HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Home
Ideogram
Loci
Network view
Proteome annotation
Help
Locus annotations

Locus 69

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
Cadherin-5 trans Discovery rs8176749 9:136,131,188 C/T 0.09 995 1.108 0.068 6.1×10-53 1.240 1.2×10-55 1.3×10-52
Cadherin-5 trans Replication rs8176693 9:136,137,657 G/A 0.16 337 0.933 0.059 2.7×10-42 1.240 2.9×10-42 3.5×10-40
sTie-1 trans Discovery rs8176749 9:136,131,188 C/T 0.09 995 1.099 0.069 1.7×10-51 1.210 5.8×10-51 1×10-57
sTie-1 trans Replication rs8176743 9:136,131,415 G/A 0.17 337 0.804 0.068 3.5×10-27 1.220 10×10-26 1.2×10-25
sTie-2 trans Discovery rs8176749 9:136,131,188 C/T 0.09 995 0.906 0.070 1.1×10-35 1.130 2.2×10-36 8.7×10-38
sTie-2 trans Replication rs8176693 9:136,137,657 G/A 0.16 337 0.496 0.075 2×10-10 1.090 5.6×10-10 3.4×10-9
Endoglin cis Discovery rs8176749 9:136,131,188 C/T 0.09 995 0.629 0.074 5.6×10-17 1.130 1.4×10-16 3.9×10-18
Endoglin cis Replication rs8176743 9:136,131,415 G/A 0.17 337 0.260 0.072 3.4×10-4 1.100 0.002 0.092
BCAM trans Discovery rs8176749 9:136,131,188 C/T 0.09 995 0.506 0.074 1.5×10-11 1.090 7.7×10-8 0.08
BCAM trans Replication rs8176693 9:136,137,657 G/A 0.16 337 0.282 0.069 5.8×10-5 1.070 2.7×10-4 0.001
CD109 trans Discovery rs8176749 9:136,131,188 C/T 0.09 995 0.509 0.075 1.7×10-11 1.120 1.8×10-10 9.2×10-9
CD109 trans Replication rs8176693 9:136,137,657 G/A 0.16 337 0.260 0.074 4.8×10-4 1.110 3.1×10-4 0.001
VEGF sR3 trans Discovery rs8176749 9:136,131,188 C/T 0.09 995 0.492 0.075 7.9×10-11 1.110 1.2×10-9 9.9×10-11
VEGF sR3 trans Replication rs77693339 9:136,128,558 A/G 0.16 337 0.237 0.087 0.007 1.060 0.009 0.01
TCCR trans Discovery rs8176749 9:136,131,188 C/T 0.09 995 0.492 0.075 8.3×10-11 1.130 1.9×10-9 0.004
TCCR trans Replication rs8176743 9:136,131,415 G/A 0.17 337 0.221 0.093 0.017 1.030 0.278 0.799
Notch 1 cis Discovery rs8176749 9:136,131,188 C/T 0.09 995 0.448 0.072 6×10-10 1.050 2.3×10-9 6.4×10-10
Notch 1 cis Replication rs8176743 9:136,131,415 G/A 0.17 337 0.235 0.051 5.3×10-6 1.040 3.1×10-6 8.9×10-6

 

Regional association plots

 

Boxplots and histograms for top associations

Cadherin-5

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

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

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

Angiopoietin-1 receptor, soluble (sTie-2)

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

Endoglin

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

Basal Cell Adhesion Molecule (BCAM)

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

CD109 antigen (CD109)

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

Vascular endothelial growth factor receptor 3 (VEGF sR3)

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

Interleukin-27 receptor subunit alpha (TCCR)

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

Neurogenic locus notch homolog protein 1 (Notch 1)

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

Cadherin-5

Target (abbrv.) Cadherin-5
Target (full name) Cadherin-5
Somalogic ID (Sequence ID) SL002081 (2819-23_2)
Entrez Gene Symbol CDH5
UniProt ID P33151
UniProt Comment
  • Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. This cadherin may play a important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. It associates with alpha-catenin forming a link to the cytoskeleton. Acts in concert with KRIT1 to establish and maintain correct endothelial cell polarity and vascular lumen. These effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for activation of PRKCZ and for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction.
Biomarker applications (based on IPA annotation)
  • diagnosis
Pathway Interaction Database
  • S1P2 pathway
  • Signaling events mediated by VEGFR1 and VEGFR2
Reactome
  • Adherens junctions interactions
  • VEGFR2 mediated vascular permeability
Pathway Studio
  • Leukocyte Adhesion to Endothelial Cell

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.

