CausalSentinel

Protein Dossier — ASPN (Asporin)

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
Height 0.0508 0.00656 9.79e-15 Wald ratio 1 cis 1.47e-06
Non-cancer illness code self-reported: hypertension 0.0306 0.009 6.77e-04 Wald ratio 1 cis NA
Body mass index (BMI) -0.018 0.00544 9.21e-04 Wald ratio 1 cis NA
Potassium in urine 0.0146 0.00553 0.00806 Wald ratio 1 cis NA
Fasting glucose -0.0165 0.00699 0.0181 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids -0.0869 0.0382 0.023 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma 0.0937 0.0415 0.0239 Wald ratio 1 cis NA
Neuroticism -0.0191 0.00847 0.0244 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0155 0.00704 0.0274 Wald ratio 1 cis NA
PGC cross-disorder traits 0.0571 0.0262 0.0297 Wald ratio 1 cis NA
Diagnoses - main ICD10: M23 Internal derangement of knee -0.0848 0.0399 0.0337 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis -0.0395 0.019 0.0372 Wald ratio 1 cis NA
…and 99 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

13 association rows across 11 traits (12 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
COL6A3/OGN protein level ratio 2e-3781 rs8067 1 GCST90314177 no MR -> candidate analysis
COLEC12/OGN protein level ratio 3e-3306 rs8067 1 GCST90314184 no MR -> candidate analysis
IGFBP4/OGN protein level ratio 1e-2613 rs8067 1 GCST90315134 no MR -> candidate analysis
Circulating GDF2 levels 2e-47 rs200538582 1 GCST90859810 no MR -> candidate analysis
AGRP/CCN1 protein level ratio 2e-36 rs8067 1 GCST90313202 no MR -> candidate analysis
Asporin levels (ASPN.6451.64.3) 2e-20 rs41278695 1 GCST90240347 no MR -> candidate analysis
ASPN protein levels 2e-14 rs182736327 1 GCST90468377 no MR -> candidate analysis
GDF2 protein levels 5e-12 rs113478791 2 GCST90469322 no MR -> candidate analysis
Body mass index 7e-10 rs7033979 1 GCST90018947 MR: beta=-0.018, p=9.21e-04 (cis)
Urate levels 3e-9 rs3174352 2 GCST008972 no MR -> candidate analysis
Height 2e-8 rs13301537 1 GCST90245844 MR: beta=0.0508, p=9.79e-15 (cis)

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

Top diseases by Open Targets association (of 756 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
obstructive sleep apnea syndrome 0.205 common-variant locus no MR -> candidate analysis
skin disorder 0.138 common-variant locus no MR -> candidate analysis
mononeuropathy 0.131 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.11 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 4 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=3.8e-11, LOEUF=1.2 — LoF-tolerant
GWAS Catalog 64 unique SNPs / 126 rows
ClinVar 72 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance