CausalSentinel

Protein Dossier — APOH (Beta-2-glycoprotein 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
Height -0.0417 0.012 4.92e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis -0.555 0.202 0.00611 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.0219 0.00822 0.00779 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.192 0.0747 0.0101 Wald ratio 1 cis NA
Fractured bone site(s): Wrist 0.146 0.0589 0.0132 Wald ratio 1 cis NA
Bipolar disorder 0.233 0.0973 0.0167 Wald ratio 1 cis NA
Cigarettes smoked per day 0.787 0.332 0.0178 Wald ratio 1 cis NA
Myocardial infarction 0.0954 0.0406 0.0187 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0177 0.00779 0.0234 Wald ratio 1 cis NA
Body mass index (BMI) 0.0213 0.00951 0.0253 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.02 0.00974 0.0405 Wald ratio 1 cis NA
Eye problems or disorders: Diabetes related eye disease 0.205 0.101 0.042 Wald ratio 1 cis NA
…and 83 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

886 association rows across 609 traits (871 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
Metastasis-suppressor KiSS-1 levels 3e-1155 rs1801690 1 GCST90248203 no MR -> candidate analysis
ATP-dependent RNA helicase DHX8 levels 1e-819 rs7212477 2 GCST90247282 no MR -> candidate analysis
Blood protein levels 7e-431 rs1801690 9 GCST006585 no MR -> candidate analysis
Beta-2-glycoprotein 1 levels 1e-423 rs1801689 2 GCST90246626 no MR -> candidate analysis
Circulating LTBP3 levels 3e-382 rs8178824 1 GCST90860758 no MR -> candidate analysis
V-set and immunoglobulin domain-containing protein 2 levels 2e-270 rs1801690 1 GCST90250193 no MR -> candidate analysis
IL18R1 protein levels 1e-251 rs1801689 1 GCST90469565 no MR -> candidate analysis
TXNDC15 protein levels 6e-239 rs1801689 1 GCST90470990 no MR -> candidate analysis
PRSS53 protein levels 1e-233 rs1801689 1 GCST90470344 no MR -> candidate analysis
ATP-dependent RNA helicase DHX8 levels (DHX8.11601.26.3) 2e-232 rs8178854 2 GCST90240355 no MR -> candidate analysis
APOH protein levels 6e-229 rs118088174 7 GCST90468340 no MR -> candidate analysis
Circulating IL18R1 levels 6e-222 rs8178824 1 GCST90859873 no MR -> candidate analysis
…and 597 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 523 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
atrial fibrillation 0.903 common-variant locus no MR -> candidate analysis
Hypercholesterolemia 0.813 common-variant locus MR: beta=0.0127, p=0.369 (cis)
metabolic syndrome 0.787 common-variant locus no MR -> candidate analysis
familial lipoprotein lipase deficiency 0.749 common-variant locus no MR -> candidate analysis
atrial flutter 0.644 common-variant locus no MR -> candidate analysis
alcohol drinking 0.603 common-variant locus no MR -> candidate analysis
response to statin 0.589 common-variant locus no MR -> candidate analysis
ovarian endometriosis 0.523 common-variant locus no MR -> candidate analysis
chronic obstructive pulmonary disease 0.507 common-variant locus no MR -> candidate analysis
cardiac arrhythmia 0.507 common-variant locus no MR -> candidate analysis
lung abscess 0.461 common-variant locus no MR -> candidate analysis
bronchopneumonia 0.461 common-variant locus no MR -> candidate analysis
nonischemic cardiomyopathy 0.303 common-variant locus no MR -> candidate analysis
heart failure 0.292 common-variant locus no MR -> candidate analysis
stroke disorder 0.045 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=1.4e-19, LOEUF=1.54 — LoF-tolerant
GWAS Catalog 108 unique SNPs / 221 rows
ClinVar 58 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance