CausalSentinel

Protein Dossier — VWA2 (von Willebrand factor A domain-containing protein 2)

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
Pallidum volume -30.3 7.83 1.10e-04 Wald ratio 1 cis NA
Weight 0.0297 0.00811 2.47e-04 Wald ratio 1 cis NA
Fractured bone site(s): Wrist 0.177 0.0551 0.00134 Wald ratio 1 cis NA
Body mass index (BMI) 0.0293 0.00919 0.00143 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0395 0.0152 0.00962 Wald ratio 1 cis NA
Parkinson’s disease -0.392 0.154 0.0109 Wald ratio 1 cis NA
Birth weight 0.0353 0.0144 0.0142 Wald ratio 1 cis NA
Eye problems or disorders: Injury or trauma resulting in loss of vision 0.226 0.0967 0.0193 Wald ratio 1 cis NA
Neuroticism -0.0255 0.0116 0.0278 Wald ratio 1 cis NA
Transferrin -0.0838 0.0385 0.0297 Wald ratio 1 cis NA
Putamen volume -52 24.7 0.0353 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.207 0.103 0.0442 Wald ratio 1 cis NA
…and 99 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

16 association rows across 8 traits (14 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
Serum levels of protein VWA2 6e-39 rs597371 3 GCST90089677 no MR -> candidate analysis
von Willebrand factor A domain-containing protein 2 levels 4e-35 rs12572135 4 GCST90426925 no MR -> candidate analysis
Lymphocyte count 5e-18 rs66518778 2 GCST90002316 no MR -> candidate analysis
Free Cholesterol to Cholesteryl Esters in Small HDL ratio 5e-12 rs11816667 1 GCST90827928 no MR -> candidate analysis
Monocyte count 3e-11 rs138243320 2 GCST90002340 no MR -> candidate analysis
Body mass index 6e-10 rs9664945 2 GCST90255621 MR: beta=0.0293, p=0.00143 (cis)
Height 1e-8 rs10885543 1 GCST90245848 MR: beta=0.0155, p=0.163 (cis)
Oligodendroglioma 9e-6 rs9665610 1 GCST90296472 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 60 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
ocular hypotension 0.465 common-variant locus no MR -> candidate analysis
placenta praevia 0.465 common-variant locus no MR -> candidate analysis
vesicoureteral reflux 0.426 established (curated) no MR -> candidate analysis
streptococcal infection 0.395 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.2 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.169 common-variant locus no MR -> candidate analysis
essential hypertension 0.144 common-variant locus no MR -> candidate analysis
insomnia 0.076 common-variant locus no MR -> candidate analysis
neuroendocrine neoplasm 0.051 common-variant locus no MR -> candidate analysis
cardiovascular disorder 0.045 common-variant locus no MR -> candidate analysis
lysosomal lipid storage disorder 0.042 common-variant locus no MR -> candidate analysis
peripheral vascular disease 0.04 common-variant locus no MR -> candidate analysis
Hirsutism 0.039 common-variant locus no MR -> candidate analysis

Of the 13 rows above, 13 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 (Integrator complex subunit 6)
gnomAD constraint pLI=3.9e-26, LOEUF=1.26 — LoF-tolerant
GWAS Catalog 49 unique SNPs / 103 rows
ClinVar 106 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance