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WCMC

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

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Locus annotations

Locus 1

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
sICAM-1 cis Discovery rs5498 19:10,395,683 A/G 0.43 997 -1.217 0.025 7.7×10-267 -1.400 1.1×10-294 5.6×10-276
sICAM-1 cis Replication rs923366 19:10,397,223 G/A 0.44 337 -1.112 0.040 1.1×10-88 -1.700 1.1×10-99 3.3×10-76
sICAM-5 cis Discovery rs5498 19:10,395,683 A/G 0.43 997 0.511 0.042 2.4×10-32 1.130 5.3×10-31 1.8×10-24
sICAM-5 cis Replication rs901886 19:10,402,131 A/G 0.47 337 0.538 0.057 8.2×10-19 1.150 1.6×10-18 1.2×10-16

 

Regional association plots

Intercellular adhesion molecule 1 (sICAM-1)

Download the association data used to generate this plot

Intercellular adhesion molecule 5 (sICAM-5)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

Intercellular adhesion molecule 1 (sICAM-1)

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

Intercellular adhesion molecule 5 (sICAM-5)

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

Intercellular adhesion molecule 1 (sICAM-1)

Target (abbrv.) sICAM-1
Target (full name) Intercellular adhesion molecule 1
Somalogic ID (Sequence ID) SL002922 (4342-10_3)
Entrez Gene Symbol ICAM1
UniProt ID P05362
UniProt Comment
  • ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation.
Biomarker applications (based on IPA annotation)
  • diagnosis
  • efficacy
  • prognosis
  • unspecified application
Wiki Pathways
  • Folate Metabolism
  • RANKL/RANK Signaling Pathway
  • Selenium Pathway
  • Type II interferon signaling (IFNG)
  • Vitamin B12 Metabolism
Pathway Interaction Database
  • Beta2 integrin cell surface interactions
  • Glucocorticoid receptor regulatory network
  • Thromboxane A2 receptor signaling
  • amb2 Integrin signaling
Reactome
  • Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
  • Integrin cell surface interactions
  • Interferon gamma signaling
Pathway Studio
  • Cell Death Mediated by Cytotoxic Cells
  • ICAM1 → AP-1/CREB/ELK-SRF signaling
  • Leukocyte Adhesion to Endothelial Cell
  • MacrophageR → CEBPB/NF-kB signaling
  • Natural Killer Cell Activation
  • Natural Killer Cell Activation through Integrins and non-ITAM-Containing Receptors
  • Nociception-related CCR1 expression targets
  • Nociception-related IL1B expression targets
  • Summarized nociception-related expression targets

Intercellular adhesion molecule 5 (sICAM-5)

Target (abbrv.) sICAM-5
Target (full name) Intercellular adhesion molecule 5
Somalogic ID (Sequence ID) SL005169 (5124-69_3)
Entrez Gene Symbol ICAM5
UniProt ID Q9UMF0
UniProt Comment
  • ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2).

All locus annotations are based on the sentinel SNP (rs5498) and 10 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
  • ICAM1 intercellular adhesion molecule 1
  • CTD-2369P2.5
  • CTD-2369P2.8
  • ICAM4 intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)
  • ICAM5 intercellular adhesion molecule 5, telencephalin
Potentially regulated genes
  • ICAM4 intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)
  • ZGLP1 zinc finger, GATA-like protein 1
  • TYK2 tyrosine kinase 2
  • TYK2
  • KRI1 KRI1 homolog (S. cerevisiae)
  • PPAN peter pan homolog (Drosophila)
  • P2RY11 purinergic receptor P2Y, G-protein coupled, 11
eQTL genes
  • ICAM5 intercellular adhesion molecule 5, telencephalin
  • ICAM4 intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)

 

Results from other genome-wide association studies

Trait P Study Source
Soluble intercellular adhesion molecule 1 (ICAM-1) 5×10-249 21533024 (PMID) GRASP2 nonQTL
Soluble ICAM-1 6×10-89 21533024 (PMID) GWAS Catalog via SNiPA
Plasma soluble intercellular adhesion molecule 1 (ICAM-1) (females) 4.8×10-25 18604267 (PMID) GRASP2 nonQTL
Soluble levels of adhesion molecules 4×10-23 20167578 (PMID) GWAS Catalog via SNiPA
Gene expression of ICAM4 in blood 1.4×10-13 21829388 (PMID) GRASP2 eQTL
ICAM1 gene expression in subcutaneous adipose tissue 4.2×10-10 21602305 (PMID) GRASP2 eQTL
cg05877768 (chr10:34427100) 2.1×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
ICAM1 gene expression in omental adipose tissue 2.1×10-6 21602305 (PMID) GRASP2 eQTL
cg07976603 (chr19:10444482) 3.9×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
ICAM4 gene expression in omental adipose tissue 4.4×10-6 21602305 (PMID) GRASP2 eQTL
cg19431272 (chr19:10625453) 8.4×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
ICAM5 gene expression in omental adipose tissue 3.3×10-5 21602305 (PMID) GRASP2 eQTL

Extends sICAM-1 GWAS to anti-correlation with ICAM5.

SNP rs5498 replicates a published cis-association with sICAM-1 levels GWAS [PubMed] – in this study this SNP also associates in cis with sICAM-5 levels, but displays an opposite effect.

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.