Angiopoietin-1 receptor, soluble (sTie-2)

Target (abbrv.) sTie-2
Target (full name) Angiopoietin-1 receptor, soluble
Somalogic ID (Sequence ID) SL003200 (3773-15_4)
Entrez Gene Symbol TEK
UniProt ID Q02763
UniProt Comment
  • Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1.
Targeted by drugs (based on IPA annotation)
  • cabozantinib
  • regorafenib
  • ponatinib
  • cabozantinib/erlotinib
  • vandetanib
Biomarker applications (based on IPA annotation)
  • efficacy
Wiki Pathways
  • Angiogenesis
  • Wnt Signaling Pathway
  • angiogenesis overview
Pathway Interaction Database
  • Angiopoietin receptor Tie2-mediated signaling
  • SHP2 signaling
Reactome
  • Tie2 Signaling
Pathway Studio
  • AngiopoietinR → AP-1 signaling
  • AngiopoietinR → FOXO signaling
  • AngiopoietinR → STAT signaling

Endoglin

Target (abbrv.) Endoglin
Target (full name) Endoglin
Somalogic ID (Sequence ID) SL004482 (4908-6_1)
Entrez Gene Symbol ENG
UniProt ID P17813
UniProt Comment
  • Major glycoprotein of vascular endothelium. Involved in the regulation of angiogenesis. May play a critical role in the binding of endothelial cells to integrins and/or other RGD receptors. Acts as TGF-beta coreceptor and is involved in the TGF-beta/BMP signaling cascade. Required for GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates TGF-beta1 signaling through SMAD3.
Biomarker applications (based on IPA annotation)
  • disease progression
  • efficacy
Wiki Pathways
  • TGF Beta Signaling Pathway
Pathway Interaction Database
  • ALK1 signaling events
  • HIF-1-alpha transcription factor network

Basal Cell Adhesion Molecule (BCAM)

Target (abbrv.) BCAM
Target (full name) Basal Cell Adhesion Molecule
Somalogic ID (Sequence ID) SL001902 (2816-50_2)
Entrez Gene Symbol BCAM
UniProt ID P50895
UniProt Comment
  • Laminin alpha-5 receptor. May mediate intracellular signaling.
Biomarker applications (based on IPA annotation)
  • diagnosis

CD109 antigen (CD109)

Target (abbrv.) CD109
Target (full name) CD109 antigen
Somalogic ID (Sequence ID) SL008773 (3290-50_2)
Entrez Gene Symbol CD109
UniProt ID Q6YHK3
UniProt Comment
  • Modulates negatively TGFB1 signaling in keratinocytes.

Vascular endothelial growth factor receptor 3 (VEGF sR3)

Target (abbrv.) VEGF sR3
Target (full name) Vascular endothelial growth factor receptor 3
Somalogic ID (Sequence ID) SL003322 (2358-19_2)
Entrez Gene Symbol FLT4
UniProt ID P35916
UniProt Comment
  • Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'.
Targeted by drugs (based on IPA annotation)
  • sunitinib
  • pazopanib
  • axitinib
  • CEP 7055
  • tivozanib
  • motesanib
  • telatinib
  • cabozantinib
  • nintedanib
  • regorafenib
  • bortezomib/sorafenib
  • dexamethasone/lenalidomide/sorafenib
  • bevacizumab/sorafenib
  • cabozantinib/erlotinib
  • sorafenib
  • vandetanib
Biomarker applications (based on IPA annotation)
  • diagnosis
  • disease progression
  • efficacy
  • prognosis
Pathway Interaction Database
  • VEGF and VEGFR signaling network
  • VEGFR3 signaling in lymphatic endothelium
Reactome
  • VEGF binds to VEGFR leading to receptor dimerization
Pathway Studio
  • VEGFR → AP-1/CREB/MYC signaling
  • VEGFR → ATF/CREB/ELK-SRF signaling
  • VEGFR → CTNNB signaling
  • VEGFR → FOXO3A signaling

