CausalSentinel

Protein Dossier — COL1A1 (Collagen alpha-1(I) 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
Body mass index (BMI) -0.0267 0.00685 1.00e-04 Inverse variance weighted 2 trans NA
Body mass index (BMI) -0.0267 0.00685 1.00e-04 Inverse variance weighted 2 trans NA
Serum creatinine (eGFRcrea) -0.0114 0.00328 5.05e-04 Wald ratio 1 trans NA
Weight -0.0236 0.00801 0.00322 Inverse variance weighted 2 trans NA
Weight -0.0236 0.00801 0.00322 Inverse variance weighted 2 trans NA
Subjective well being -0.0285 0.0107 0.00766 Wald ratio 1 trans NA
Forced expiratory volume in 1-second (FEV1) -0.015 0.00593 0.0112 Inverse variance weighted 2 trans NA
Forced expiratory volume in 1-second (FEV1) -0.015 0.00593 0.0112 Inverse variance weighted 2 trans NA
Chronic kidney disease 0.132 0.0535 0.0136 Wald ratio 1 trans NA
Neo-openness to experience 0.626 0.258 0.0153 Wald ratio 1 trans NA
HbA1C -0.0289 0.0125 0.0207 Wald ratio 1 trans NA
Mean cell volume 0.213 0.0934 0.0222 Wald ratio 1 trans NA
…and 157 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

17 association rows across 12 traits (13 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
Circulating COL1A1 levels 3e-55 rs147266928 2 GCST90859986 no MR -> candidate analysis
COL1A1 protein levels 1e-45 rs147266928 2 GCST90468813 no MR -> candidate analysis
Estimated bone mineral density 2e-31 rs79409705 1 GCST90726625 no MR -> candidate analysis
Heel bone mineral density 7e-24 rs79409705 3 GCST006979 MR: beta=-0.0234, p=0.142 (trans)
Corneal resistance factor (MTAG) 1e-18 rs2586494 1 GCST90102517 no MR -> candidate analysis
Central corneal thickness (MTAG) 1e-13 rs2586494 1 GCST90102518 no MR -> candidate analysis
Total PHF-tau (SNP x SNP interaction) 4e-12 rs2857396 x rs2121005 1 GCST010340 no MR -> candidate analysis
Keratoconus 3e-9 rs2075556 1 GCST90013442 no MR -> candidate analysis
Blood cell traits (multivariate analysis) 1e-8 rs3840870 1 GCST008338 no MR -> candidate analysis
Breast cancer 8e-8 rs2075555 1 GCST000079 MR: beta=0.0639, p=0.102 (trans)
Opioid addiction 8e-7 rs1800695 2 GCST90244556 no MR -> candidate analysis
Memory decline 4e-6 rs28574643 1 GCST90448861 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 4642 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
osteogenesis imperfecta type 2 0.951 established (curated) no MR -> candidate analysis
osteogenesis imperfecta type 4 0.934 established (curated) no MR -> candidate analysis
osteogenesis imperfecta type 3 0.936 established (curated) no MR -> candidate analysis
osteogenesis imperfecta type 1 0.937 established (curated) no MR -> candidate analysis
osteogenesis imperfecta 0.937 0.911 established (curated) no MR -> candidate analysis
Caffey disease 0.847 established (curated) no MR -> candidate analysis
Ehlers-Danlos syndrome, arthrochalasic type 0.867 established (curated) no MR -> candidate analysis
combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 0.928 established (curated) no MR -> candidate analysis
Ehlers-Danlos syndrome, arthrochalasia type 0.867 established (curated) no MR -> candidate analysis
osteoporosis 0.92 established (curated) MR: beta=-0.0731, p=0.219 (trans)
Ehlers-Danlos syndrome, classic type 0.596 established (curated) no MR -> candidate analysis
Ehlers-Danlos syndrome, classic type, 1 0.292 established (curated) no MR -> candidate analysis
Ehlers-Danlos syndrome 0.772 established (curated) no MR -> candidate analysis
bone disorder 0.906 0.906 exploratory rare-variant signal MR: beta=0.23, p=0.36 (trans)
osteochondrodysplasia 0.891 0.891 exploratory rare-variant signal no MR -> candidate analysis

Of the 15 rows above, 13 have no MR estimate in this resource. Across all retrieved diseases for this gene: 4 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 0 known modulators (COL1A1 promoter)
gnomAD constraint pLI=1, LOEUF=0.155 — LoF-INTOLERANT
GWAS Catalog 50 unique SNPs / 100 rows
ClinVar 3890 records; 13 pathogenic in sample of 30
PharmGKB/ClinPGx 2 clinical annotations across 2 drugs

Caveats declared by the tools

Sources

Provenance