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 77

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
Fibronectin cis Discovery rs1250258 2:216,300,185 T/C 0.25 996 -0.711 0.045 1.3×10-49 -1.100 5.8×10-48 2×10-46
Fibronectin cis Replication rs1250258 2:216,300,185 A/G 0.28 337 -0.600 0.083 4.4×10-12 -1.110 1×10-11 8.6×10-11
FN1.3 cis Discovery rs1250258 2:216,300,185 T/C 0.25 996 -0.668 0.047 1.8×10-42 -1.090 9.5×10-38 2.3×10-34
FN1.3 cis Replication rs1250258 2:216,300,185 A/G 0.28 337 -0.591 0.082 5.1×10-12 -1.110 6.7×10-11 3×10-10
FN1.4 cis Discovery rs1250258 2:216,300,185 T/C 0.25 996 -0.309 0.050 1.2×10-9 -1.040 1.9×10-9 1.1×10-9
FN1.4 cis Replication rs1250258 2:216,300,185 A/G 0.28 337 -0.373 0.071 3.3×10-7 -1.070 2.4×10-7 5.7×10-7

 

Regional association plots

 

Boxplots and histograms for top associations

Fibronectin

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

Fibronectin Fragment 3 (FN1.3)

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

Fibronectin Fragment 4 (FN1.4)

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

Fibronectin

Target (abbrv.) Fibronectin
Target (full name) Fibronectin
Somalogic ID (Sequence ID) SL000426 (4131-72_2)
Entrez Gene Symbol FN1
UniProt ID P02751
UniProt Comment
  • Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. Participates in the regulation of type I collagen deposition by osteoblasts.
Targeted by drugs (based on IPA annotation)
  • ocriplasmin
Biomarker applications (based on IPA annotation)
  • diagnosis
  • efficacy
  • prognosis
  • unspecified application
Wiki Pathways
  • Focal Adhesion
  • Inflammatory Response Pathway
  • Regulation of Actin Cytoskeleton
  • Senescence and Autophagy
Pathway Interaction Database
  • Alpha4 beta1 integrin signaling events
  • Alpha9 beta1 integrin signaling events
  • Angiopoietin receptor Tie2-mediated signaling
  • Beta1 integrin cell surface interactions
  • Beta3 integrin cell surface interactions
  • Beta5 beta6 beta7 and beta8 integrin cell surface interactions
  • Integrins in angiogenesis
  • Syndecan-2-mediated signaling events
  • Syndecan-4-mediated signaling events
  • Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
  • VEGFR3 signaling in lymphatic endothelium
Reactome
  • Cell surface interactions at the vascular wall
  • Degradation of the extracellular matrix
  • ECM proteoglycans
  • Extracellular matrix organization
  • Fibronectin matrix formation
  • GRB2:SOS provides linkage to MAPK signaling for Integrins
  • Integrin alphaIIb beta3 signaling
  • Integrin cell surface interactions
  • Molecules associated with elastic fibres
  • Non-integrin membrane-ECM interactions
  • Platelet degranulation
  • Syndecan interactions
  • p130Cas linkage to MAPK signaling for integrins
Pathway Studio
  • Extracellular Matrix Turnover
  • FibronectinR → AP-1/ELK-SRF/SREBF signaling
  • FibronectinR → CTNNB signaling
  • FibronectinR → ICAP-1A/MYC signaling
  • FibronectinR → NF-kB signaling
  • Focal Junction Assembly
  • Natural Killer Cell Activation through Integrins and non-ITAM-Containing Receptors

Fibronectin Fragment 3 (FN1.3)

Target (abbrv.) FN1.3
Target (full name) Fibronectin Fragment 3
Somalogic ID (Sequence ID) SL010349 (3434-34_1)
Entrez Gene Symbol FN1
UniProt ID P02751
UniProt Comment
  • Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. Participates in the regulation of type I collagen deposition by osteoblasts.
Targeted by drugs (based on IPA annotation)
  • ocriplasmin
Biomarker applications (based on IPA annotation)
  • diagnosis
  • efficacy
  • prognosis
  • unspecified application
Wiki Pathways
  • Focal Adhesion
  • Inflammatory Response Pathway
  • Regulation of Actin Cytoskeleton
  • Senescence and Autophagy
Pathway Interaction Database
  • Alpha4 beta1 integrin signaling events
  • Alpha9 beta1 integrin signaling events
  • Angiopoietin receptor Tie2-mediated signaling
  • Beta1 integrin cell surface interactions
  • Beta3 integrin cell surface interactions
  • Beta5 beta6 beta7 and beta8 integrin cell surface interactions
  • Integrins in angiogenesis
  • Syndecan-2-mediated signaling events
  • Syndecan-4-mediated signaling events
  • Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
  • VEGFR3 signaling in lymphatic endothelium
Reactome
  • Cell surface interactions at the vascular wall
  • Degradation of the extracellular matrix
  • ECM proteoglycans
  • Extracellular matrix organization
  • Fibronectin matrix formation
  • GRB2:SOS provides linkage to MAPK signaling for Integrins
  • Integrin alphaIIb beta3 signaling
  • Integrin cell surface interactions
  • Molecules associated with elastic fibres
  • Non-integrin membrane-ECM interactions
  • Platelet degranulation
  • Syndecan interactions
  • p130Cas linkage to MAPK signaling for integrins
Pathway Studio
  • Extracellular Matrix Turnover
  • FibronectinR → AP-1/ELK-SRF/SREBF signaling
  • FibronectinR → CTNNB signaling
  • FibronectinR → ICAP-1A/MYC signaling
  • FibronectinR → NF-kB signaling
  • Focal Junction Assembly
  • Natural Killer Cell Activation through Integrins and non-ITAM-Containing Receptors

