CausalSentinel

Protein Dossier — FMOD (Fibromodulin)

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
Diagnoses - main ICD10: I30 Acute pericarditis 1.11 0.313 4.09e-04 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.175 0.0522 7.87e-04 Wald ratio 1 cis NA
Body mass index (BMI) -0.0475 0.0148 0.00137 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.372 0.143 0.00907 Wald ratio 1 cis NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation 0.214 0.0841 0.0108 Wald ratio 1 cis NA
Weight -0.0317 0.0131 0.0155 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.0343 0.0142 0.0156 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gout 0.226 0.1 0.0245 Wald ratio 1 cis NA
Pulse rate -0.0553 0.0262 0.0351 Wald ratio 1 cis NA
Systolic blood pressure automated reading 0.0311 0.0152 0.041 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated -0.0391 0.0192 0.0418 Wald ratio 1 cis NA
Depressive symptoms -0.04 0.02 0.0455 Wald ratio 1 cis NA
…and 70 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

32 association rows across 19 traits (27 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
CHIT1 protein levels 6e-101 rs11581135 8 GCST90468744 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 1e-64 rs12060494 1 GCST90838669 no MR -> candidate analysis
Height 6e-35 rs1891174 3 GCST90245848 no MR -> candidate analysis
fibromodulin levels 6e-33 rs12077300 2 GCST90426652 no MR -> candidate analysis
PRELP protein levels 3e-29 rs142901388 3 GCST90470321 no MR -> candidate analysis
CHI3L1 protein levels 6e-20 rs10920621 2 GCST90468743 no MR -> candidate analysis
OPTC protein levels 3e-18 rs7410962 1 GCST90470128 no MR -> candidate analysis
Serum levels of protein FMOD 4e-13 rs4971252 1 GCST90089371 no MR -> candidate analysis
fibromodulin level in Chronic kidney disease with hypertensi 1e-12 rs6661575 1 GCST90238227 no MR -> candidate analysis
Body mass index 2e-9 rs16851349 1 GCST90662887 MR: beta=-0.0475, p=0.00137 (cis)
Osteoarthritis (hip) 9e-9 rs1977810 1 GCST90566798 no MR -> candidate analysis
Blood protein levels 3e-8 rs4971253 1 GCST006585 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 1022 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
Abnormality of the skeletal system 0.575 common-variant locus no MR -> candidate analysis
temporomandibular joint disorder 0.432 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.433 common-variant locus no MR -> candidate analysis
benign neoplasm of pituitary gland 0.287 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=0.0038, LOEUF=0.854 — LoF-tolerant
GWAS Catalog 64 unique SNPs / 128 rows
ClinVar 87 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance