Connecting genetic risk to disease endpoints through the human blood plasma proteome
ONLINE SUPPLEMENTARY INFORMATION
Locus annotations
Locus 19
Top associations per target
| Target | cis/trans | Study | SNP | SNP location | Maj/min allele | MAF | N | βinv | seinv | Pinv | fclog | Plog | Praw |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IL-18 Ra | cis | Discovery | rs2058622 | 2:102,985,424 | G/A | 0.23 | 997 | 0.995 | 0.040 | 9×10-108 | 1.250 | 2.3×10-93 | 9×10-35 |
| IL-18 Ra | cis | Replication | rs2058623 | 2:102,986,170 | A/G | 0.30 | 337 | 0.594 | 0.054 | 3.6×10-24 | 1.240 | 3.1×10-25 | 1×10-23 |
Regional association plots
Interleukin-18 receptor 1 (IL-18 Ra)
Boxplots and histograms for top associations
Interleukin-18 receptor 1 (IL-18 Ra)
| Target (abbrv.) | IL-18 Ra |
| Target (full name) | Interleukin-18 receptor 1 |
| Somalogic ID (Sequence ID) | SL004152 (3446-7_2) |
| Entrez Gene Symbol | IL18R1 |
| UniProt ID | Q13478 |
| 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 (rs2058622) and 93 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 |
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| Potentially regulated genes |
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| eQTL genes |
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Results from other genome-wide association studies
| Trait | P | Study | Source |
|---|---|---|---|
| cg13897122 (chr2:103039518) | 1.6×10-162 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Gene expression of IL18RAP in blood | 2×10-152 | 21829388 (PMID) | GRASP2 eQTL |
| cg11916609 (chr2:102927512) | 6.9×10-89 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| IL18RAP expression | 7.4×10-87 | 20190752 (PMID) | GRASP2 nonQTL |
| Gene expression of IL18RAP (probeID ILMN_1721762) in whole blood | 5.3×10-66 | 22692066 (PMID) | GRASP2 eQTL |
| Serum protein levels (sST2) | 1×10-35 | 23999434 (PMID) | GWAS Catalog via SNiPA |
| Gene expression of IL18R1 (probeID ILMN_1781700) in cerebellum in Alzheimer's disease cases and controls | 7.5×10-24 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL18R1 (probeID ILMN_1781700) in temporal cortex in Alzheimer's disease cases and controls | 2.3×10-20 | 22685416 (PMID) | GRASP2 eQTL |
| Inflammatory bowel disease | 3×10-20 | 23128233 (PMID) | GWAS Catalog via SNiPA |
| Gene expression of IL1RL1 (probeID ILMN_1697444) in temporal cortex in Alzheimer's disease cases and controls | 5×10-19 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_2242900) in temporal cortex in Alzheimer's disease cases and controls | 2.8×10-18 | 22685416 (PMID) | GRASP2 eQTL |
| Atopic dermatitis | 8×10-18 | 23042114 (PMID) | GWAS Catalog via SNiPA |
| Gene expression of IL1RL1 (probeID ILMN_2313672) in temporal cortex in Alzheimer's disease cases and controls | 3.9×10-17 | 22685416 (PMID) | GRASP2 eQTL |
| Celiac disease | 1.2×10-16 | 22057235 (PMID) | GRASP2 nonQTL |
| Gene expression of IL18RAP (probeID ILMN_5130475) in whole blood | 1.5×10-16 | 22692066 (PMID) | GRASP2 eQTL |
| CELIAC DISEASE | 1×10-15 | 20190752 (PMID) | GWAS Catalog via SNiPA |
| Selective immunoglobulin A deficiency (IgAD) | 1.1×10-15 | 20694011 (PMID) | GRASP2 nonQTL |
| Gene expression of IL1RL1 (probeID ILMN_2242900) in cerebellum in Alzheimer's disease cases and controls | 1.7×10-14 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL18R1 (probeID ILMN_1781700) in cerebellum in Alzheimer's disease cases | 2.2×10-14 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_2313672) in cerebellum in Alzheimer's disease cases and controls | 8.1×10-14 | 22685416 (PMID) | GRASP2 eQTL |
| cg16386158 (chr2:102927373) | 3.1×10-13 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Gene expression of IL1RL1 (probeID ILMN_1697444) in temporal cortex in non-Alzheimer's disease samples | 1.5×10-12 | 22685416 (PMID) | GRASP2 eQTL |
| Crohn's disease | 1.6×10-12 | 21297633 (PMID) | GRASP2 nonQTL |
| Crohn's disease (time to surgery) | 2×10-12 | 21102463 (PMID) | GWAS Catalog via SNiPA |
| Gene expression of IL18R1 (probeID ILMN_1781700) in temporal cortex in non-Alzheimer's disease samples | 1.3×10-10 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL18R1 (probeID ILMN_1781700) in cerebellum in non-Alzheimer's disease samples | 2.2×10-10 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_2242900) in temporal cortex in Alzheimer's disease cases | 5.8×10-10 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL18R1 (probeID ILMN_1781700) in temporal cortex in Alzheimer's disease cases | 7.1×10-10 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_2242900) in cerebellum in Alzheimer's disease cases | 7.8×10-10 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_2313672) in temporal cortex in Alzheimer's disease cases | 2.4×10-9 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_2313672) in cerebellum in Alzheimer's disease cases | 5.3×10-9 | 22685416 (PMID) | GRASP2 eQTL |
| Atopic dermatitis with bronchial asthma | 7×10-9 | 23042114 (PMID) | GRASP2 nonQTL |
| Gene expression of IL1RL1 (probeID ILMN_2242900) in temporal cortex in non-Alzheimer's disease samples | 3.6×10-8 | 22685416 (PMID) | GRASP2 eQTL |
| Celiac disease and Crohn's disease | 8.4×10-8 | 21298027 (PMID) | GRASP2 nonQTL |
| Gene expression of IL1RL1 (probeID ILMN_2313672) in temporal cortex in non-Alzheimer's disease samples | 1.1×10-7 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_1697444) in temporal cortex in Alzheimer's disease cases | 1.3×10-7 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_1697444) in cerebellum in Alzheimer's disease cases and controls | 8.4×10-7 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL18RAP [probeset 207072_at] in sputum | 4×10-6 | 21949713 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_2242900) in cerebellum in non-Alzheimer's disease samples | 8×10-6 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_2313672) in cerebellum in non-Alzheimer's disease samples | 8.1×10-6 | 22685416 (PMID) | GRASP2 eQTL |
| Q13478 protein abundance levels | 8.3×10-6 | 22595970 (PMID) | GRASP2 pQTL |
| Gene expression of IL18RAP in blood cells in Celiac disease | 1.5×10-5 | 19128478 (PMID) | GRASP2 eQTL |
| Gene expression of IL18RAP | 1.7×10-5 | 18311140 (PMID) | GRASP2 nonQTL |
| Ulcerative collitis | 1.7×10-5 | Supplemental file | |
| Irritible bowel syndrome | 2.1×10-5 | 18587394 (PMID) | GRASP2 nonQTL |
| Gene expression of IL18R1 (probeID ILMN_1781700) in temporal cortex in Progressive Supranuclear Palsy cases | 4×10-5 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of IL18R1 in blood | 6×10-5 | 21829388 (PMID) | GRASP2 eQTL |
| Gene expression of IL18R1 (probeID ILMN_1781700) in cerebellum in Progressive Supranuclear Palsy cases | 7×10-5 | 22685416 (PMID) | GRASP2 eQTL |
| Serum ratio of (1,6-anhydroglucose)/(deoxycholate) | 1.3×10-4 | 21886157 (PMID) | GRASP2 metabQTL |
| Gene expression of EIF2B5 in normal prepouch ileum | 1.4×10-4 | 23474282 (PMID) | GRASP2 eQTL |
| Gene expression of IL1RL1 (probeID ILMN_2242900) in temporal cortex in Progressive Supranuclear Palsy cases | 1.7×10-4 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of SNX19 in normal prepouch ileum | 4.8×10-4 | 23474282 (PMID) | GRASP2 eQTL |
New insight into the Interleukin-1 receptor cluster.
This locus harbours a replicated cis-association with Interleukin-18 receptor 1 (IL18R1). Andiappan et al. [PubMed] reported this variant as a strong eQTL that affects leprosy and Crohn's disease in opposite directions. The authors argue that polymorphic regulation of human neutrophils can impact beneficial as well as pathological inflammatory responses. This locus also associates with IL1RL1 (the gene coding for sST2) [PubMed] (see Locus 44) and with atopic dermatitis, Crohn's disease (time to surgery), celiac disease, Inflammatory bowel disease.
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.