Interleukin-27 receptor subunit alpha (TCCR)

Target (abbrv.) TCCR
Target (full name) Interleukin-27 receptor subunit alpha
Somalogic ID (Sequence ID) SL005223 (5132-71_3)
Entrez Gene Symbol IL27RA
UniProt ID Q6UWB1
UniProt Comment
  • Receptor for IL27. Requires IL6ST/gp130 to mediate signal transduction in response to IL27. This signaling system acts through STAT3 and STAT1. Involved in the regulation of Th1-type immune responses. Also appears to be involved in innate defense mechanisms.
Pathway Interaction Database
  • IL27-mediated signaling events
Pathway Studio
  • Th1 Cell Differentiation

Neurogenic locus notch homolog protein 1 (Notch 1)

Target (abbrv.) Notch 1
Target (full name) Neurogenic locus notch homolog protein 1
Somalogic ID (Sequence ID) SL005703 (5107-7_2)
Entrez Gene Symbol NOTCH1
UniProt ID P46531
UniProt Comment
  • Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4+ and CD8+ cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO).
Biomarker applications (based on IPA annotation)
  • diagnosis
  • efficacy
Wiki Pathways
  • Epithelium TarBase
  • Heart Development
  • Lymphocyte TarBase
  • Muscle cell TarBase
  • Neural Crest Differentiation
  • Notch Signaling Pathway
  • Proteins and DNA Sequences in Cardicac Structures
Pathway Interaction Database
  • Notch signaling pathway
  • Notch-mediated HES/HEY network
  • Presenilin action in Notch and Wnt signaling
  • Validated transcriptional targets of deltaNp63 isoforms
Reactome
  • Activated NOTCH1 Transmits Signal to the Nucleus
  • Constitutive Signaling by NOTCH1 HD Domain Mutants
  • Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
  • Constitutive Signaling by NOTCH1 PEST Domain Mutants
  • Constitutive Signaling by NOTCH1 t(7
  • Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling
  • NOTCH1 Intracellular Domain Regulates Transcription
  • Notch-HLH transcription pathway
  • Pre-NOTCH Processing in Golgi
  • Pre-NOTCH Processing in the Endoplasmic Reticulum
  • Pre-NOTCH Transcription and Translation
  • Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells
Pathway Studio
  • Adherens Junction Assembly (Cadherins)
  • EphrinR → STAT signaling
  • Model of T-cell Maturation
  • Notch → EP300/ASCL signaling
  • Notch → LEF1 signaling
  • Notch → MEF/MYOD signaling
  • Notch → NF-kB signaling
  • Notch → SMAD3 signaling
  • Notch → TCF3 signaling
  • Transcriptional Activation of Immunoglobulin Genes

All locus annotations are based on the sentinel SNP (rs8176749) and 24 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)
  • Y_RNA
  • LCN1P2 lipocalin 1 pseudogene 2
Potentially regulated genes
  • DBH dopamine beta-hydroxylase (dopamine beta-monooxygenase)
  • SURF2
  • SURF2 surfeit 2
  • ADAMTSL2 ADAMTS-like 2
  • ADAMTS13
  • GFI1B growth factor independent 1B transcription repressor
  • CELP carboxyl ester lipase pseudogene
  • SURF1 surfeit 1
  • SURF1
  • ADAMTS13 ADAM metallopeptidase with thrombospondin type 1 motif, 13
  • SARDH sarcosine dehydrogenase
  • RALGDS ral guanine nucleotide dissociation stimulator
  • OBP2B
  • OBP2B odorant binding protein 2B
  • SURF4
  • ABO ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase)
  • SURF4 surfeit 4
  • C9orf9 chromosome 9 open reading frame 9
  • REXO4 REX4, RNA exonuclease 4 homolog (S. cerevisiae)
  • AK8 adenylate kinase 8
  • REXO4
  • GTF3C5 general transcription factor IIIC, polypeptide 5, 63kDa
eQTL genes
  • ABO ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase)
  • OBP2B odorant binding protein 2B
  • MED22 mediator complex subunit 22
  • SLC2A6 solute carrier family 2 (facilitated glucose transporter), member 6

 

