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WCMC

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

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Locus annotations

Locus 26

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 rs2304456 3:186,445,052 T/G 0.10 996 -1.366 0.058 2.9×10-97 -1.370 6.2×10-129 2.2×10-95
Kininogen, HMW cis Replication rs2304456 3:186,445,052 A/C 0.16 337 -1.159 0.075 2.8×10-40 -1.400 1.3×10-49 2.4×10-36
LCMT1 trans Discovery rs2304456 3:186,445,052 T/G 0.10 996 0.456 0.070 1.4×10-10 1.040 0.001 0.891
LCMT1 trans Replication rs5030044 3:186,449,122 A/G 0.16 337 0.380 0.077 1.5×10-6 1.090 9.1×10-5 0.001

 

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

Leucine carboxyl methyltransferase 1 (LCMT1)

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

Leucine carboxyl methyltransferase 1 (LCMT1)

Target (abbrv.) LCMT1
Target (full name) Leucine carboxyl methyltransferase 1
Somalogic ID (Sequence ID) SL011770 (4237-70_3)
Entrez Gene Symbol LCMT1
UniProt ID Q9UIC8
UniProt Comment
  • Methylates the carboxyl group of the C-terminal leucine residue of protein phosphatase 2A catalytic subunits to form alpha-leucine ester residues.

All locus annotations are based on the sentinel SNP (rs2304456) and 3 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