Fibronectin Fragment 4 (FN1.4)

Target (abbrv.) FN1.4
Target (full name) Fibronectin Fragment 4
Somalogic ID (Sequence ID) SL010348 (3435-53_2)
Entrez Gene Symbol FN1
UniProt ID P02751
UniProt Comment
  • Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. Participates in the regulation of type I collagen deposition by osteoblasts.
Targeted by drugs (based on IPA annotation)
  • ocriplasmin
Biomarker applications (based on IPA annotation)
  • diagnosis
  • efficacy
  • prognosis
  • unspecified application
Wiki Pathways
  • Focal Adhesion
  • Inflammatory Response Pathway
  • Regulation of Actin Cytoskeleton
  • Senescence and Autophagy
Pathway Interaction Database
  • Alpha4 beta1 integrin signaling events
  • Alpha9 beta1 integrin signaling events
  • Angiopoietin receptor Tie2-mediated signaling
  • Beta1 integrin cell surface interactions
  • Beta3 integrin cell surface interactions
  • Beta5 beta6 beta7 and beta8 integrin cell surface interactions
  • Integrins in angiogenesis
  • Syndecan-2-mediated signaling events
  • Syndecan-4-mediated signaling events
  • Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
  • VEGFR3 signaling in lymphatic endothelium
Reactome
  • Cell surface interactions at the vascular wall
  • Degradation of the extracellular matrix
  • ECM proteoglycans
  • Extracellular matrix organization
  • Fibronectin matrix formation
  • GRB2:SOS provides linkage to MAPK signaling for Integrins
  • Integrin alphaIIb beta3 signaling
  • Integrin cell surface interactions
  • Molecules associated with elastic fibres
  • Non-integrin membrane-ECM interactions
  • Platelet degranulation
  • Syndecan interactions
  • p130Cas linkage to MAPK signaling for integrins
Pathway Studio
  • Extracellular Matrix Turnover
  • FibronectinR → AP-1/ELK-SRF/SREBF signaling
  • FibronectinR → CTNNB signaling
  • FibronectinR → ICAP-1A/MYC signaling
  • FibronectinR → NF-kB signaling
  • Focal Junction Assembly
  • Natural Killer Cell Activation through Integrins and non-ITAM-Containing Receptors

All locus annotations are based on the sentinel SNP (rs1250258) and 14 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
Potentially regulated genes
eQTL genes
  • FN1 fibronectin 1

 

Results from other genome-wide association studies

Trait P Study Source
cg10692870 (chr2:216300244) 1.6×10-81 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Gene expression of ATIC in peripheral blood monocytes 1.8×10-12 20502693 (PMID) GRASP2 eQTL
LDL cholesterol 3×10-8 24097068 (PMID) GWAS Catalog via SNiPA
Endometriosis (Stage III or IV disease) 3.2×10-8 21151130 (PMID) GRASP2 nonQTL
Triglycerides 2.4×10-7 24097068 (PMID) Supplemental file
Nonsyndromic striae distensae (stretch marks) 2.7×10-7 23633020 (PMID) GRASP2 nonQTL
cg11309217 (chr2:216299424) 2.1×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Endometriosis 1.7×10-5 21151130 (PMID) GRASP2 nonQTL
Total cholesterol 2.7×10-5 20686565 (PMID) GRASP2 nonQTL
Coronary artery disease (CAD) 2.3×10-4 23202125 (PMID) GRASP2 nonQTL
Coronary artery disease and myocardial infarction 2.3×10-4 23202125 (PMID) Supplemental file
Waist hip ratio 3.3×10-4 20935629 (PMID) GRASP2 nonQTL
Waist-to-hip ratio, adjusted for BMI 3.6×10-4 25673412 (PMID) Supplemental file