CausalSentinel

Protein Dossier — TFF1 (Trefoil factor 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
Non-cancer illness code self-reported: vitiligo 1.17 0.265 1.04e-05 Wald ratio 1 cis NA
Birth weight -0.0576 0.02 0.0039 Wald ratio 1 cis NA
Hippocampus volume -71.5 25.4 0.00484 Wald ratio 1 cis NA
Pulse rate 0.056 0.0228 0.0142 Wald ratio 1 cis NA
Eye problems or disorders: Injury or trauma resulting in loss of vision 0.307 0.126 0.015 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.114 0.0476 0.0172 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.166 0.0743 0.0255 Wald ratio 1 cis NA
Non-cancer illness code self-reported: iron deficiency anaemia 0.265 0.139 0.0578 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.119 0.0653 0.0678 Wald ratio 1 cis NA
Diagnoses - main ICD10: L03 Cellulitis 0.213 0.118 0.0722 Wald ratio 1 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter -0.285 0.169 0.091 Wald ratio 1 cis NA
Rheumatoid arthritis 0.138 0.084 0.0999 Wald ratio 1 cis NA
…and 57 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

19 association rows across 13 traits (18 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
TFF1/TFF2 protein level ratio 3e-514 rs184432 1 GCST90315914 no MR -> candidate analysis
Trefoil factor 1 levels 5e-111 rs3761376 4 GCST90249813 no MR -> candidate analysis
Circulating TFF2 levels 1e-90 rs225344 3 GCST90860338 no MR -> candidate analysis
Serum levels of protein TFF1 1e-75 rs3761376 1 GCST90090541 no MR -> candidate analysis
TFF1 protein levels 2e-55 rs117389225 2 GCST90470835 no MR -> candidate analysis
Blood protein levels 6e-42 rs3761376 1 GCST006585 no MR -> candidate analysis
TFF3 protein levels 5e-35 rs4920094 1 GCST90470837 no MR -> candidate analysis
Trefoil factor 1 levels (TFF1.9185.15.3) 4e-14 rs3761376 1 GCST90243108 no MR -> candidate analysis
TFF2 protein levels 1e-13 rs12626926 1 GCST90470836 no MR -> candidate analysis
Pancreatic cancer 4e-13 rs1547374 1 GCST001350 no MR -> candidate analysis
Cerebrospinal fluid protein TFF1 levels 3e-12 rs3761376 1 GCST90944910 no MR -> candidate analysis
Thyroid stimulating hormone levels 4e-8 rs178740 1 GCST90572789 no MR -> candidate analysis
…and 1 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 315 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
exocrine pancreatic carcinoma 0.236 common-variant locus no MR -> candidate analysis

Of the 1 rows above, 1 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=0.00091, LOEUF=1.87 — LoF-tolerant
GWAS Catalog 69 unique SNPs / 138 rows
ClinVar 113 records; 14 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance