CausalSentinel

Protein Dossier — HPGDS (Hematopoietic prostaglandin D synthase)

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
Age at menarche -0.0546 0.0131 3.10e-05 Wald ratio 1 cis NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] 0.139 0.041 7.00e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0292 0.00935 0.00178 Wald ratio 1 cis NA
Birth weight 0.0248 0.00842 0.00322 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter -0.225 0.0849 0.00799 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities 0.0947 0.0359 0.00831 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0144 0.00578 0.0129 Wald ratio 1 cis NA
PGC cross-disorder traits -0.0681 0.0284 0.0166 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bone disorder -0.484 0.206 0.0186 Wald ratio 1 cis NA
Rheumatoid arthritis -0.0892 0.0389 0.0218 Wald ratio 1 cis NA
Diagnoses - main ICD10: R11 Nausea and vomiting 0.173 0.0761 0.0228 Wald ratio 1 cis NA
HDL cholesterol 0.0241 0.0111 0.0305 Wald ratio 1 cis NA
…and 100 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

24 association rows across 16 traits (19 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 HPGDS levels 2e-1121 rs7438414 4 GCST90860315 no MR -> candidate analysis
Hematopoietic prostaglandin D synthase levels 3e-244 rs6532479 2 GCST90247924 no MR -> candidate analysis
Serum levels of protein HPGDS 2e-113 rs72665697 2 GCST90087062 no MR -> candidate analysis
Hematopoietic prostaglandin D synthase levels (HPGDS.12549.3 1e-71 rs1965049 2 GCST90241378 no MR -> candidate analysis
Blood protein levels 4e-59 rs11097414 1 GCST006585 no MR -> candidate analysis
Hematopoietic prostaglandin D synthase level in Chronic kidn 3e-30 rs116304230 1 GCST90233535 no MR -> candidate analysis
Menarche (age at onset) 2e-18 rs7438414 1 GCST007078 no MR -> candidate analysis
QT interval 5e-15 rs10028613 1 GCST90179153 no MR -> candidate analysis
HPGDS protein levels 4e-13 rs9762154 1 GCST90469472 no MR -> candidate analysis
Male puberty timing (age at voice breaking MTAG) 2e-11 rs767657 1 GCST90012088 no MR -> candidate analysis
Testicular germ cell tumor 1e-8 rs17021463 3 GCST002023 no MR -> candidate analysis
Substantia nigra iron levels (quantitative susceptibility ma 2e-8 rs10516950 1 GCST90551871 no MR -> candidate analysis
…and 4 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 957 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
glaucoma 0.618 common-variant locus MR: beta=0.0498, p=0.268 (cis)
open-angle glaucoma 0.576 common-variant locus no MR -> candidate analysis
testicular cancer 0.517 common-variant locus no MR -> candidate analysis
Proptosis 0.517 common-variant locus no MR -> candidate analysis
spinal stenosis 0.504 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.47 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.413 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.081 common-variant locus no MR -> candidate analysis
cancer 0.038 common-variant locus MR: beta=0.0292, p=0.00178 (cis)
prostate cancer 0.069 common-variant locus MR: beta=-0.136, p=0.074 (cis)
alcohol drinking 0.072 common-variant locus no MR -> candidate analysis
stroke disorder 0.072 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 9 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 (Hematopoietic prostaglandin D synthase)
gnomAD constraint pLI=2e-10, LOEUF=1.56 — LoF-tolerant
GWAS Catalog 59 unique SNPs / 118 rows
ClinVar 55 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance