CausalSentinel

Protein Dossier — ADAM15 (Disintegrin and metalloproteinase domain-containing protein 15)

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
Non-cancer illness code self-reported: high cholesterol -0.243 0.0526 3.74e-06 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) 0.051 0.0131 1.04e-04 Wald ratio 1 trans NA
Forced vital capacity (FVC) 0.0445 0.0125 3.57e-04 Wald ratio 1 trans NA
Systolic blood pressure automated reading -0.0511 0.0155 0.00102 Wald ratio 1 trans NA
Body mass index (BMI) -0.0449 0.0152 0.00313 Wald ratio 1 trans NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.276 0.111 0.0127 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension -0.069 0.0278 0.0131 Wald ratio 1 trans NA
Bulimia nervosa -0.106 0.0437 0.0152 Wald ratio 1 trans NA
Endometrioid ovarian cancer -0.454 0.188 0.0158 Wald ratio 1 trans NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.224 0.0928 0.0159 Wald ratio 1 trans NA
Non-cancer illness code self-reported: psoriasis 0.252 0.113 0.0255 Wald ratio 1 trans NA
Lumbar spine bone mineral density -0.119 0.0555 0.0313 Wald ratio 1 trans NA
…and 63 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

102 association rows across 76 traits (97 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 ADAM15 levels 4e-3324 rs11589479 6 GCST90860707 no MR -> candidate analysis
Disintegrin and metalloproteinase domain-containing protein 2e-207 rs11589479 2 GCST90059897 no MR -> candidate analysis
Cerebrospinal fluid protein ADAM15 levels 9e-120 rs41264285 1 GCST90942994 no MR -> candidate analysis
Vertex-wise sulcal depth 6e-78 rs11589479 1 GCST90095129 no MR -> candidate analysis
ADAM15 protein levels 4e-55 rs114498585 3 GCST90468217 no MR -> candidate analysis
Albumin levels 2e-50 rs11589479 8 GCST90662901 no MR -> candidate analysis
Sushi, von Willebrand factor type A, EGF and pentraxin domai 2e-49 rs45444697 1 GCST90249743 no MR -> candidate analysis
Serum albumin levels 2e-42 rs11589479 2 GCST90018945 no MR -> candidate analysis
hematocrit (mean, inv-norm transformed) 3e-34 rs6660884 1 GCST90475341 no MR -> candidate analysis
Urea levels 1e-32 rs6427128 1 GCST90019525 no MR -> candidate analysis
hemoglobin (maximum, inv-norm transformed) 2e-32 rs6660884 1 GCST90475372 no MR -> candidate analysis
Height 4e-32 rs2306125 1 GCST90245848 no MR -> candidate analysis
…and 64 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 452 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
Varicose veins 0.652 common-variant locus no MR -> candidate analysis
open-angle glaucoma 0.623 common-variant locus no MR -> candidate analysis
substance abuse 0.49 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.49 common-variant locus no MR -> candidate analysis
lymphatic system disorder 0.458 common-variant locus no MR -> candidate analysis
vein disorder 0.458 common-variant locus no MR -> candidate analysis
actinic keratosis 0.458 common-variant locus no MR -> candidate analysis
kidney failure 0.417 common-variant locus no MR -> candidate analysis
COVID-19 0.373 common-variant locus no MR -> candidate analysis
systemic lupus erythematosus 0.366 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.257 common-variant locus no MR -> candidate analysis
metabolic dysfunction-associated steatotic liver disease 0.134 common-variant locus no MR -> candidate analysis
bladder exstrophy 0.132 common-variant locus no MR -> candidate analysis
obesity disorder 0.123 common-variant locus no MR -> candidate analysis

Of the 14 rows above, 14 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 (Disintegrin and metalloproteinase domain-containing protein 15)
gnomAD constraint pLI=2.2e-17, LOEUF=0.818 — LoF-tolerant
GWAS Catalog 138 unique SNPs / 334 rows
ClinVar 224 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance