CausalSentinel

Protein Dossier — ADM (Pro-adrenomedullin)

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
Eye problems or disorders: Glaucoma 0.00798 0.00263 0.00242 Inverse variance weighted 2 cis NA
Eye problems or disorders: Glaucoma 0.00798 0.00263 0.00242 Inverse variance weighted 2 trans NA
Forearm bone mineral density 0.134 0.0534 0.012 Inverse variance weighted 2 cis NA
Forearm bone mineral density 0.134 0.0534 0.012 Inverse variance weighted 2 trans NA
Eye problems or disorders: Cataract 0.00987 0.00421 0.0189 Inverse variance weighted 2 cis NA
Eye problems or disorders: Cataract 0.00987 0.00421 0.0189 Inverse variance weighted 2 trans NA
Hearing difficulty or problems: Yes -0.00753 0.00327 0.0212 Inverse variance weighted 2 cis NA
Hearing difficulty or problems: Yes -0.00753 0.00327 0.0212 Inverse variance weighted 2 trans NA
Diagnoses - main ICD10: R35 Polyuria -0.00106 0.000463 0.0219 Inverse variance weighted 2 cis NA
Diagnoses - main ICD10: R35 Polyuria -0.00106 0.000463 0.0219 Inverse variance weighted 2 trans NA
Serum cystatin C (eGFRcys) 0.0137 0.00658 0.0379 Inverse variance weighted 2 cis NA
Serum cystatin C (eGFRcys) 0.0137 0.00658 0.0379 Inverse variance weighted 2 trans NA
…and 181 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

28 association rows across 28 traits (26 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
Circulating ADM levels 2e-162 rs4641466 1 GCST90859743 no MR -> candidate analysis
Cholesteryl Esters in Small HDL 1e-50 rs56776911 1 GCST90501236 no MR -> candidate analysis
Cholesterol in Small HDL 2e-41 rs56776911 1 GCST90501234 no MR -> candidate analysis
Total lipids in small HDL 8e-31 rs56776911 1 GCST90501240 no MR -> candidate analysis
Phospholipids in small HDL 5e-29 rs56776911 1 GCST90501242 no MR -> candidate analysis
Phospholipids to Total Lipids in IDL percentage 1e-26 rs57153895 1 GCST90501130 no MR -> candidate analysis
Cholesteryl Esters in Medium HDL 3e-23 rs57153895 1 GCST90501184 no MR -> candidate analysis
Concentration of HDL particles 6e-23 rs57153895 1 GCST90501116 no MR -> candidate analysis
Cholesterol in Medium HDL 4e-21 rs57153895 1 GCST90501182 no MR -> candidate analysis
Total lipids in medium HDL 5e-19 rs57153895 1 GCST90501188 no MR -> candidate analysis
Concentration of medium HDL particles 3e-18 rs57153895 1 GCST90501189 no MR -> candidate analysis
Phospholipids in medium HDL 6e-18 rs57153895 1 GCST90501190 no MR -> candidate analysis
…and 16 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 1102 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
hypertensive disorder 0.656 common-variant locus no MR -> candidate analysis
Varicose veins 0.613 common-variant locus no MR -> candidate analysis
hemorrhoid 0.505 common-variant locus no MR -> candidate analysis
cardiovascular disorder 0.46 common-variant locus no MR -> candidate analysis
heart disorder 0.452 common-variant locus no MR -> candidate analysis
Increased blood pressure 0.44 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.4 common-variant locus no MR -> candidate analysis
lymphatic system disorder 0.374 common-variant locus no MR -> candidate analysis
vein disorder 0.374 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.338 common-variant locus no MR -> candidate analysis
congestive heart failure 0.286 common-variant locus no MR -> candidate analysis
preeclampsia 0.237 common-variant locus no MR -> candidate analysis
vascular disorder 0.246 common-variant locus no MR -> candidate analysis
osteoarthritis, knee 0.24 common-variant locus no MR -> candidate analysis
prolapse of female genital organ 0.24 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 (Pro-adrenomedullin)
gnomAD constraint pLI=0.24, LOEUF=1.02 — LoF-tolerant
GWAS Catalog 104 unique SNPs / 256 rows
ClinVar 46 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance