CausalSentinel

Protein Dossier — ANGPTL1 (Angiopoietin-related protein 1)

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
HDL cholesterol 0.0409 0.0116 4.32e-04 Wald ratio 1 cis NA
Myocardial infarction -0.0847 0.0244 5.30e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma 0.048 0.0157 0.00217 Wald ratio 1 cis NA
Height -0.0209 0.00697 0.0027 Wald ratio 1 cis NA
Coronary heart disease -0.0652 0.0221 0.00321 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0129 0.00481 0.00714 Wald ratio 1 cis NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.109 0.0411 0.00781 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina -0.0875 0.0359 0.0149 Wald ratio 1 cis NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.45 0.185 0.0151 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol -0.0393 0.0165 0.0171 Wald ratio 1 cis NA
High grade serous ovarian cancer 0.0877 0.0381 0.0215 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine 0.0722 0.0315 0.0221 Wald ratio 1 cis NA
…and 105 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

3 association rows across 3 traits (3 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
Angiopoietin-related protein 1 levels 2e-100 rs148080321 1 GCST90246507 no MR -> candidate analysis
Brain shape (segment 40) 4e-16 rs28372846 1 GCST90012919 no MR -> candidate analysis
FEV1 5e-11 rs3753535 1 GCST90270081 MR: beta=0.00954, p=0.0601 (cis)

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

Top diseases by Open Targets association (of 488 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
gastritis 0.47 common-variant locus no MR -> candidate analysis
gestational diabetes 0.427 common-variant locus no MR -> candidate analysis
Hallux valgus 0.425 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 3 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=4.2e-10, LOEUF=1.02 — LoF-tolerant
GWAS Catalog 37 unique SNPs / 74 rows
ClinVar 120 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance