CausalSentinel

Protein Dossier — GLO1 (Lactoylglutathione lyase)

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
Body mass index (BMI) 0.0584 0.0147 7.60e-05 Wald ratio 1 cis NA
Weight 0.0471 0.013 3.00e-04 Wald ratio 1 cis NA
Sleep duration 0.0347 0.0115 0.0026 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia 0.432 0.148 0.00345 Wald ratio 1 cis NA
Cancer code self-reported: prostate cancer 0.357 0.123 0.00376 Wald ratio 1 cis NA
Myocardial infarction 0.186 0.069 0.00693 Wald ratio 1 cis NA
Cigarettes smoked per day -1.27 0.495 0.0105 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.194 0.0787 0.0137 Wald ratio 1 cis NA
Eye problems or disorders: Cataract 0.159 0.0692 0.0213 Wald ratio 1 cis NA
Lung adenocarcinoma 0.352 0.167 0.0349 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities 0.178 0.087 0.0412 Wald ratio 1 cis NA
Diagnoses - main ICD10: K20 Oesophagitis 0.236 0.12 0.0491 Wald ratio 1 cis NA
…and 86 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

19 association rows across 15 traits (15 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
GLO1/GLOD4 protein level ratio 1e-948 rs4746 1 GCST90314934 no MR -> candidate analysis
Circulating GLO1 levels 3e-718 rs4714175 2 GCST90859780 no MR -> candidate analysis
GLO1/S100A4 protein level ratio 5e-647 rs4746 1 GCST90314935 no MR -> candidate analysis
Cerebrospinal fluid protein GLO1 levels 2e-95 rs4746 1 GCST90943424 no MR -> candidate analysis
Lactoylglutathione lyase levels 5e-51 rs4746 2 GCST90179310 no MR -> candidate analysis
Serum levels of protein GLO1 1e-15 rs13200763 1 GCST90090884 no MR -> candidate analysis
MDGA1 protein levels 8e-14 rs114306573 1 GCST90469875 no MR -> candidate analysis
GLO1 protein levels 2e-12 rs4746 1 GCST90277607 no MR -> candidate analysis
Insomnia 1e-11 rs7747615 3 GCST90131901 no MR -> candidate analysis
Blood protein levels 7e-11 rs12209477 1 GCST006585 no MR -> candidate analysis
LGUL protein level (protein group normalized intensity) 2e-9 rs4714175 1 GCST90570960 no MR -> candidate analysis
Gut microbiome abundance (class Clostridium sensu stricto sp 1e-7 rs1616723 1 GCST90569614 no MR -> candidate analysis
…and 3 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 384 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
migraine disorder 0.423 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.128 common-variant locus no MR -> candidate analysis
placenta praevia 0.126 common-variant locus no MR -> candidate analysis
stroke disorder 0.111 common-variant locus no MR -> candidate analysis
alcohol drinking 0.111 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.11 common-variant locus no MR -> candidate analysis
type 1 diabetes nephropathy 0.109 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 7 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 (Lactoylglutathione lyase)
gnomAD constraint pLI=8.4e-11, LOEUF=1.48 — LoF-tolerant
GWAS Catalog 34 unique SNPs / 68 rows
ClinVar 25 records; 6 pathogenic in sample of 25
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance