HelmholtzZentrum munich
WCMC

Connecting genetic risk to disease endpoints through the human blood plasma proteome

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 404

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
GOT1 trans Discovery rs757158 7:94,955,528 C/T 0.41 996 0.305 0.044 7×10-12 1.050 6.7×10-11 2.1×10-9
GOT1 trans Replication rs757158 7:94,955,528 A/G 0.49 337 -0.008 0.067 0.909 1.000 0.957 0.633

 

Regional association plots

Aspartate aminotransferase, cytoplasmic (GOT1)

 

Boxplots and histograms for top associations

Aspartate aminotransferase, cytoplasmic (GOT1)

inverse-normalized probe levels log2 transformed probe levels raw probe levels
Discovery study
Replication study

Aspartate aminotransferase, cytoplasmic (GOT1)

Target (abbrv.) GOT1
Target (full name) Aspartate aminotransferase, cytoplasmic
Somalogic ID (Sequence ID) SL000280 (4912-17_1)
Entrez Gene Symbol GOT1
UniProt ID P17174
UniProt Comment
  • Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain.
Wiki Pathways
  • Alanine and aspartate metabolism
  • Glycolysis and Gluconeogenesis
Reactome
  • Amino acid synthesis and interconversion (transamination)
  • Gluconeogenesis
  • Methionine salvage pathway

All locus annotations are based on the sentinel SNP (rs757158) and 1 proxy variant(s) that is/are in linkage disequilibrium r2 ≥ 0.8. Linkage disequilibrium is based on data from the 1000 Genomes Project, phase 3 version 5, European population and was retrieved using SNiPA's Block Annotation feature.
Download the detailed results of SNiPA's block annotation (PDF)

Linked genes

Genes hit or close-by
  • PON1 paraoxonase 1
eQTL genes
  • ASB4 ankyrin repeat and SOCS box containing 4
  • PON1 paraoxonase 1
  • PON2 paraoxonase 2

 

Results from other genome-wide association studies

Trait P Study Source
Serum arylesterase activity 3.7×10-116 22982463 (PMID) GRASP2 nonQTL
Paraoxonase activity 5×10-116 22982463 (PMID) GWAS Catalog via SNiPA
Serum paraoxonase activity 3.9×10-38 22982463 (PMID) GRASP2 nonQTL
cg21768566 (chr7:1265349) 5.7×10-19 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Methylation levels at chr7:94791589-94791639 [hg18 coord, probe cg07404485] in Caudal pons 6.8×10-16 20485568 (PMID) GRASP2 meQTL
Methylation levels at chr7:94791589-94791639 [hg18 coord, probe cg07404485] in Frontal cortex 2.7×10-15 20485568 (PMID) GRASP2 meQTL
Methylation levels at chr7:94791589-94791639 [hg18 coord, probe cg07404485] in Cerebellum 6.8×10-15 20485568 (PMID) GRASP2 meQTL
cg17332573 (chr6:26250910) 1.1×10-12 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Methylation levels at chr7:94791589-94791639 [hg18 coord, probe cg07404485] in Temporal cortex 1.9×10-12 20485568 (PMID) GRASP2 meQTL
Gene expression of PON1 in normal prepouch ileum 1.5×10-9 23474282 (PMID) GRASP2 eQTL
Gene expression of PON2 in blood 3.7×10-4 21829388 (PMID) GRASP2 eQTL