CausalSentinel

Protein Dossier — AOC1 (Diamine oxidase [copper-containing])

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 -0.0235 0.00379 5.40e-10 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0107 0.00259 3.29e-05 Wald ratio 1 cis NA
Weight -0.0104 0.00278 1.87e-04 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.00912 0.00273 8.23e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb 0.0683 0.0224 0.00227 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression 0.0367 0.0125 0.00332 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract -0.118 0.0405 0.00347 Wald ratio 1 cis NA
Diagnoses - main ICD10: R55 Syncope and collapse 0.0818 0.0308 0.00792 Wald ratio 1 cis NA
Small vessel disease 0.122 0.0471 0.00955 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0208 0.0085 0.0144 Wald ratio 1 cis NA
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 0.829 0.35 0.018 Wald ratio 1 cis NA
HDL cholesterol 0.0142 0.00627 0.0232 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

222 association rows across 145 traits (215 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
Amiloride-sensitive amine oxidase [copper-containing] levels 5e-1179 rs10452848 3 GCST90246408 no MR -> candidate analysis
Circulating AOC1 levels 1e-464 rs1049742 1 GCST90860746 no MR -> candidate analysis
Amiloride-sensitive amine oxidase [copper-containing] (analy 2e-404 rs62492368 1 GCST90422692 no MR -> candidate analysis
Height 1e-300 rs6977081 8 GCST90245848 MR: beta=-0.0235, p=5.40e-10 (cis)
Blood protein levels 3e-239 rs10452848 1 GCST006585 no MR -> candidate analysis
X-12688 levels 2e-131 rs59577667 1 GCST90245554 no MR -> candidate analysis
Appendicular lean mass 1e-113 rs6977416 3 GCST90000025 no MR -> candidate analysis
N-acetyl-isoputreanine levels 7e-90 rs62492368 4 GCST90200195 no MR -> candidate analysis
Urine 1-methylhistamine levels in chronic kidney disease 2e-86 rs62492368 1 GCST90264234 no MR -> candidate analysis
Urine X-23656 levels in chronic kidney disease 1e-76 rs6464114 1 GCST90266622 no MR -> candidate analysis
X-24020 levels 2e-72 rs62492368 4 GCST90245737 no MR -> candidate analysis
Serum levels of protein AOC1 1e-60 rs139995291 3 GCST90089296 no MR -> candidate analysis
…and 133 more traits (see JSON)          

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

Top diseases by Open Targets association (of 751 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
Abnormality of the skeletal system 0.76 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.581 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.568 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.479 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.468 common-variant locus no MR -> candidate analysis
carpal tunnel syndrome 0.449 common-variant locus no MR -> candidate analysis
gout 0.434 common-variant locus no MR -> candidate analysis
metabolic syndrome 0.391 common-variant locus no MR -> candidate analysis
metabolic dysfunction-associated steatotic liver disease 0.385 common-variant locus no MR -> candidate analysis
heart disorder 0.319 common-variant locus no MR -> candidate analysis
breast carcinoma 0.279 common-variant locus no MR -> candidate analysis
osteoarthritis, knee 0.23 common-variant locus MR: beta=0.0513, p=0.183 (cis)
total knee arthroplasty 0.187 common-variant locus no MR -> candidate analysis
neuroendocrine neoplasm 0.178 common-variant locus no MR -> candidate analysis
total joint arthroplasty 0.171 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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 1 known modulators (Diamine oxidase [copper-containing])
gnomAD constraint pLI=1.7e-20, LOEUF=1.26 — LoF-tolerant
GWAS Catalog 114 unique SNPs / 244 rows
ClinVar 204 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance