HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 178

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
IGFBP-3 cis Discovery rs2949833 7:45,984,820 C/T 0.29 993 0.428 0.043 2.6×10-22 1.100 1.2×10-18 2×10-19
IGFBP-3 cis Replication rs2949833 7:45,984,820 G/A 0.31 337 0.291 0.071 6×10-5 1.090 2.9×10-4 4.5×10-5
IGF-I trans Discovery rs2949833 7:45,984,820 C/T 0.29 993 0.320 0.045 3×10-12 1.050 3×10-10 2.2×10-8
IGF-I trans Replication rs2949833 7:45,984,820 G/A 0.31 337 0.147 0.052 0.005 1.050 0.003 0.006

 

Regional association plots

Insulin-like growth factor-binding protein 3 (IGFBP-3)

Insulin-like growth factor I (IGF-I)

 

Boxplots and histograms for top associations

Insulin-like growth factor-binding protein 3 (IGFBP-3)

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

Insulin-like growth factor I (IGF-I)

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

Insulin-like growth factor-binding protein 3 (IGFBP-3)

Target (abbrv.) IGFBP-3
Target (full name) Insulin-like growth factor-binding protein 3
Somalogic ID (Sequence ID) SL000045 (2571-12_3)
Entrez Gene Symbol IGFBP3
UniProt ID P17936
UniProt Comment
  • IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R.
Biomarker applications (based on IPA annotation)
  • diagnosis
  • disease progression
  • efficacy
  • prognosis
  • safety
Wiki Pathways
  • Myometrial Relaxation and Contraction Pathways
Pathway Interaction Database
  • Direct p53 effectors
  • Validated transcriptional targets of TAp63 isoforms
  • Validated transcriptional targets of deltaNp63 isoforms
Reactome
  • Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

Insulin-like growth factor I (IGF-I)

Target (abbrv.) IGF-I
Target (full name) Insulin-like growth factor I
Somalogic ID (Sequence ID) SL000047 (2952-75_2)
Entrez Gene Symbol IGF1
UniProt ID P05019
UniProt Comment
  • The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation (PubMed:21076856, PubMed:24132240). Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb (By similarity).
Biomarker applications (based on IPA annotation)
  • diagnosis
  • efficacy
  • prognosis
  • safety
Wiki Pathways
  • Adipogenesis
  • Apoptosis
  • Endochondral Ossification
  • Focal Adhesion
  • MicroRNAs in cardiomyocyte hypertrophy
  • Senescence and Autophagy
  • TarBasePathway
Reactome
  • IRS-related events triggered by IGF1R
  • Platelet degranulation
  • Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
  • SHC-related events triggered by IGF1R
  • Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
  • Synthesis, secretion, and deacylation of Ghrelin
Pathway Studio
  • IGF1R → CEBPA/FOXO1A signaling
  • IGF1R → ELK-SRF/HIF1A/MYC/SREBF signaling
  • IGF1R → MEF/MYOD/MYOG signaling
  • IGF1R → STAT signaling

All locus annotations are based on the sentinel SNP (rs2949833) 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

eQTL genes
  • IGFBP3 insulin-like growth factor binding protein 3

 

Results from other genome-wide association studies

Trait P Study Source
Waist circumfence, adjusted for BMI 1.2×10-4 25673412 (PMID) Supplemental file

Functional match between insulin-like growth factor-binding protein in cis and insulin-like growth factor in trans.

This locus harbours a replicated cis-association with insulin-like growth factor-binding protein 3 (IGFBP3) levels. A trans-association with insulin-like growth factor I (IGF1) levels was only nominal in QMDiab (p=5.1×10-3). Both associations display the same directionality. This locus replicates Kaplan et al. [PubMed] association of SNP rs11977526 (chr7:46008110) (IGFBP3) with IGF-I levels. Confirms strong GWAS hits.

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.