CausalSentinel

Protein Dossier — ACHE (Acetylcholinesterase)

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
Pulse rate 0.0856 0.0143 2.12e-09 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0438 0.00829 1.31e-07 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated -0.0416 0.0105 7.24e-05 Wald ratio 1 cis NA
Height 0.037 0.00976 1.49e-04 Wald ratio 1 cis NA
Total cholesterol 0.0579 0.0172 7.45e-04 Wald ratio 1 cis NA
Cough on most days -0.159 0.0487 0.00106 Wald ratio 1 cis NA
Transferrin 0.1 0.034 0.00317 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0196 0.00665 0.00327 Wald ratio 1 cis NA
Ulcerative colitis 0.119 0.0418 0.00426 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.108 0.038 0.00463 Wald ratio 1 cis NA
Transferrin Saturation -0.0923 0.0333 0.00565 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema -0.109 0.0402 0.00662 Wald ratio 1 cis NA
…and 115 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

41 association rows across 22 traits (39 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
ACHE protein levels 2e-174 rs145798043 1 GCST90468199 no MR -> candidate analysis
Pulse rate (UKB data field 102) 1e-96 rs13226864 1 GCST90468177 no MR -> candidate analysis
Resting heart rate 1e-41 rs17881696 2 GCST003818 no MR -> candidate analysis
Heart rate 8e-27 rs13245899 1 GCST001969 no MR -> candidate analysis
Heart rate response to recovery post exercise (10 sec) 6e-21 rs17883557 1 GCST005846 no MR -> candidate analysis
Heart rate increase in response to exercise 3e-16 rs76181418 1 GCST005845 no MR -> candidate analysis
Red blood cell count 5e-16 rs538605220 1 GCST007069 no MR -> candidate analysis
Body mass index 1e-15 rs1799805 2 GCST90255621 MR: beta=-0.0142, p=0.0793 (cis)
Red blood cell erythrocyte count (UKB data field 30010) 1e-13 rs538605220 1 GCST90468098 no MR -> candidate analysis
PILRB protein levels 6e-13 rs117954600 1 GCST90470237 no MR -> candidate analysis
Heel bone mineral density 3e-12 rs3847063 1 GCST006979 MR: beta=-0.0416, p=7.24e-05 (cis)
Free Cholesterol to Total Lipids in Medium HDL percentage 1e-11 rs76181418 1 GCST90501187 no MR -> candidate analysis
…and 10 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 2712 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 skeletal system 0.785 common-variant locus no MR -> candidate analysis
skin cancer 0.572 common-variant locus no MR -> candidate analysis
hair color 0.488 common-variant locus no MR -> candidate analysis

Of the 3 rows above, 3 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 20 known modulators (Acetylcholinesterase)
gnomAD constraint pLI=0.95, LOEUF=0.518 — LoF-INTOLERANT
GWAS Catalog 102 unique SNPs / 228 rows
ClinVar 100 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance