CausalSentinel

Protein Dossier — THSD1 (Thrombospondin type-1 domain-containing protein 1)

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
Myocardial infarction -0.107 0.0372 0.00391 Wald ratio 1 cis NA
Coronary heart disease -0.0962 0.0341 0.00477 Wald ratio 1 cis NA
Weight 0.014 0.00712 0.0495 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.0596 0.0313 0.0567 Wald ratio 1 cis NA
Non-cancer illness code self-reported: mania or bipolar disorder or manic depression 0.24 0.127 0.0585 Wald ratio 1 cis NA
Fractured bone site(s): Other bones -0.07 0.0377 0.0633 Wald ratio 1 cis NA
Cough on most days 0.0704 0.0386 0.0683 Wald ratio 1 cis NA
Eye problems or disorders: Cataract 0.0743 0.0408 0.0687 Wald ratio 1 cis NA
Non-cancer illness code self-reported: joint disorder 0.177 0.0999 0.0764 Wald ratio 1 cis NA
Forearm bone mineral density -0.245 0.143 0.0853 Wald ratio 1 cis NA
Birth weight 0.0211 0.0129 0.103 Wald ratio 1 cis NA
Diagnoses - main ICD10: R11 Nausea and vomiting -0.286 0.178 0.107 Wald ratio 1 cis NA
…and 42 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

4 association rows across 3 traits (4 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
Thrombospondin type-1 domain-containing protein 1 levels 3e-338 rs41292808 2 GCST90249866 no MR -> candidate analysis
THSD1 protein levels 4e-83 rs149590732 1 GCST90470859 no MR -> candidate analysis
Thrombospondin type-1 domain-containing protein 1 levels (TH 6e-33 rs41292808 1 GCST90243009 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 86 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
aneurysm, intracranial berry, 12 0.862 established (curated) no MR -> candidate analysis
lymphatic malformation 13 0.799 established (curated) no MR -> candidate analysis
Non-immune hydrops fetalis 0.596 established (curated) no MR -> candidate analysis
Familial cerebral saccular aneurysm 0.608 established (curated) no MR -> candidate analysis
Alzheimer disease 0.396 common-variant locus no MR -> candidate analysis
aortic aneurysm 0.195 established (curated) no MR -> candidate analysis
vascular dementia 0.182 established (curated) no MR -> candidate analysis
Abnormality of the skeletal system 0.041 common-variant locus no MR -> candidate analysis
cataract 0.04 common-variant locus MR: beta=0.0743, p=0.0687 (cis)
trauma complication 0.04 common-variant locus no MR -> candidate analysis

Of the 10 rows above, 9 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=4e-09, LOEUF=0.979 — LoF-tolerant
GWAS Catalog 9 unique SNPs / 18 rows
ClinVar 216 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance