CausalSentinel

Protein Dossier — BGLAP (Osteocalcin)

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
Pulse rate -0.0637 0.0211 0.00252 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension 0.0513 0.0194 0.00812 Wald ratio 1 trans NA
Paget’s disease -0.676 0.29 0.0196 Wald ratio 1 trans NA
Urinary albumin-to-creatinine ratio 0.0673 0.0288 0.0196 Wald ratio 1 trans NA
Thalamus volume 68.4 30.5 0.0248 Wald ratio 1 trans NA
Cancer code self-reported: basal cell carcinoma 0.222 0.101 0.0282 Wald ratio 1 trans NA
Years of schooling -0.0385 0.0192 0.0455 Wald ratio 1 trans NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) -0.211 0.106 0.0465 Wald ratio 1 trans NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.662 0.333 0.0465 Wald ratio 1 trans NA
Ferritin -0.0899 0.0462 0.0514 Wald ratio 1 trans NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt -0.403 0.209 0.0538 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoarthritis 0.0689 0.0374 0.0651 Wald ratio 1 trans 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

65 association rows across 51 traits (51 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
Mosaic loss of chromosome Y (Y chromosome dosage) 3e-88 rs2842873 3 GCST009067 no MR -> candidate analysis
Neutrophil count 5e-70 rs3768276 1 GCST90101731 no MR -> candidate analysis
White blood cell count 3e-55 rs3768276 1 GCST90101726 no MR -> candidate analysis
Height 2e-33 rs2758603 1 GCST90245848 no MR -> candidate analysis
Myeloproliferative neoplasms (MTAG) 3e-24 rs1052053 1 GCST90428574 no MR -> candidate analysis
Estimated glomerular filtration rate (cystatin c) 9e-24 rs1052053 1 GCST90428448 no MR -> candidate analysis
Estimated glomerular filtration rate (creatinine, cystatin c 1e-23 rs1052053 1 GCST90428446 no MR -> candidate analysis
Clear cell renal cell carcinoma 2e-19 rs2251636 1 GCST90320055 no MR -> candidate analysis
Serum creatinine levels 1e-16 rs2842870 2 GCST90018979 no MR -> candidate analysis
Estimated glomerular filtration rate (creatinine) 2e-16 rs2842870 2 GCST90100220 no MR -> candidate analysis
Average diameter for VLDL particles 4e-15 rs10908491 1 GCST90501292 no MR -> candidate analysis
estimated glomerular filtration rate (eGFR, minimum, inv-nor 5e-15 rs2842873 1 GCST90479600 no MR -> candidate analysis
…and 39 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 835 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
kidney failure 0.523 common-variant locus no MR -> candidate analysis
thyroid gland carcinoma 0.485 common-variant locus no MR -> candidate analysis
renal carcinoma 0.446 common-variant locus no MR -> candidate analysis
clear cell renal carcinoma 0.424 common-variant locus no MR -> candidate analysis
ischemic stroke 0.414 common-variant locus MR: beta=-0.0933, p=0.24 (trans)
type 2 diabetes mellitus 0.229 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.207 common-variant locus no MR -> candidate analysis
stroke disorder 0.211 common-variant locus no MR -> candidate analysis
intracerebral hemorrhage 0.217 common-variant locus no MR -> candidate analysis
cancer 0.161 common-variant locus MR: beta=0.0513, p=0.00812 (trans)
hypertensive disorder 0.162 common-variant locus no MR -> candidate analysis
small vessel stroke 0.164 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.08 common-variant locus no MR -> candidate analysis
myeloproliferative disorder 0.154 common-variant locus no MR -> candidate analysis
testicular germ cell tumor 0.134 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 13 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=2.6e-06, LOEUF=1.68 — LoF-tolerant
GWAS Catalog 103 unique SNPs / 210 rows
ClinVar 50 records; 8 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance