magnesium. 14576148 20700443 30239796 TRPM8 10.097 Calcium levels rs1550532 TRPM8 encodes a calcium-permeable channel activated by menthol and cold. 11882888 24068962 30239796 TSPYL5 7.523 Estradiol plasma levels (breast cancer) rs1864729 TSPYL5 induces CYP19A1 expression, which in turn encodes a key enzyme involved in the biosynthesis of estradiol. 23518928 23518928 30239796 TTPA 16.02 gamma-tocopherol/beta-tocopherol rs62508088 TTPA encodes alpha tocopherol transfer protein which specifically binds the alpha-tocopherol form of vitamin E. The metabolite observed at this locus is the closely related gamma- or beta-tocopherol. 7887897 36357675 36357675 TTR 13.65 retinol (Vitamin A) rs1667237 TTR encodes a thyroid hormone-binding protein which transports thryroxine and retinol. 4607556 36357675 36357675 TYMP 249.56 5-methyluridine (ribothymidine) rs131805 TYMP encodes thymidine phosphorylase, which catalyzes the phosphorolysis of thymidine and deoxyuridine. These pyrimidines are metabolically linked to uridine. 7284378 36357675 36357675 UGT1A1|UGT1A10|UGT1A3|UGT1A4|UGT1A5|UGT1A6|UGT1A7|UGT1A8|UGT1A9 923.35 dimethylarginine (SDMA + ADMA)/bilirubin (Z,Z) rs1976391 the UGT genes have UDP-glucuronosyltransferase activity, glucoronidating a variety of substrates. There are 10 paralogs at this locus which likely have different preferences for the different metabolites associated here. 25760529 36357675 36357675 UGT2B10 154.699 Cotinine glucuronidation rs34100980 UGT2B10 encodes a UDP glucuronosyltransferase which glucuronidates cotinine to produce cotinine glucuronide 17576790 25293881 30239796 UGT2B15|UGT2B17 665.0798766737092 deoxycholic acid glucuronide rs13121671 UGT2B15|UGT2B17 encode a pair of diphosphoglucuronosyltransferase that can act on steroids 8399210|8798464 35347128 35347128 UGT3A1 115.3579313726585 5alpha-pregnan-3beta,20beta-diol monosulfate (1) rs6873506 UGT3A1 encodes a UDP glycosyltransferase. This enzyme has demonstrated activity against the bile acid ursodeoxycholic acid. The metabolite detected here is structurally related to the bile acids. 18981171 35347128 35347128 UMPS 220.06 orotate rs2242247 UMPS encodes uridine monophosphate synthetase, the enzyme which converts orotic acid to uridine. Enzyme deficiency results in accumulation of orotic acid. 6893554 36357675 36357675 UPB1 44.33 3-ureidopropionate rs143493067 UPB1 encodes a beta-ureidopropionase which takes the observed metabolite, 3-ureidopropanoate, and produces beta-alanine in the last step of pyrimidine degradation. 13538975 36357675 36357675 UPP1 33.16 5-methyluridine (ribothymidine) rs7794100 UPP1 encodes uridine phosphorylase which catalyzes the interconversion of uridine and uracil. 7488099 36357675 36357675 VLDLR 9.176 Total Cholesterol rs3780181 VLDLR encodes the very low density lipoprotein receptor 8294473 GLGC 30239796 XPNPEP2 77.76853040956932 prolylproline rs4830164 XPNPEP2 encodes a protease which specifically cleaves at a proline residue. Prolylproline is a plausable substrate or product 15361070 35347128 35347128 XYLB 13.53 glycolate|urine rs3132440 XYLB encodes a xylulokinase homolog which phosphorylates D-xylulose, a precursor of glycolate 9783918 26352407 30239796