Liver enzymes, metabolomics and genome-wide association studies: From systems biology to the personalized medicine

Table 4 Summary of the variants associated with alanine-aminotransferase and aspartate-aminotransferase levels in population-based genome-wide association studies: Biological function and variants characteristics

Variant ID	Variant features	Significant P value for GWAS association	Gene or nearest gene	Reported biological function of the associated locus
ALT
rs6834314	Intergenic	3.1 × 10-9	HSD17B13/MAPK10	Oxidoreductase involved in the metabolism of steroid hormones, prostaglandins, retinoids, lipids and xenobiotics
				A member of the MAP kinase family
rs2954021	Intron variant	5.3 × 10-9	TRIB1	Involved in protein amino acid phosphorylation and controlling mitogen-activated protein kinase cascades. Potent negative regulator of MAPK pathways influencing apoptosis. Regulates hepatic lipogenesis and very low density lipoprotein production
rs10883437	Intergenic	4.0 × 10-9	CPN1	A plasma metallo-protease that cleaves basic amino acids from the C terminal of peptides and proteins
rs11597390	intergenic	2.9 × 10-8
rs738409	Missense	1.2 × 10-45	PNPLA3	Acylglycerol O-acyltransferase and triacylglycerol lipase that mediates triacylglycerol hydrolysis
	p.Ile148Met
rs2281135	Intron variant	8.2 × 10-12
rs3761472	Missense	3.7 × 10-29	SAMM50	Component of the sorting and assembly machinery (SAM) of the mitochondrial outer membrane
	p.Asp110Gly
rs2143571	Intron variant	9.4 × 10-7
rs11597086	Non coding exon variant	3.6 × 10-7	CHUK	Member of the serine/threonine protein kinase family; a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex
rs11591741	Intron variant	4.5 × 10-7
rs4949718	Intron variant	1.87 × 10-7	ST6GALNAC3	Transfer sialic acids from CMP-sialic acid to terminal positions of carbohydrate groups in glycoproteins and glycolipids
rs17801127	Intergenic	2.37 × 10-7	MMADHC	Mitochondrial protein that is involved in an early step of vitamin B12 metabolism
rs1539893	Intron variant	3.40 × 10-6	CCDC102BRGS5	Unknown Member of the regulators of G protein signaling (RGS) family
rs12035879	Intron variant	3.97 × 10-6
rs9941219	Intergenic	4.06 × 10-6	BRD7	Member of the bromodomain-containing protein family
rs731660	Intergenic
rs12621256	Intron variant	4.36 × 10-6	GALNT13	Member of the glycosyltransferase 2 family; catalyzes the initial reaction in oligosaccharide biosynthesis; neurons cell biogenesis
rs6035126	Intergenic	4.94 × 10-6	SIRPA	Receptor-type transmembrane glycoproteins involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes
rs13433286	Intergenic
rs844917	Intergenic	5.64 × 10-6	CD93	Cell-surface glycoprotein and type I membrane protein
rs844914	Intergenic	5.98 × 10-6
rs903107	Intron variant	6.11 × 10-6	SLC39A11	Mediates zinc uptake
rs80311637	Missense p.Val653Met	7.18 × 10-6	ADAMTS9	Disintegrin and metalloproteinase with thrombospondin motifs
rs596406	Intron variant	9.18 × 10-6	CELF2	RNA-binding protein implicated in the regulation of several post-transcriptional events
AST
rs11597390	Intergenic	0.0009	CHUK	Explained previously
rs2281135	Intron variant	5.7 × 10-6	PNPLA3	Explained previously
rs862946	Intergenic	2.41 × 10-7	CYB5AP5	Pseudogene
rs596406	Intron variant	3.69 × 10-7	CELF2	Explained previously
rs76850691	Missense p.Gln349Glu	8.55 × 10-7	GOT1	Biosynthesis of L-glutamate from L-aspartate or L-cysteine
rs17109512	Intergenic	2.80 × 10-14
rs4949718	Intron variant	1.49 × 10-6	ST6GALNAC3	Explained previously
rs80311637	Missense p.Val1597Met	1.85 × 10-6	ADAMTS9	Explained previously
rs892877	Intron variant	3.75 × 10-6	THSD7B	Unknown
rs984295	Intron variant	5.86 × 10-6
rs457603	Intergenic	4.57 × 10-6	EIF4A1P1	Pseudogene
rs452621	Intergenic
rs7617400	Intron variant	6.16 × 10-6	ROBO1	Neuronal development
rs11924965	Intron variant
rs7644918	Intron variant

HSD17B13: Hydroxysteroid (17-beta) dehydrogenase 13; MAPK10: Mitogen-activated protein kinase 10; TRIB1: Tribbles pseudokinase 1; CPN1: Carboxypeptidase N, polypeptide 1; PNPLA3: Patatin-like phospholipase domain containing 3; SAMM50: Sorting and assembly machinery component; CHUK: Conserved helix-loop-helix ubiquitous kinase; ST6GALNAC3: ST6 (alpha-N-acetyl-neuraminyl-2,3-beta-galactosyl-1,3)-N-acetylgalactosaminide alpha-2,6-sialyltransferase 3; MMADHC: Methylmalonic aciduria (cobalamin deficiency) cblD type, with homocystinuria; CCDC102B: Coiled-Coil Domain Containing 102B; RGS5: Regulator of G-protein signaling 5; BRD7: Bromodomain containing 7; GALNT13: Polypeptide N-acetylgalactosaminyltransferase 13; SIRPA: Signal-regulatory protein alpha; CD93: CD93 molecule; SLC39A11: Solute carrier family 39, member 11; ADAMTS9: ADAM metallopeptidase with thrombospondin type 1 motif, 9; CYB5AP5: Cytochrome b5 type A (microsomal) pseudogene 5; CELF2: CUGBP, Elav-like family member 2; GOT1: Glutamic-oxaloacetic transaminase 1, soluble; THSD7B: thrombospondin, type I, domain containing 7B; EIF4A1P1: Eukaryotic translation initiation factor 4A1 pseudogene 1; ROBO1: Roundabout, axon guidance receptor, homolog 1. Biological function was extracted from Gene Atlas (http://genatlas.medecine.univ-paris5.fr).