CausalSentinel

Protein Dossier — BCHE (Cholinesterase)

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
LDL cholesterol 0.0987 0.0237 3.15e-05 Wald ratio 1 trans NA
Total cholesterol 0.0904 0.0231 8.98e-05 Wald ratio 1 trans NA
Triglycerides 0.075 0.0212 3.92e-04 Wald ratio 1 trans NA
Ischemic stroke -0.339 0.106 0.00135 Wald ratio 1 trans NA
Anorexia nervosa -0.56 0.175 0.00137 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis -0.00297 0.00108 0.00587 Inverse variance weighted 2 trans NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis -0.00297 0.00108 0.00587 Inverse variance weighted 2 trans NA
Sleep duration -0.0261 0.00958 0.00651 Inverse variance weighted 2 trans NA
Sleep duration -0.0261 0.00958 0.00651 Inverse variance weighted 2 trans NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.00377 0.00144 0.00884 Inverse variance weighted 2 trans NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.00377 0.00144 0.00884 Inverse variance weighted 2 trans NA
Serum cystatin C (eGFRcys) -0.0301 0.0115 0.00902 Wald ratio 1 trans NA
…and 158 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

355 association rows across 340 traits (349 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
Butyrylcholinesterase levels 6e-262 rs1803274 1 GCST001207 no MR -> candidate analysis
Cholinesterase levels 1e-251 rs2668196 1 GCST90247015 no MR -> candidate analysis
BCHE protein levels 2e-170 rs115790699 5 GCST90468429 no MR -> candidate analysis
Cardiovascular disease risk factors 6e-92 rs1803274 1 GCST001247 no MR -> candidate analysis
Platelet-activating factor acetylhydrolase levels 9e-76 rs1799807 1 GCST90248843 no MR -> candidate analysis
Integral membrane protein 2B levels 3e-72 rs78119247 2 GCST90248138 no MR -> candidate analysis
Peflin levels 1e-69 rs1799807 2 GCST90248940 no MR -> candidate analysis
Carnitine O-palmitoyltransferase 1, muscle isoform levels 4e-67 rs2668196 1 GCST90247142 no MR -> candidate analysis
Short-chain specific acyl-CoA dehydrogenase, mitochondrial l 1e-53 rs71674639 2 GCST90249434 no MR -> candidate analysis
Serum levels of protein PMEPA1 9e-53 rs2668206 1 GCST90089581 no MR -> candidate analysis
Galactosylceramide sulfotransferase levels 6e-52 rs71674639 1 GCST90247681 no MR -> candidate analysis
Interleukin-36 receptor antagonist protein levels 6e-52 rs71674639 1 GCST90248072 no MR -> candidate analysis
…and 328 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 940 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
butyrylcholinesterase deficiency 0.945 established (curated) no MR -> candidate analysis
mathematical ability 0.561 common-variant locus no MR -> candidate analysis
adverse effect 0.495 common-variant locus no MR -> candidate analysis
response to stimulus 0.495 common-variant locus no MR -> candidate analysis
pneumococcal pneumonia 0.492 common-variant locus no MR -> candidate analysis
auditory system disorder 0.448 common-variant locus no MR -> candidate analysis
Abnormality of the genital system 0.419 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.396 common-variant locus no MR -> candidate analysis
male infertility 0.346 common-variant locus no MR -> candidate analysis
hypotensive disorder 0.346 common-variant locus no MR -> candidate analysis
hereditary disease 0.317 established (curated) no MR -> candidate analysis
Abnormality of the gastrointestinal tract 0.272 common-variant locus no MR -> candidate analysis
placental abruption 0.261 common-variant locus no MR -> candidate analysis
placenta praevia 0.261 common-variant locus no MR -> candidate analysis
colon carcinoma 0.261 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 1 known modulators (Cholinesterase)
gnomAD constraint pLI=7.6e-16, LOEUF=1.19 — LoF-tolerant
GWAS Catalog 110 unique SNPs / 197 rows
ClinVar 258 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx 14 clinical annotations across 4 drugs

Caveats declared by the tools

Sources

Provenance