CausalSentinel

Protein Dossier — COL6A1 (Collagen alpha-1(VI) chain)

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
Eye problems or disorders: Injury or trauma resulting in loss of vision 0.326 0.11 0.00303 Wald ratio 1 cis NA
Mean platelet volume 0.0132 0.0052 0.0109 Wald ratio 1 cis NA
Height 0.034 0.0142 0.0164 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.285 0.12 0.0173 Wald ratio 1 cis NA
Ischemic stroke -0.186 0.0789 0.0186 Wald ratio 1 cis NA
Diagnoses - main ICD10: M54 Dorsalgia -0.276 0.12 0.0214 Wald ratio 1 cis NA
Weight 0.0224 0.0102 0.0275 Wald ratio 1 cis NA
Lung adenocarcinoma 0.297 0.139 0.0326 Wald ratio 1 cis NA
Fractured bone site(s): Arm 0.203 0.0957 0.0342 Wald ratio 1 cis NA
Non-cancer illness code self-reported: retinal detachment 0.313 0.151 0.0382 Wald ratio 1 cis NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.188 0.0912 0.0387 Wald ratio 1 cis NA
Years of schooling 0.0378 0.0189 0.0455 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

98 association rows across 56 traits (84 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
Collagen alpha-1(VI) chain levels 5e-5385 rs13053065 2 GCST90247085 no MR -> candidate analysis
Collagen alpha-1(VI) chain (analyte X16828.8) levels 3e-457 rs1053312 1 GCST90422875 no MR -> candidate analysis
Collagen alpha-1(VI) chain level in Chronic kidney disease w 8e-181 rs1053312 1 GCST90234582 no MR -> candidate analysis
Height 1e-130 rs8130733 6 GCST90245848 MR: beta=0.034, p=0.0164 (cis)
Corneal resistance factor 1e-101 rs142493024 9 GCST011390 no MR -> candidate analysis
Corneal resistance factor (MTAG) 1e-99 rs142493024 4 GCST90102517 no MR -> candidate analysis
Corneal hysteresis 8e-98 rs142493024 2 GCST011391 no MR -> candidate analysis
Central corneal thickness (MTAG) 4e-73 rs142493024 3 GCST90102518 no MR -> candidate analysis
Serum levels of protein COL6A1 5e-61 rs2150458 2 GCST90086571 no MR -> candidate analysis
Protein kinase C and casein kinase substrate in neurons prot 5e-49 rs1053315 1 GCST90439307 no MR -> candidate analysis
Corneal curvature 2e-40 rs13050142 3 GCST90012795 no MR -> candidate analysis
Valine–tRNA ligase levels 2e-38 rs13051496 1 GCST90422069 no MR -> candidate analysis
…and 44 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 823 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
Bethlem myopathy 1A 0.947 established (curated) no MR -> candidate analysis
Ullrich congenital muscular dystrophy 1A 0.916 established (curated) no MR -> candidate analysis
Bethlem myopathy 0.878 established (curated) no MR -> candidate analysis
Congenital muscular dystrophy, Ullrich type 0.863 established (curated) no MR -> candidate analysis
collagen 6-related myopathy 0.837 established (curated) no MR -> candidate analysis
hereditary disease 0.817 established (curated) no MR -> candidate analysis
diverticular disease 0.803 common-variant locus MR: beta=-0.188, p=0.16 (cis)
Abnormality of the musculature 0.761 established (curated) no MR -> candidate analysis
myopathy 0.559 established (curated) no MR -> candidate analysis
Ullrich congenital muscular dystrophy 0.608 established (curated) no MR -> candidate analysis
Sensorimotor neuropathy 0.559 established (curated) no MR -> candidate analysis
glaucoma 0.54 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.461 common-variant locus no MR -> candidate analysis
intestinal disorder 0.472 common-variant locus no MR -> candidate analysis
response to stimulus 0.465 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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 2 known modulators (Collagen)
gnomAD constraint pLI=4.4e-12, LOEUF=0.662 — LoF-tolerant
GWAS Catalog 75 unique SNPs / 139 rows
ClinVar 2252 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance