CausalSentinel

Protein Dossier — GRP (Gastrin-releasing peptide)

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
Major depressive disorder -0.175 0.0933 0.0603 Wald ratio 1 trans NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0425 0.0262 0.105 Wald ratio 1 trans NA
Rheumatoid arthritis -0.118 0.0793 0.136 Wald ratio 1 trans NA
Squamous cell lung cancer -0.173 0.125 0.167 Wald ratio 1 trans NA
Hip osteoarthritis 0.128 0.102 0.208 Wald ratio 1 trans NA
Platelet count 37.1 30.4 0.222 Wald ratio 1 trans NA
Invasive mucinous ovarian cancer -0.193 0.158 0.223 Wald ratio 1 trans NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0377 0.0314 0.23 Wald ratio 1 trans NA
Primary sclerosing cholangitis -0.141 0.118 0.234 Wald ratio 1 trans NA
Depressive symptoms 0.0153 0.0138 0.267 Wald ratio 1 trans NA
Knee and hip osteoarthritis 0.0787 0.0744 0.29 Wald ratio 1 trans NA
Birth weight -0.0156 0.0149 0.293 Wald ratio 1 trans NA
…and 7 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

80 association rows across 49 traits (63 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
GRP protein levels 1e-55 rs9952787 6 GCST90469406 no MR -> candidate analysis
Body mass index 2e-25 rs7243357 17 GCST90255621 no MR -> candidate analysis
Weight (maximum, inv-normal transformed) 3e-23 rs1517036 1 GCST90480726 no MR -> candidate analysis
Body mass index (BMI, maximum, inv-normal transformed) 3e-21 rs55932597 1 GCST90479521 no MR -> candidate analysis
Body mass index (MTAG) 2e-20 rs7243357 1 GCST90179150 no MR -> candidate analysis
Height 3e-20 rs7230581 1 GCST90245848 no MR -> candidate analysis
Weight (mean, inv-normal transformed) 4e-20 rs1517036 1 GCST90480727 no MR -> candidate analysis
Type 2 diabetes 5e-19 rs9957320 7 GCST90492734 no MR -> candidate analysis
Body mass index (BMI, mean, inv-normal transformed) 1e-18 rs55932597 1 GCST90479522 no MR -> candidate analysis
Circulating PON3 levels 5e-17 rs8091691 1 GCST90859987 no MR -> candidate analysis
Metabolic syndrome 2e-16 rs7243357 1 GCST90444487 no MR -> candidate analysis
Weight 2e-16 rs9951619 1 GCST90662910 MR: beta=-0.0156, p=0.293 (trans)
…and 37 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 559 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
type 2 diabetes mellitus 0.858 common-variant locus no MR -> candidate analysis
obesity disorder 0.806 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.801 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.752 common-variant locus no MR -> candidate analysis
morbid obesity 0.686 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.552 common-variant locus no MR -> candidate analysis
overnutrition 0.538 common-variant locus no MR -> candidate analysis
conduction system disorder 0.473 common-variant locus no MR -> candidate analysis

Of the 8 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 (Gastrin-releasing peptide receptor)
gnomAD constraint pLI=0.0003, LOEUF=1.44 — LoF-tolerant
GWAS Catalog 55 unique SNPs / 110 rows
ClinVar 104 records; 12 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance