CausalSentinel

Protein Dossier — CBR1 (Carbonyl reductase [NADPH] 1)

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
Fractured bone site(s): Wrist -0.233 0.0662 4.39e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: M23 Internal derangement of knee 0.115 0.0439 0.00855 Wald ratio 1 cis NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis -0.194 0.0773 0.0121 Wald ratio 1 cis NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone -0.232 0.106 0.0278 Wald ratio 1 cis NA
Sleep duration -0.0124 0.0057 0.0293 Wald ratio 1 cis NA
Primary sclerosing cholangitis -0.18 0.0848 0.0334 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0261 0.0123 0.034 Wald ratio 1 cis NA
Weight -0.0133 0.00645 0.0394 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine -0.116 0.058 0.0451 Wald ratio 1 cis NA
Nucleus accumbens volume 6.63 3.4 0.0514 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.0818 0.0437 0.061 Wald ratio 1 cis NA
Diagnoses - main ICD10: R07 Pain in throat and chest 0.0563 0.0308 0.0681 Wald ratio 1 cis NA
…and 63 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

3 association rows across 3 traits (2 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
Height 7e-24 rs2835266 1 GCST90245848 no MR -> candidate analysis
C-reactive protein levels 2e-9 rs2156407 1 GCST90029070 no MR -> candidate analysis
Acetone levels 1e-5 rs41540212 1 GCST90492713 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 713 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
mitral valve prolapse 0.309 common-variant locus no MR -> candidate analysis
osteoporosis 0.191 common-variant locus no MR -> candidate analysis
alcohol drinking 0.189 common-variant locus no MR -> candidate analysis
Left bundle branch block 0.188 common-variant locus no MR -> candidate analysis
femoral neck fracture 0.174 common-variant locus no MR -> candidate analysis
facial morphology 0.162 common-variant locus no MR -> candidate analysis
Burkitt lymphoma 0.161 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.156 common-variant locus no MR -> candidate analysis
stomach disorder 0.155 common-variant locus no MR -> candidate analysis
migraine disorder 0.143 common-variant locus no MR -> candidate analysis
bone disorder 0.142 common-variant locus no MR -> candidate analysis
arthropathy 0.129 common-variant locus no MR -> candidate analysis

Of the 12 rows above, 12 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 (Carbonyl reductase [NADPH] 1)
gnomAD constraint pLI=9.4e-05, LOEUF=1.71 — LoF-tolerant
GWAS Catalog 47 unique SNPs / 94 rows
ClinVar 131 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx 4 clinical annotations across 5 drugs

Caveats declared by the tools

Sources

Provenance