CausalSentinel

Protein Dossier — COL15A1 (Collagen alpha-1(XV) 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
Height -0.0698 0.0131 1.08e-07 Wald ratio 1 cis 0.845
Serum cystatin C (eGFRcys) -0.0267 0.00821 0.00115 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.301 0.0936 0.00132 Wald ratio 1 cis NA
Packed cell volume -0.22 0.0755 0.00352 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0251 0.00884 0.00452 Wald ratio 1 cis NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] -0.294 0.105 0.00536 Wald ratio 1 cis NA
Haemoglobin concentration -0.0661 0.0242 0.00636 Wald ratio 1 cis NA
Neo-conscientiousness -0.864 0.326 0.00802 Wald ratio 1 cis NA
Serum creatinine (eGFRcrea) 0.00944 0.00378 0.0124 Wald ratio 1 cis NA
Red blood cell count -0.0222 0.00944 0.0189 Wald ratio 1 cis NA
Non-cancer illness code self-reported: iron deficiency anaemia 0.252 0.117 0.0308 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.0938 0.0437 0.0318 Wald ratio 1 cis NA
…and 98 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

82 association rows across 46 traits (71 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
COL15A1 protein levels 1e-168 rs10819566 3 GCST90468811 no MR -> candidate analysis
Height 2e-135 rs2075663 11 GCST90245848 MR: beta=-0.0698, p=1.08e-07 (cis)
Collagen alpha-1(XV) chain levels 2e-55 rs7857774 2 GCST90247088 no MR -> candidate analysis
height (minimum, inv-normal transformed) 1e-40 rs7034716 2 GCST90475365 no MR -> candidate analysis
A0A087X0K0;COFA1 protein level (protein group normalized int 9e-37 rs57410362 1 GCST90570762 no MR -> candidate analysis
Cerebrospinal fluid protein COL15A1 levels 6e-32 rs10988442 1 GCST90944719 no MR -> candidate analysis
Standing height (UKB data field 50) 7e-30 rs989393 1 GCST90468178 no MR -> candidate analysis
Pulse pressure 1e-24 rs2075663 12 GCST90292476 no MR -> candidate analysis
Core binding factor acute myeloid leukemia 2e-23 rs1010403; rs4742747; rs911932; rs3758312; rs7045933; rs6478963; rs1333869; rs16918095 2 GCST008413 no MR -> candidate analysis
Height (baseline) 5e-23 rs989393 2 GCST90565843 no MR -> candidate analysis
Collagen alpha-1(XV) chain levels (COL15A1.8974.172.3) 2e-19 rs41305481 1 GCST90240747 no MR -> candidate analysis
Serum levels of protein COL15A1 2e-18 rs12380469 1 GCST90090420 no MR -> candidate analysis
…and 34 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 397 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
atrial fibrillation 0.782 common-variant locus MR: beta=-0.128, p=0.278 (cis)
chronic obstructive pulmonary disease 0.761 common-variant locus no MR -> candidate analysis
hypothyroidism 0.644 common-variant locus MR: beta=0.0938, p=0.0318 (cis)
respiratory system disorder 0.505 common-variant locus no MR -> candidate analysis
asthma 0.451 common-variant locus no MR -> candidate analysis
Conductive hearing impairment 0.462 common-variant locus no MR -> candidate analysis
atrial flutter 0.46 common-variant locus MR: beta=-0.128, p=0.278 (cis)
psoriatic arthritis 0.445 common-variant locus no MR -> candidate analysis
deep vein thrombosis 0.403 common-variant locus no MR -> candidate analysis
cardiac arrest 0.421 common-variant locus no MR -> candidate analysis
Eczematoid dermatitis 0.406 common-variant locus no MR -> candidate analysis
Abnormal thrombosis 0.394 common-variant locus no MR -> candidate analysis
allergic disease 0.394 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.328 common-variant locus no MR -> candidate analysis

Of the 14 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 2 known modulators (Collagen)
gnomAD constraint pLI=3.3e-24, LOEUF=0.783 — LoF-tolerant
GWAS Catalog 104 unique SNPs / 222 rows
ClinVar 376 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance