HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 288

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
Kininogen, HMW cis Discovery rs3856930 3:186,458,322 C/T 0.35 994 0.353 0.045 7.6×10-15 1.080 2.2×10-15 1.7×10-13
Kininogen, HMW cis Replication rs5030060 3:186,452,917 G/A 0.23 337 0.092 0.086 0.287 1.020 0.366 0.418

 

Regional association plots

 

Boxplots and histograms for top associations

Kininogen-1 (Kininogen, HMW)

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

Kininogen-1 (Kininogen, HMW)

Target (abbrv.) Kininogen, HMW
Target (full name) Kininogen-1
Somalogic ID (Sequence ID) SL017189 (4495-33_2)
Entrez Gene Symbol KNG1
UniProt ID P01042
UniProt Comment
  • (1) Kininogens are inhibitors of thiol proteases; (2) HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting.
Wiki Pathways
  • ACE Inhibitor Pathway
  • Complement and Coagulation Cascades
Pathway Interaction Database
  • Beta2 integrin cell surface interactions
  • Syndecan-2-mediated signaling events
Reactome
  • G alpha (i) signalling events
  • G alpha (q) signalling events
  • Intrinsic Pathway of Fibrin Clot Formation
  • Peptide ligand-binding receptors
  • Platelet degranulation
Pathway Studio
  • BDKRB1/2 → interleukins production
  • BDKRB1/2 → ion channels
  • BDKRB1/2 → prostaglandin generation
  • BDKRB1/2 → vasodilation
  • Coagulation Cascade

All locus annotations are based on the sentinel SNP (rs3856930) and 4 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

 

Results from other genome-wide association studies

Trait P Study Source
Activated partial thromboplastin time 4×10-136 22703881 (PMID) GRASP2 nonQTL
bradykinin, des-arg(9) 1.4×10-12 24816252 (PMID) gwas.eu via SNiPA
Adiponectin levels 2.3×10-10 22479202 (PMID) GRASP2 nonQTL
Adiponectin levels (female) 2×10-9 22479202 (PMID) GRASP2 nonQTL