Results from other genome-wide association studies

Trait P Study Source
Coagulation factor levels 2×10-138 23267103 (PMID) GWAS Catalog via SNiPA
Tumor biomarkers 7×10-105 23300138 (PMID) GWAS Catalog via SNiPA
Plasma carcinoembryonic antigen (CEA) levels 7.2×10-105 23300138 (PMID) GRASP2 nonQTL
Metabolic syndrome domains (Multivariate analysis) 6.1×10-75 22022282 (PMID) GRASP2 nonQTL
von Willebrand factor (vWF) 4.4×10-36 23267103 (PMID) GRASP2 nonQTL
cg07241568 (chr9:136150847) 9.8×10-31 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Elevated serum carcinoembryonic antigen levels 2×10-24 24941225 (PMID) GWAS Catalog via SNiPA
Activated partial thromboplastin time 2.9×10-23 22703881 (PMID) GRASP2 nonQTL
High serum lipase activity 1×10-22 25028398 (PMID) GWAS Catalog via SNiPA
Hemoglobin (Hb) 1.1×10-17 23222517 (PMID) GRASP2 nonQTL
End-stage coagulation 2×10-17 23381943 (PMID) GWAS Catalog via SNiPA
Factor XIII antigen 1.2×10-14 23381943 (PMID) GRASP2 nonQTL
TNF-alpha (TNF-a) 2×10-14 18464913 (PMID) GRASP2 nonQTL
Red blood cell count (RBC) 1.6×10-13 23222517 (PMID) GRASP2 nonQTL
Urinary metabolites (H-NMR features) 4×10-12 24586186 (PMID) GWAS Catalog via SNiPA
LDL cholesterol 2.2×10-11 24097068 (PMID) Supplemental file
Intraocular pressure 3×10-11 25173106 (PMID) GWAS Catalog via SNiPA
Gene expression of MED22 in peripheral blood monocytes 1.8×10-10 20502693 (PMID) GRASP2 eQTL
Angiotensin-converting enzyme (ACE) activity 2.9×10-10 20066004 (PMID) GRASP2 nonQTL
Malaria 3.7×10-8 23717212 (PMID) GRASP2 nonQTL
Mean corpuscular hemoglobin concentration 4×10-8 20139978 (PMID) GWAS Catalog via SNiPA
Mean corpuscular hemoglobin concentration (MCHC) 4.3×10-8 20139978 (PMID) GRASP2 nonQTL
Hematocrit (Hct) 5.4×10-8 23222517 (PMID) GRASP2 nonQTL
Gene expression of ABO (probeID ILMN_1656979) in temporal cortex in Alzheimer's disease cases and controls 7.1×10-8 22685416 (PMID) GRASP2 eQTL
Circulating galectin-3 levels 7.6×10-8 23056639 (PMID) GRASP2 nonQTL
cg23778596 (chr7:149411474) 9.8×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Mean corpuscular volume (MCV) 1.5×10-7 23222517 (PMID) GRASP2 nonQTL
Gene expression of SURF6 in peripheral blood monocytes 2.8×10-7 20502693 (PMID) GRASP2 eQTL
Gene expression of ABO (probeID ILMN_1656979) in temporal cortex in Alzheimer's disease cases 2×10-6 22685416 (PMID) GRASP2 eQTL
Gene expression of ABO in CD4+ lymphocytes 2.8×10-6 20833654 (PMID) GRASP2 eQTL
Graves' disease 4×10-6 23612905 (PMID) GRASP2 nonQTL
Parkinson disease 8.7×10-6 pha002868 (dbGaP) dbGaP via SNiPA
Parkinson's disease (PD) 8.7×10-6 19915575 (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 ABO in normal prepouch ileum 1.2×10-5 23474282 (PMID) GRASP2 eQTL
Gene expression of ABO (probeID ILMN_1656979) in cerebellum in Alzheimer's disease cases 1.2×10-5 22685416 (PMID) GRASP2 eQTL
HDL cholesterol 2.1×10-5 24097068 (PMID) Supplemental file
Grave's disease 2.6×10-5 21841780 (PMID) GRASP2 nonQTL
Esophageal squamous cell carcinoma (Esophageal cancer) 7.1×10-5 23300138 (PMID) GRASP2 nonQTL
Autism 1.5×10-4 20663923 (PMID) GRASP2 nonQTL
Chronic kidney disease 4.8×10-4 20383146 (PMID) GRASP2 nonQTL

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.