CausalSentinel

Protein Dossier — PDGFRA (Platelet-derived growth factor receptor alpha)

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
Diagnoses - main ICD10: I83 Varicose veins of lower extremities 0.118 0.0284 3.22e-05 Wald ratio 1 trans NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] 0.0954 0.0346 0.00584 Wald ratio 1 trans NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.0728 0.0301 0.0158 Wald ratio 1 trans NA
Diagnoses - main ICD10: N81 Female genital prolapse 0.0822 0.0352 0.0195 Wald ratio 1 trans NA
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.313 0.142 0.0278 Wald ratio 1 trans NA
Creatinine (enzymatic) in urine 0.00925 0.00438 0.0345 Wald ratio 1 trans NA
Diagnoses - main ICD10: R55 Syncope and collapse -0.111 0.0543 0.041 Wald ratio 1 trans NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine -0.0703 0.0345 0.0416 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoporosis 0.0689 0.0343 0.0444 Wald ratio 1 trans NA
Diastolic blood pressure automated reading 0.00941 0.0047 0.0454 Wald ratio 1 trans NA
Fracture resulting from simple fall 0.023 0.0117 0.0504 Wald ratio 1 trans NA
Coronary heart disease 0.0481 0.0251 0.0558 Wald ratio 1 trans NA
…and 57 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

56 association rows across 35 traits (52 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
Circulating PDGFRA levels 2e-450 rs35597368 3 GCST90859718 no MR -> candidate analysis
IL6ST/PDGFRA protein level ratio 3e-441 rs35597368 1 GCST90315169 no MR -> candidate analysis
Bone mineral density mean 1e-300 rs140863234 2 GCST90321120 no MR -> candidate analysis
Corneal curvature 2e-73 rs1800813 7 GCST90012795 no MR -> candidate analysis
PDGFRA protein levels 9e-58 rs139236922 3 GCST90470191 no MR -> candidate analysis
Height 1e-36 rs6554162 1 GCST90245848 no MR -> candidate analysis
Pulse pressure 1e-22 rs6554163 2 GCST90310296 no MR -> candidate analysis
Platelet-derived growth factor receptor alpha levels 2e-21 rs10028020 2 GCST90060028 no MR -> candidate analysis
Aortic stenosis 2e-20 rs4864857 3 GCST90837544 no MR -> candidate analysis
Core binding factor acute myeloid leukemia 3e-18 rs890206; rs1559715; rs17084040; rs718454; rs12506783; rs7678144 2 GCST008413 no MR -> candidate analysis
Mean corpuscular volume (UKB data field 30040) 8e-17 rs542853222 1 GCST90468086 no MR -> candidate analysis
Aortic stenosis (MTAG) 2e-16 rs4864861 1 GCST90651070 no MR -> candidate analysis
…and 23 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 4767 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
gastrointestinal stromal tumor 0.647 established (curated) no MR -> candidate analysis
GIST-plus syndrome 0.835 established (curated) no MR -> candidate analysis
ovarian cancer 0.625 established (curated) MR: beta=0.0397, p=0.225 (trans)
Abnormality of the skeletal system 0.786 common-variant locus no MR -> candidate analysis

Of the 4 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 6 known modulators (Platelet-derived growth factor receptor alpha)
gnomAD constraint pLI=1, LOEUF=0.287 — LoF-INTOLERANT
GWAS Catalog 75 unique SNPs / 150 rows
ClinVar 4021 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance