HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 49

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
Siglec-9 cis Discovery rs2691273 19:51,596,136 A/G 0.46 993 0.764 0.039 3.1×10-73 4.930 1.3×10-81 1.1×10-89
Siglec-9 cis Replication rs2569428 19:51,608,796 G/A 0.42 337 0.517 0.066 8.1×10-14 3.150 9×10-16 5.2×10-14

 

Regional association plots

Sialic acid-binding Ig-like lectin 9 (Siglec-9)

 

Boxplots and histograms for top associations

Sialic acid-binding Ig-like lectin 9 (Siglec-9)

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

Sialic acid-binding Ig-like lectin 9 (Siglec-9)

Target (abbrv.) Siglec-9
Target (full name) Sialic acid-binding Ig-like lectin 9
Somalogic ID (Sequence ID) SL005219 (3007-7_2)
Entrez Gene Symbol SIGLEC9
UniProt ID Q9Y336
UniProt Comment
  • Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface.
Pathway Studio
  • Natural Killer Cell Inhibitory Receptor Signaling

All locus annotations are based on the sentinel SNP (rs2691273) and 1 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
  • CTU1 cytosolic thiouridylase subunit 1
eQTL genes
  • CTU1 cytosolic thiouridylase subunit 1

 

Results from other genome-wide association studies

No associations available.

An example of a genetically determined epitope effect.

This locus harbours a replicated cis-pQTL with Sialic acid-binding Ig-like lectin 9 (SIGLEC9). SIGLEC9 levels display a strong bimodal distribution that replicates in QMDiab. Imputed data suggests two linked causative SNPs: rs2075803 (K100E) and rs2258983 (A315E) (r2=0.39 with rs2691273). These two variants were experimentally shown not to impact the gene function [PubMed]. rs2075803 (K100E) is located in the carbohydrate recognition domain of SIGLEC9. rs2075803 (K100E) is located in the carbohydrate recognition domain of SIGLEC9 and hence accessible to aptamer binding. Interesting enough, when excluding samples with very low SIGLEC9 levels, a functionally very convincing trans-association with rs10935480 (Locus 52) can be uncovered (p=7.5×10-6). The SIGLEC9 distribution is highly bi-modal, with SIGLEC9 levels of rs2075803-G homozygotes three orders of magnitude lower than those of carriers of the rs2075803-A allele. Interestingly, when excluding samples with low SIGLEC9 levels, a functionally relevant trans-association with rs10935480 (Locus 52) is found (p=7.5×10-6). rs10935480 is a replicated trans-association with Vascular endothelial growth factor receptor 3 (FLT4, aka VEGF sR3). The SNP is located near the ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 6 (ST3GAL6) gene, linking genetic variance at ST3GAL6 with FLT4 and SIGLEC9.


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.