CausalSentinel

Protein Dossier — WFDC1 (WAP four-disulfide core domain protein 1)

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
Age at menarche -0.0554 0.0166 8.30e-04 Wald ratio 1 cis NA
Microalbuminuria -0.202 0.0643 0.0017 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.176 0.0678 0.00921 Wald ratio 1 cis NA
Packed cell volume -0.144 0.0592 0.0152 Wald ratio 1 cis NA
Eye problems or disorders: Injury or trauma resulting in loss of vision 0.179 0.076 0.0184 Wald ratio 1 cis NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.478 0.216 0.0265 Wald ratio 1 cis NA
Knee and hip osteoarthritis -0.129 0.0585 0.0271 Wald ratio 1 cis NA
Invasive mucinous ovarian cancer -0.251 0.114 0.0278 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) 0.0131 0.00599 0.029 Wald ratio 1 cis NA
Knee osteoarthritis -0.171 0.0783 0.0294 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol -0.0401 0.0195 0.0398 Wald ratio 1 cis NA
Systemic lupus erythematosus -0.255 0.132 0.0539 Wald ratio 1 cis NA
…and 91 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

21 association rows across 19 traits (11 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
WAP four-disulfide core domain protein 1 levels 1e-212 rs400345 2 GCST90250205 no MR -> candidate analysis
Serum levels of protein WFDC1 9e-98 rs400345 1 GCST90090626 no MR -> candidate analysis
Blood protein levels 6e-54 rs400345 1 GCST006585 no MR -> candidate analysis
WAP four-disulfide core domain protein 1 level in Chronic ki 3e-26 rs400345 1 GCST90239308 no MR -> candidate analysis
Circulating SFTPD levels 4e-23 rs12919513 1 GCST90859954 no MR -> candidate analysis
WFDC1 protein levels 7e-18 rs62048609 1 GCST90471074 no MR -> candidate analysis
Cerebrospinal fluid protein WFDC1 levels 3e-17 rs12599383 1 GCST90944063 no MR -> candidate analysis
Height 2e-13 rs8063863 2 GCST90245848 MR: beta=0.0153, p=0.0769 (cis)
Gestational length in nulliparas 4e-9 rs2550487 1 GCST90429687 no MR -> candidate analysis
Gut microbial network clusters (Sienna (at 1 year) x Any Hou 6e-8 rs72802651 1 GCST90569872 no MR -> candidate analysis
Systolic blood pressure (alcohol consumption interaction) 1e-7 rs16963349 1 GCST002307 no MR -> candidate analysis
Metabolite levels 4e-7 rs9910 1 GCST009391 no MR -> candidate analysis
…and 7 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 90 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
major salivary gland cancer 0.459 common-variant locus no MR -> candidate analysis
musculoskeletal system disorder 0.452 common-variant locus no MR -> candidate analysis
Vertigo 0.389 common-variant locus no MR -> candidate analysis
neuroendocrine neoplasm 0.055 common-variant locus no MR -> candidate analysis

Of the 4 rows above, 4 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=8.1e-16, LOEUF=1.55 — LoF-tolerant
GWAS Catalog 55 unique SNPs / 110 rows
ClinVar 147 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance