CausalSentinel

Protein Dossier — IL18 (Interleukin-18)

MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).

1. Published MR estimates (retrieved, not computed)

Outcome beta se p method nSNP cis/trans coloc
Type 2 diabetes 0.223 0.0615 2.85e-04 Inverse variance weighted 2 trans NA
Type 2 diabetes 0.223 0.0615 2.85e-04 Inverse variance weighted 2 cis NA
Potassium in urine -0.0239 0.00753 0.00154 Inverse variance weighted 2 trans NA
Potassium in urine -0.0239 0.00753 0.00154 Inverse variance weighted 2 cis NA
Non-cancer illness code self-reported: bone disorder 0.351 0.113 0.00189 Inverse variance weighted 2 trans NA
Non-cancer illness code self-reported: bone disorder 0.351 0.113 0.00189 Inverse variance weighted 2 cis NA
Systemic lupus erythematosus -0.524 0.178 0.00327 Wald ratio 1 cis NA
Sodium in urine -0.0199 0.00731 0.00653 Inverse variance weighted 2 trans NA
Sodium in urine -0.0199 0.00731 0.00653 Inverse variance weighted 2 cis NA
Lung adenocarcinoma -0.235 0.0908 0.00955 Inverse variance weighted 2 trans NA
Lung adenocarcinoma -0.235 0.0908 0.00955 Inverse variance weighted 2 cis NA
2hr glucose -0.183 0.0724 0.0116 Wald ratio 1 cis NA
…and 160 more outcomes (see JSON)              

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

12 association rows across 8 traits (10 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.

Trait best p lead SNP n assoc study MR status  
Interleukin-18 levels 1e-119 rs5744249 5 GCST90012024 no MR -> candidate analysis  
Circulating PTS levels 1e-53 rs111311302 1 GCST90860729 no MR -> candidate analysis  
IL18 protein levels 1e-12 rs5744254 1 GCST90469567 no MR -> candidate analysis  
Age of smoking initiation (MTAG) 4e-10 rs5744250 1 GCST007462 no MR -> candidate analysis  
Smoking initiation (MTAG) 1e-9 rs117695734 1 GCST90296430 no MR -> candidate analysis  
Bone mineral density variability 2e-8 rs143917761 1 GCST90321119 no MR -> candidate analysis  
Trypanosoma cruzi infection 8e-7 rs4937075 1 GCST90026452 no MR -> candidate analysis  
Vaginal microbiome MetaCyc pathway (KDO-NAGLIPASYN-PWY super 1e-6 rs5744233 1 GCST90026751 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 1985 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.

Disease genetic assoc. burden (ExWAS) causal status MR status
smoking initiation 0.211 common-variant locus no MR -> candidate analysis
systemic lupus erythematosus 0.059 common-variant locus MR: beta=-0.524, p=0.00327 (cis)

Of the 2 rows above, 1 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.

5. Downstream annotation (druggability & safety preview)

Layer Result
ChEMBL druggability 3 known modulators (Interleukin-18)
gnomAD constraint pLI=0.031, LOEUF=1.01 — LoF-tolerant
GWAS Catalog 39 unique SNPs / 78 rows
ClinVar 37 records; 9 pathogenic in sample of 30
PharmGKB/ClinPGx 4 clinical annotations across 3 drugs

Caveats declared by the tools

Sources

Provenance