CausalSentinel

Protein Dossier — EGF (Pro-epidermal growth factor)

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
Platelet count -7.6 1.68 5.93e-06 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0441 0.0124 3.83e-04 Wald ratio 1 cis NA
Mean cell volume -0.329 0.106 0.00182 Wald ratio 1 cis NA
Schizophrenia -0.133 0.043 0.0019 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.0869 0.0351 0.0134 Wald ratio 1 cis NA
Height 0.0286 0.0117 0.0142 Wald ratio 1 cis NA
Neo-neuroticism -0.922 0.379 0.0151 Wald ratio 1 cis NA
Mean cell haemoglobin -0.0953 0.0411 0.0203 Wald ratio 1 cis NA
Red blood cell count 0.0203 0.00904 0.0244 Wald ratio 1 cis NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate -0.4 0.183 0.0287 Wald ratio 1 cis NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0641 0.0298 0.0314 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0162 0.00787 0.04 Wald ratio 1 cis NA
…and 112 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

182 association rows across 99 traits (168 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
CLEC1B/EGF protein level ratio 6e-375 rs4444903 1 GCST90314089 no MR -> candidate analysis
EGF/MPIG6B protein level ratio 5e-348 rs4444903 1 GCST90314611 no MR -> candidate analysis
EGF/GP6 protein level ratio 1e-336 rs4444903 1 GCST90314608 no MR -> candidate analysis
CD40LG/EGF protein level ratio 3e-289 rs4444903 1 GCST90313819 no MR -> candidate analysis
Platelet count 6e-283 rs11098063 18 GCST90662907 MR: beta=-7.6, p=5.93e-06 (cis)
EGF/PPIB protein level ratio 2e-272 rs4444903 1 GCST90314612 no MR -> candidate analysis
EGF/MGLL protein level ratio 2e-239 rs4444903 1 GCST90314610 no MR -> candidate analysis
ANGPT1/EGF protein level ratio 6e-205 rs4444903 1 GCST90313264 no MR -> candidate analysis
CRKL/EGF protein level ratio 3e-202 rs4444903 1 GCST90314265 no MR -> candidate analysis
EGF/MANF protein level ratio 3e-195 rs4444903 1 GCST90314609 no MR -> candidate analysis
APP/EGF protein level ratio 4e-192 rs4444903 1 GCST90313322 no MR -> candidate analysis
EGF/TNFSF14 protein level ratio 2e-152 rs4444903 1 GCST90314615 no MR -> candidate analysis
…and 87 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 1538 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
familial primary hypomagnesemia with normocalciuria and normocalcemia 0.679 established (curated) no MR -> candidate analysis
atrial fibrillation 0.63 common-variant locus no MR -> candidate analysis
osteonecrosis 0.548 common-variant locus no MR -> candidate analysis
duodenitis 0.362 common-variant locus no MR -> candidate analysis
Thrombocytopenia 0.246 common-variant locus no MR -> candidate analysis
cholangiocarcinoma 0.182 established (curated) no MR -> candidate analysis
hereditary renal cell carcinoma 0.182 established (curated) no MR -> candidate analysis

Of the 7 rows above, 7 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 0 known modulators (Pro-epidermal growth factor)
gnomAD constraint pLI=1.8e-20, LOEUF=0.784 — LoF-tolerant
GWAS Catalog 101 unique SNPs / 206 rows
ClinVar 684 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance