CausalSentinel

Protein Dossier — COCH (Cochlin)

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
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 1.65 0.378 1.22e-05 Wald ratio 1 cis NA
Fractured bone site(s): Other bones 0.104 0.03 5.35e-04 Wald ratio 1 cis NA
Diastolic blood pressure automated reading -0.0228 0.00782 0.00353 Wald ratio 1 cis NA
LDL cholesterol -0.0456 0.0164 0.0054 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia 0.228 0.0922 0.0134 Wald ratio 1 cis NA
Neo-agreeableness -0.411 0.182 0.0243 Wald ratio 1 cis NA
HOMA-B 0.0231 0.0105 0.0278 Wald ratio 1 cis NA
Childhood intelligence 0.0874 0.0403 0.0303 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina 0.0846 0.0394 0.0318 Wald ratio 1 cis NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus -0.168 0.0804 0.0368 Wald ratio 1 cis NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal -0.142 0.0749 0.0583 Wald ratio 1 cis NA
Non-cancer illness code self-reported: mania or bipolar disorder or manic depression 0.229 0.121 0.0587 Wald ratio 1 cis NA
…and 77 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

26 association rows across 22 traits (20 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
COCH protein levels 5e-282 rs8015095 4 GCST90468810 no MR -> candidate analysis
Cochlin levels 2e-126 rs28400019 2 GCST90247106 no MR -> candidate analysis
Serum levels of protein COCH 5e-69 rs7159420 1 GCST90089749 no MR -> candidate analysis
Cochlin levels (COCH.7227.75.3) 1e-38 rs34907608 1 GCST90240729 no MR -> candidate analysis
Blood protein levels 2e-38 rs35561078 1 GCST006585 no MR -> candidate analysis
Vertex-wise cortical surface area 1e-20 rs8022032 1 GCST90095130 no MR -> candidate analysis
IDP dMRI TBSS OD Superior fronto-occipital fasciculus R 3e-18 rs10148294 1 GCST90004444 no MR -> candidate analysis
Cortical thickness 1e-17 rs8022032 1 GCST90091061 no MR -> candidate analysis
Vertex-wise cortical thickness 2e-17 rs8022032 1 GCST90095131 no MR -> candidate analysis
Hearing loss 2e-12 rs121908932 1 GCST90132907 no MR -> candidate analysis
A0A2U3TZE7;COCH protein level (protein group normalized inte 6e-11 rs8015095 1 GCST90570891 no MR -> candidate analysis
Mean platelet volume 2e-9 rs12897108 1 GCST004599 no MR -> candidate analysis
…and 10 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 271 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
autosomal dominant nonsyndromic hearing loss 0.836 established (curated) no MR -> candidate analysis
hearing loss, autosomal recessive 110 0.794 established (curated) no MR -> candidate analysis
nonsyndromic genetic hearing loss 0.683 established (curated) no MR -> candidate analysis
Rare genetic deafness 0.748 established (curated) no MR -> candidate analysis
Hearing impairment 0.581 established (curated) no MR -> candidate analysis
Sensorineural hearing impairment 0.559 established (curated) no MR -> candidate analysis
Prelingual sensorineural hearing impairment 0.547 established (curated) no MR -> candidate analysis
familial glucocorticoid deficiency 0.362 common-variant locus no MR -> candidate analysis
hereditary disease 0.316 established (curated) no MR -> candidate analysis
Usher syndrome 0.195 established (curated) no MR -> candidate analysis
placental retention 0.165 common-variant locus no MR -> candidate analysis

Of the 11 rows above, 11 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=1.9e-10, LOEUF=0.95 — LoF-tolerant
GWAS Catalog 48 unique SNPs / 96 rows
ClinVar 389 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance