Table 3.

Metabolite single-nucleotide polymorphisms explaining >15% of the variation in blood

Metabolite	Super pathway	Subpathway	Variance explained	rsID	Consequence	Closest gene	Effect allele	Other allele	EAF	p
N6-methyllysine	Amino acid	Lysine metabolism	0.50	rs2147896	Missense	PYROXD2	A	G	0.64	2.68×10−146
N6,N6-dimethyllysine	Amino acid	Lysine metabolism	0.48	rs2147896	Missense	PYROXD2	A	G	0.64	1.98×10−135
X - 12112	Unannotated	Unannotated	0.44	rs7905265	Downstream gene	PYROXD2	C	G	0.64	6.00×10−119
N2-acetyl,N6,N6-dimethyllysine	Amino acid	Lysine metabolism	0.38	rs10182082	Intron	NAT8	G	C	0.22	6.07×10−38
			0.15	rs7905265	Downstream gene	PYROXD2	C	G	0.64	1.86×10−97
N2-acetyl,N6-methyllysine	Amino acid	Lysine metabolism	0.34	rs7905265	Downstream gene	PYROXD2	C	G	0.64	5.04×10−88
			0.25	rs10182082	Intron	NAT8	G	C	0.22	6.51×10−65
Ethylmalonate	Amino acid	Leucine, isoleucine and valine metabolism	0.30	rs1799958	Missense	ACADS	A	G	0.25	5.87×10−79
			0.01	rs6490297	Intergenic	CABP1	C	T	0.27	9.09×10−28
N-acetylarginine	Amino acid	Urea cycle; arginine and proline metabolism	0.27	rs10168931	Intron	NAT8	A	G	0.23	5.63×10−70
N-delta-acetylornithine	Amino acid	Urea cycle; arginine and proline metabolism	0.26	rs10168931	Intron	NAT8	G	A	0.77	2.02×10−64
N-acetyl-l-methylhistidine*	Amino acid	Histidine metabolism	0.25	rs10206899	Intron	NAT8	C	T	0.23	1.76×10−66
Butyrylcarnitine (C4)	Lipid	Fatty acid metabolism (also BCAA metabolism)	0.23	rs1799958	Missense	ACADS	A	G	0.25	1.75×10−59
N-acetylglutamine	Lipid	Primary bile acid metabolism	0.22	rs4149056	Missense	SLCO1B1	G	T	0.16	4.51×10−39
N-methylpipecolate	Xenobiotics	Bacterial/Fungal	0.21	rs2147896	Missense	PYROXD2	A	G	0.64	6.75×10−54
Deoxycholic acid glucuronide	Lipid	Secondary bile acid metabolism	0.19	rs34594059	Intron	TMPRSS11E	C	C	0.36	5.79×10−45
X - 19141	Unannotated	Unannotated	0.17	rs34436963	3′ UTR	TMPRSS11E	G	A	0.64	2.12×10−43
			0.06	rs1165196	Missense	SLC17A1	G	A	0.45	3.08×10−17
1-Palmitoyl-GPI* (16:0)	Lipid	Lysophospholipid	0.16	rs102275	Intron	TMEM258	T	C	0.64	2.38×10−41
5alpha-androstan-3alpha,17alpha-diol monosulfate	Lipid	Androgenic steroid	0.16	rs1495741	Intergenic	NAT2	G	A	0.23	4.41×10 −41
			0.01	rs1041983	Synonymous	NAT2	C	T	0.67	6.28×10−15
Glycochenodeoxycholate 3-sulfate	Lipid	Primary bile metabolism	0.16	rs4149056	Missense	SLCO1B1	T	T	0.16	4.51×10−39
			0.01	rs11045913	Downstream gene	SLCO1A2	G	A	0.56	3.07×10−15
Decadienedioic acid (C10:2-DC)**	Lipid	Fatty acid, dicarboxylate	0.14	rs11621061	Intron	HEATR4	C	T	0.76	1.89×10−28
			0.04	rs58231493	Upstream gene	ACOT2	C	T	0.56	8.80×10−32
3-Amino-2-piperidone	Amino acid	Urea cycle; arginine and proline metabolism	0.13	rs37369	Missense	AGXT2	T	C	0.08	6.06×10−33
			0.04	rs16899974	Missense	AGXT2	A	C	0.22	9.31×10−17

Metabolite, metabolite annotation; super pathway, metabolite class annotation; subpathway, within class pathway annotation; variance explained, metabolite variance explained by genotype variation in mQTL SNP.

Total variance explained by mQTLs—metabolite variance explained by variation in all mQTL SNPs.

p-Value, p-value of regression test with SNP.

^*Indicates compounds that have not been officially confirmed based on a standard, but Metabolon is confident in its identity.

^**Indicates a compound for which a standard is not available, but Metabolon is confident in its identity or the information provided.

(#) or [#] indicates a compound that is a structural isomer of another compound in the Metabolon spectral library.

Ancestral allele, major allele; closest gene, closest gene to SNP as mapped in VEP; consequence, VEP annotation of variant; EAF, effect allele frequency in Discovery; effect allele, allele with positive association to metabolite; rsID, reference SNP ID number assigned by NCBI.

BCAA, branched chain amino acid; GPI, glycophosphatidylinositol; SNP, single-nucleotide polymorphism; VEP, Variant Effect Predictor.