Connecting genetic risk to disease endpoints through the human blood plasma proteome
ONLINE SUPPLEMENTARY INFORMATION
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
Interleukin-23 receptor (IL-23 R)
Boxplots and histograms for top associations
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 |
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| Pathway Interaction Database |
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| Pathway Studio |
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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.