HelmholtzZentrum munich

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


Proteome annotation
Locus annotations

Locus 269

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
sTie-1 trans Discovery rs630510 9:136,149,581 G/A 0.47 994 -0.350 0.043 1.6×10-15 -1.060 5.4×10-15 8.5×10-15
sTie-1 trans Replication rs630014 9:136,149,722 G/A 0.44 337 -0.392 0.060 2.4×10-10 -1.100 6.1×10-10 6.4×10-10


Regional association plots

Tyrosine-protein kinase receptor Tie-1, soluble (sTie-1)


Boxplots and histograms for top associations

Tyrosine-protein kinase receptor Tie-1, soluble (sTie-1)

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

Tyrosine-protein kinase receptor Tie-1, soluble (sTie-1)

Target (abbrv.) sTie-1
Target (full name) Tyrosine-protein kinase receptor Tie-1, soluble
Somalogic ID (Sequence ID) SL003199 (2844-53_2)
Entrez Gene Symbol TIE1
UniProt ID P35590
UniProt Comment
  • Transmembrane tyrosine-protein kinase that may modulate TEK/TIE2 activity and contribute to the regulation of angiogenesis.

All locus annotations are based on the sentinel SNP (rs630510) 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
  • ABO ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase)
Potentially regulated genes
  • CELP carboxyl ester lipase pseudogene
  • DBH dopamine beta-hydroxylase (dopamine beta-monooxygenase)
  • ADAMTSL2 ADAMTS-like 2
  • SARDH sarcosine dehydrogenase
  • RALGDS ral guanine nucleotide dissociation stimulator
eQTL genes
  • ABO ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase)
  • MED22 mediator complex subunit 22


Results from other genome-wide association studies

Trait P Study Source
von Willebrand factor (vWF) 6.7×10-87 21534939 (PMID) GRASP2 nonQTL
Activated partial thromboplastin time 1.9×10-46 22703881 (PMID) GRASP2 nonQTL
Soluble intercellular adhesion molecule 1 (ICAM-1) 1.5×10-22 21533024 (PMID) GRASP2 nonQTL
Venous thrombosis 2.5×10-19 21980494 (PMID) GRASP2 nonQTL
TNF-alpha (TNF-a) 5.4×10-17 18464913 (PMID) GRASP2 nonQTL
LDL cholesterol 2.1×10-16 24097068 (PMID) Supplemental file
Triglycerides 6.4×10-16 24097068 (PMID) Supplemental file
Gene expression of MED22 in blood 4.7×10-15 21829388 (PMID) GRASP2 eQTL
Factor XIII antigen 1.7×10-14 23381943 (PMID) GRASP2 nonQTL
Gene expression of ABO (probeID ILMN_1656979) in temporal cortex in Alzheimer's disease cases and controls 7.9×10-13 22685416 (PMID) GRASP2 eQTL
Serum soluble E-selectin 9.6×10-13 19729612 (PMID) GRASP2 nonQTL
E-selectin 9.7×10-13 pha002871 (dbGaP) dbGaP via SNiPA
Interleukin-6 (IL-6) levels 1.1×10-9 22291609 (PMID) GRASP2 nonQTL
ADpSGEGDFXAEGGGVR* 3.5×10-9 24816252 (PMID) gwas.eu via SNiPA
cg06818865 (chr9:136151982) 4.8×10-9 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Gene expression of ABO in normal prepouch ileum 6.6×10-9 23474282 (PMID) GRASP2 eQTL
Gene expression of SURF6 in blood 1.2×10-8 21829388 (PMID) GRASP2 eQTL
Venous thromboembolism (VTE) 1.2×10-8 19278955 (PMID) GRASP2 nonQTL
Circulating galectin-3 levels 2.8×10-8 23056639 (PMID) GRASP2 nonQTL
Hematocrit (Hct) 3.7×10-8 23222517 (PMID) GRASP2 nonQTL
Venous thromboembolism 3.9×10-8 22672568 (PMID) GRASP2 nonQTL
Pancreatic cancer 6.3×10-8 19648918 (PMID) GRASP2 nonQTL
Total cholesterol 1.2×10-7 23063622 (PMID) GRASP2 nonQTL
Pancreatic neoplasms 4.7×10-6 pha002889 (dbGaP) dbGaP via SNiPA
Graves' disease 8.2×10-6 23612905 (PMID) GRASP2 nonQTL
Grave's disease 8.5×10-6 21841780 (PMID) GRASP2 nonQTL
Simpson-Angus Scale 9.8×10-6 19875103 (PMID) GRASP2 nonQTL
Gene expression of ABO (probeID ILMN_1656979) in cerebellum in Alzheimer's disease cases and controls 1.1×10-5 22685416 (PMID) GRASP2 eQTL
Gene expression of SURF1 [probe ILMN_2148] in osteoblasts treated with dexamethasone 1.8×10-5 21283786 (PMID) GRASP2 eQTL
cg13660174 (chr9:136238416) 7.8×10-5 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Coronary artery disease (CAD) 1.1×10-4 23202125 (PMID) GRASP2 nonQTL
Coronary artery disease and myocardial infarction 2.5×10-4 23202125 (PMID) Supplemental file

The pleiotropic ABO locus is discussed in the main paper.

This locus is discussed in the main paper. Here we report observations not mentioned in the paper: In Shin et al. [PubMed] SNP rs651007 associates with dipeptide levels (aspartylphenylalanine, p=2×10-7; X-14189, annotated as potential Leu-Ala, but Ser-Pro is also possible by mass alone, p=9.6×10-10; X14304, I/L-Ala or Ala-I/L?, p=1.8×10-8; X-14208, could be Cys-Met or Tyr-Ala or His-Pro or Ser-Phe by mass alone, p=1.5×10-7; X-14205; X14086: annotated as Thr-Glu, but mass is 25 too high; Val-Arg possible by mass alone). This SNP also associates in Raffler et al. [PubMed] (Urine NMR) with a signal at 2.0308 ppm (PM20308, p=5.1×10-20). It is also a marginal hit in CardioGram (7.1×10-8). He et al. [PubMed] report a genome wide association study of genetic loci that influence tumour biomarkers cancer antigen 19-9, carcinoembryonic antigen and α fetoprotein and their associations with cancer risk. The authors find strong association of SNP rs8176749 with carcinoembryonic antigen (CEA) levels – we find association with Cadherin-5. CD209 and MBL2 are both lectins. All associated ABO-associated proteins are glycoproteins, part of glycoprotein complex (LY96), or glycoprotein-binding (SELE), except for IL27RA (http://jcggdb.jp/rcmg/gpdb/index). According to Uniprot all proteins are glycoproteins (including associations non-replicated in QMDiab), while only half of all SomaLogic proteins are glycoproteins. The Panther classification system (http://pantherdb.org/tools/compareToRefList.jsp) reported a significant enrichment of the GO process "endothelial cell differentiation" (GO:0045446): 5 out of 17 annotated proteins were found (expected were 0.32, p=1.45×10-5).

Subnetwork of the ABO locus.Six replicated pQTLs at the ABO gene locus (red), including SNP identifiers that are linked to the the six loci (light green KORA SNPs, yellow QMDiab SNPs, bright green both), pQTLS (blue), proteins with significant partial correlation are connected, associations with GWAS endpoints are shown (grey) [NOTE: the anorexia is a false positive, checked this with the consortium].

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.