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WCMC

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

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Locus annotations

Locus 150

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
b-Endorphin trans Discovery rs12099358 11:116,726,048 C/A 0.16 995 -0.623 0.057 1.6×10-26 -1.180 8.7×10-12 0.115
b-Endorphin trans Replication rs12099358 11:116,726,048 C/A 0.20 337 -0.486 0.084 1.9×10-8 -1.140 8.5×10-6 0.007

 

Regional association plots

 

Boxplots and histograms for top associations

Beta-endorphin (b-Endorphin)

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

Beta-endorphin (b-Endorphin)

Target (abbrv.) b-Endorphin
Target (full name) Beta-endorphin
Somalogic ID (Sequence ID) SL000300 (2558-51_3)
Entrez Gene Symbol POMC
UniProt ID P01189
UniProt Comment
  • ACTH stimulates the adrenal glands to release cortisol.
Biomarker applications (based on IPA annotation)
  • diagnosis
  • efficacy
  • unspecified application
Pathway Interaction Database
  • Glucocorticoid receptor regulatory network
  • Syndecan-3-mediated signaling events
Reactome
  • Androgen biosynthesis
  • Defective ACTH causes Obesity and Pro-opiomelanocortinin deficiency (POMCD)
  • Endogenous sterols
  • G alpha (i) signalling events
  • G alpha (s) signalling events
  • G-protein activation
  • Glucocorticoid biosynthesis
  • Opioid Signalling
  • Peptide hormone biosynthesis
  • Peptide ligand-binding receptors
Pathway Studio
  • CRH → synthesis of corticosteroids
  • GALR1/2/3 → POMC/NPY production
  • NPY1R → CRH/POMC production
  • Nociception-related IL1B expression targets
  • OpioidR → CREB/ELK-SRF/STAT3 signaling
  • Summarized nociception-related expression targets

All locus annotations are based on the sentinel SNP (rs12099358) and 76 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
Potentially regulated genes
  • PCSK7 proprotein convertase subtilisin/kexin type 7
  • BUD13 BUD13 homolog (S. cerevisiae)
  • SIDT2 SID1 transmembrane family, member 2
  • SIK3 SIK family kinase 3
  • RNF214 ring finger protein 214
  • CEP164 centrosomal protein 164kDa
  • AP000936.4
eQTL genes
  • APOA1 apolipoprotein A-I
  • APOA1-AS APOA1 antisense RNA
  • SIDT2 SID1 transmembrane family, member 2

 

Results from other genome-wide association studies

Trait P Study Source
cg05256304 (chr11:116969846) 3.7×10-28 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Total cholesterol 6.9×10-16 20686565 (PMID) GRASP2 nonQTL
Triglycerides 8.4×10-14 23063622 (PMID) GRASP2 nonQTL
HDL cholesterol 2.5×10-10 20686565 (PMID) GRASP2 nonQTL
Triglycerides in males 3.9×10-10 23063622 (PMID) GRASP2 nonQTL
cg04048249 (chr11:116700580) 5.4×10-10 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
cg10753889 (chr11:116706544) 1.4×10-9 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Triglycerides in females 1.8×10-5 23063622 (PMID) GRASP2 nonQTL
2-palmitoylglycerophosphocholine* 2.4×10-5 24816252 (PMID) gwas.eu via SNiPA
1-oleoylglycerol (1-monoolein) 5.2×10-5 24816252 (PMID) gwas.eu via SNiPA
Height 6.2×10-5 25282103 (PMID) Supplemental file
Insulin secretion during OGTT 1.4×10-4 24699409 (PMID) Supplemental file
LDL cholesterol 4.4×10-4 20686565 (PMID) GRASP2 nonQTL

Possible link between cis-variants and protein levels of POMC.

This locus harbours a replicated trans-pQTL to Beta-endorphin (POMC).

The information gathered here is a result of an attempt to keep track of all interesting information that we encountered while investigating these loci. Please bear in mind that the annotation given here is neither complete nor free of errors, and that all information provided here should be confirmed by additional literature research before being used as a basis for firm conclusions or further experiments.