CausalSentinel

Protein Dossier — GGH (Gamma-glutamyl hydrolase)

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
Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level 0.434 0.0999 1.40e-05 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0182 0.00623 0.00351 Wald ratio 1 cis NA
Fracture resulting from simple fall -0.0428 0.0165 0.00965 Wald ratio 1 cis NA
Hip osteoarthritis 0.164 0.07 0.0191 Wald ratio 1 cis NA
Packed cell volume -0.1 0.0428 0.0193 Wald ratio 1 cis NA
Forearm bone mineral density 0.0815 0.0382 0.033 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.118 0.0565 0.0369 Wald ratio 1 cis NA
Mean cell haemoglobin concentration 0.0179 0.00864 0.0382 Wald ratio 1 cis NA
Birth length -0.0485 0.0235 0.0395 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.072 0.0367 0.0497 Wald ratio 1 cis NA
Cancer code self-reported: small intestine or small bowel cancer 0.396 0.203 0.0509 Wald ratio 1 cis NA
Diagnoses - main ICD10: L03 Cellulitis 0.118 0.0604 0.0513 Wald ratio 1 cis NA
…and 87 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

13 association rows across 7 traits (13 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
Gamma-glutamyl hydrolase levels 8e-261 rs12676348 3 GCST90247726 no MR -> candidate analysis
GGH protein levels 5e-226 rs190945668 3 GCST90469335 no MR -> candidate analysis
Serum levels of protein GGH 9e-112 rs3758147 2 GCST90090663 no MR -> candidate analysis
Gamma-glutamyl hydrolase levels (GGH.9370.69.3) 2e-42 rs116323041 1 GCST90241235 no MR -> candidate analysis
Calcium levels 1e-11 rs111291669 2 GCST90018951 no MR -> candidate analysis
Alanine transaminase (ALT, minimum, inv-norm transformed) 2e-11 rs3780129 1 GCST90479508 no MR -> candidate analysis
Hemoglobin concentration 2e-10 rs3780129 1 GCST90002314 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 176 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
Limb pain 0.368 common-variant locus no MR -> candidate analysis
Headache 0.368 common-variant locus no MR -> candidate analysis
Abdominal pain 0.368 common-variant locus no MR -> candidate analysis
alcohol drinking 0.097 common-variant locus no MR -> candidate analysis
urolithiasis 0.097 common-variant locus no MR -> candidate analysis
exostosis 0.097 common-variant locus no MR -> candidate analysis
glomerulonephritis 0.094 common-variant locus no MR -> candidate analysis
dementia 0.071 common-variant locus no MR -> candidate analysis
lung cancer 0.037 established (curated) MR: beta=0.076, p=0.262 (cis)

Of the 9 rows above, 8 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 (Gamma-glutamyl hydrolase)
gnomAD constraint pLI=0.04, LOEUF=0.681 — LoF-tolerant
GWAS Catalog 36 unique SNPs / 69 rows
ClinVar 77 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx 11 clinical annotations across 4 drugs

Caveats declared by the tools

Sources

Provenance