CausalSentinel

Protein Dossier — CST8 (Cystatin-8)

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
Alzheimer’s disease -0.0463 0.0288 0.108 Wald ratio 1 trans NA

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 9 traits (8 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
Cystatin C plasma levels 1e-308 rs2273378 1 GCST90100559 no MR -> candidate analysis
Cystatin C levels 7e-21 rs2983288 4 GCST90019504 no MR -> candidate analysis
CST1 protein levels 5e-20 rs113118940 1 GCST90468893 no MR -> candidate analysis
CST3 protein levels 7e-16 rs112998431 1 GCST90468894 no MR -> candidate analysis
Alzheimer disease and age of onset 1e-8 rs113118940 1 GCST003427 no MR -> candidate analysis
Peripheral arterial disease (traffic-related air pollution i 4e-7 rs2073300 1 GCST004482 no MR -> candidate analysis
S.aureus induced IL-6 level 4e-7 rs6114143 1 GCST90308635 no MR -> candidate analysis
Thrombomodulin levels in ischemic stroke 1e-6 rs238670 1 GCST003234 no MR -> candidate analysis
High-sensitivity cardiac troponin I concentration 1e-6 rs3004116 1 GCST90095177 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 148 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
alcohol drinking 0.447 common-variant locus no MR -> candidate analysis
alopecia areata 0.196 common-variant locus no MR -> candidate analysis

Of the 2 rows above, 2 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=4.1e-10, LOEUF=2.47 — LoF-tolerant
GWAS Catalog 44 unique SNPs / 83 rows
ClinVar 57 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance