HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 251

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
IL-23 R cis Discovery rs11209026 1:67,705,958 G/A 0.06 996 -0.742 0.089 3.4×10-16 -1.190 1.4×10-13 1.3×10-6
IL-23 R cis Replication rs9988642 1:67,726,104 A/G 0.09 337 -0.001 0.105 0.989 -1.010 0.85 0.767

 

Regional association plots

 

Boxplots and histograms for top associations

Interleukin-23 receptor (IL-23 R)

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

Interleukin-23 receptor (IL-23 R)

Target (abbrv.) IL-23 R
Target (full name) Interleukin-23 receptor
Somalogic ID (Sequence ID) SL005185 (5088-175_3)
Entrez Gene Symbol IL23R
UniProt ID Q5VWK5
UniProt Comment
  • Associates with IL12RB1 to form the interleukin-23 receptor. Binds IL23 and mediates T-cells, NK cells and possibly certain macrophage/myeloid cells stimulation probably through activation of the Jak-Stat signaling cascade. IL23 functions in innate and adaptive immunity and may participate in acute response to infection in peripheral tissues. IL23 may be responsible for autoimmune inflammatory diseases and be important for tumorigenesis.
Pathway Interaction Database
  • IL23-mediated signaling events
Pathway Studio
  • Th17 Cell Differentiation

All locus annotations are based on the sentinel SNP (rs11209026) and 25 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

 

Results from other genome-wide association studies

Trait P Study Source
Inflammatory bowel disease 8×10-161 23128233 (PMID) GWAS Catalog via SNiPA
Crohn's disease 2.2×10-68 18587394 (PMID) GRASP2 nonQTL
Crohn's disease (time to surgery) 1×10-64 21102463 (PMID) GWAS Catalog via SNiPA
Selective immunoglobulin A deficiency (IgAD) 6.7×10-63 20694011 (PMID) GRASP2 nonQTL
Irritible bowel syndrome 1×10-35 18587394 (PMID) GRASP2 nonQTL
Ulcerative colitis 5×10-28 21297633 (PMID) GWAS Catalog via SNiPA
Ulcerative collitis 1.6×10-27 Supplemental file
Psoriasis 1.1×10-26 23143594 (PMID) GRASP2 nonQTL
Psoriasis and Crohn's disease combined 1.8×10-22 22482804 (PMID) GRASP2 nonQTL
Ankylosing spondylitis 2×10-17 21743469 (PMID) GWAS Catalog via SNiPA
Irritable bowel disorder 1×10-15 19915574 (PMID) GRASP2 nonQTL
Inflammatory bowel diseases 4.6×10-11 pha002847 (dbGaP) dbGaP via SNiPA
Pediatric Inflammatory Bowel Disease 7.5×10-11 18758464 (PMID) GRASP2 nonQTL
Pediatric Crohn's disease 3.4×10-10 18758464 (PMID) GRASP2 nonQTL
Ankylosing spondylitis (HLA-B27 positive) 4.5×10-8 21743469 (PMID) GRASP2 nonQTL
let-7d miRNA expression in lymphoblastoid cell lines 4.8×10-6 22658545 (PMID) GRASP2 mirQTL
Gene expression of SKP2 in blood 7.2×10-6 21829388 (PMID) GRASP2 eQTL
miR-20a miRNA expression in lymphoblastoid cell lines 9.6×10-6 22658545 (PMID) GRASP2 mirQTL
Serum ratio of (1,3,7-trimethylurate)/(butyrylcarnitine) 9×10-5 21886157 (PMID) GRASP2 metabQTL
Serum ratio of (2-hydroxyisobutyrate)/(sebacate (decanedioate)) 2.2×10-4 21886157 (PMID) GRASP2 metabQTL
Type 1 diabetes, Rheumatoid arthritis, Crohn's disease, combined case analysis 4.8×10-4 17554300 (PMID) GRASP2 nonQTL

Lower levels of IL23R may be protective for multiple autoimmune disorders, including ankylosing spondylitis.

This locus hosts a non-replicated cis-pQTL with Interleukin-23 receptor (IL23R). Evans et al. [PubMed] show that the minor allele of rs11209026 is strongly protective for ankylosing spondylitis. Here we show that the minor allele of rs11209026 associates with lower levels of blood circulating IL23R protein levels. The minor allele variant of rs11209026 is strongly protective of many other autoimmune disorders, including Crohn's disease, ulcerative colitis and psoriasis. See Locus 11 and Locus 14 for two other associations of ERAP1 in relation to ankylosing spondylitis. Evans et al. [PubMed] discuss the interaction of ERAP1 and IL23R.

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.