CausalSentinel

Protein Dossier — QDPR (Dihydropteridine reductase)

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
Transferrin -0.0722 0.0212 6.54e-04 Wald ratio 1 cis NA
Forearm bone mineral density 0.0872 0.0319 0.00635 Wald ratio 1 cis NA
Ischemic stroke -0.0872 0.0335 0.00932 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0632 0.0243 0.00948 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0197 0.00833 0.0182 Wald ratio 1 cis NA
Sleep duration -0.0082 0.00384 0.0329 Wald ratio 1 cis NA
HOMA-IR -0.0176 0.00847 0.0372 Wald ratio 1 cis NA
Haemoglobin concentration 0.0251 0.0122 0.0396 Wald ratio 1 cis NA
Rheumatoid arthritis -0.0692 0.0346 0.0457 Wald ratio 1 cis NA
Ferritin 0.0383 0.0192 0.0465 Wald ratio 1 cis NA
Clear cell ovarian cancer 0.167 0.0861 0.053 Wald ratio 1 cis NA
Hirschsprung’s disease 0.777 0.406 0.0559 Wald ratio 1 cis NA
…and 91 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

11 association rows across 8 traits (8 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
QDPR protein levels 4e-42 rs200967774 4 GCST90470400 no MR -> candidate analysis
Dihydropteridine reductase levels 3e-33 rs3796809 1 GCST90421397 no MR -> candidate analysis
Circulating QDPR levels 8e-30 rs33912980 1 GCST90860370 no MR -> candidate analysis
8-isoprostaglandin-F2alpha x bisphenol A interaction 4e-9 rs6855040 1 GCST90061013 no MR -> candidate analysis
Regional cortical thickness (lingual) 2e-8 rs3733574 1 GCST90399887 no MR -> candidate analysis
Alzheimer’s disease, proxy Alzheimer’s disease or related de 3e-6 rs147260776 1 GCST90654661 no MR -> candidate analysis
Cognitive performance (language) (longitudinal) 6e-6 rs78903959 1 GCST90270903 no MR -> candidate analysis
Response to platinum-based chemotherapy (carboplatin) 8e-6 rs2518590 1 GCST001204 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 226 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
dihydropteridine reductase deficiency 0.933 established (curated) no MR -> candidate analysis
Hyperphenylalaninemia 0.868 established (curated) no MR -> candidate analysis
6-pyruvoyl-tetrahydropterin synthase deficiency 0.559 established (curated) no MR -> candidate analysis
BH4-deficient hyperphenylalaninemia A 0.559 established (curated) no MR -> candidate analysis
hemoglobin E disease 0.438 established (curated) no MR -> candidate analysis
hyperphenylalaninemia due to tetrahydrobiopterin deficiency 0.438 established (curated) no MR -> candidate analysis
hereditary disease 0.313 established (curated) no MR -> candidate analysis
hearing loss disorder 0.256 common-variant locus no MR -> candidate analysis
arthropathy 0.251 common-variant locus no MR -> candidate analysis
digestive system disorder 0.135 common-variant locus no MR -> candidate analysis
secondary malignant neoplasm 0.131 common-variant locus no MR -> candidate analysis
infectious meningitis 0.115 common-variant locus no MR -> candidate analysis
male reproductive organ cancer 0.115 common-variant locus no MR -> candidate analysis
Anisometropia 0.113 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.11 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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 (Dihydropteridine reductase)
gnomAD constraint pLI=1.9e-06, LOEUF=1.03 — LoF-tolerant
GWAS Catalog 43 unique SNPs / 83 rows
ClinVar 483 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance