CausalSentinel

Protein Dossier — CROT (Peroxisomal carnitine O-octanoyltransferase)

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
Bipolar disorder -0.521 0.126 3.53e-05 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression 0.132 0.0493 0.00756 Wald ratio 1 cis NA
Years of schooling 0.046 0.0172 0.00766 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine 0.162 0.0672 0.0159 Wald ratio 1 cis NA
Major depressive disorder -0.261 0.117 0.0261 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.164 0.0752 0.029 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bone disorder 0.427 0.199 0.0317 Wald ratio 1 cis NA
Height -0.0345 0.0161 0.0321 Wald ratio 1 cis NA
Eye problems or disorders: Diabetes related eye disease 0.279 0.135 0.0389 Wald ratio 1 cis NA
PGC cross-disorder traits -0.135 0.0667 0.0433 Wald ratio 1 cis NA
Putamen volume -64.8 32.9 0.0486 Wald ratio 1 cis NA
Multiple sclerosis -0.178 0.0909 0.0498 Wald ratio 1 cis NA
…and 92 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

14 association rows across 12 traits (11 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 8e-40 rs2051950 1 GCST90245848 MR: beta=-0.0345, p=0.0321 (cis)
ADAM22 protein levels 2e-28 rs79797038 1 GCST90468218 no MR -> candidate analysis
Serum levels of protein CROT 5e-24 rs7776867 1 GCST90087661 no MR -> candidate analysis
Chronic elevation of alanine aminotransferase (cALT) levels 4e-21 rs115038698 2 GCST90129601 no MR -> candidate analysis
Aspartate aminotransferase (AST, mean, inv-norm transformed) 2e-18 rs147423000 1 GCST90479510 no MR -> candidate analysis
Aspartate aminotransferase (AST, minimum, inv-norm transform 4e-14 rs144656711 2 GCST90479511 no MR -> candidate analysis
Blood protein levels 2e-13 rs77463367 1 GCST006585 no MR -> candidate analysis
Peroxisomal carnitine O-octanoyltransferase levels 1e-11 rs117788595 1 GCST90422349 no MR -> candidate analysis
Aspartate aminotransferase levels 1e-10 rs28860289 1 GCST90244010 no MR -> candidate analysis
Lung cancer 1e-6 rs148791337 1 GCST004748 no MR -> candidate analysis
interferon-related traits 4e-6 rs77270176 1 GCST012156 no MR -> candidate analysis
TRAIL levels 7e-6 rs181732910 1 GCST004424 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 92 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
Abnormality of the liver 0.452 common-variant locus no MR -> candidate analysis
hidradenitis 0.421 common-variant locus no MR -> candidate analysis
preeclampsia 0.421 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.419 common-variant locus no MR -> candidate analysis
Intrahepatic cholestasis of pregnancy 0.395 common-variant locus no MR -> candidate analysis
cholestasis, intrahepatic, of pregnancy 3 0.227 common-variant locus no MR -> candidate analysis
gastrointestinal disease 0.166 common-variant locus no MR -> candidate analysis
cholelithiasis 0.132 common-variant locus MR: beta=0.0883, p=0.313 (cis)
Cholecystitis 0.121 common-variant locus no MR -> candidate analysis
lagophthalmos 0.043 common-variant locus no MR -> candidate analysis
systemic lupus erythematosus 0.033 common-variant locus no MR -> candidate analysis

Of the 11 rows above, 10 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 (Peroxisomal carnitine O-octanoyltransferase)
gnomAD constraint pLI=2.9e-27, LOEUF=1.13 — LoF-tolerant
GWAS Catalog 71 unique SNPs / 142 rows
ClinVar 137 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance