CausalSentinel

Protein Dossier — OAS1 (2’-5’-oligoadenylate synthase 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
Body mass index (BMI) -0.034 0.00933 2.66e-04 Wald ratio 1 cis NA
Alzheimer’s disease -0.226 0.0629 3.33e-04 Wald ratio 1 cis NA
Weight -0.0245 0.00824 0.00298 Wald ratio 1 cis NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia 0.177 0.0629 0.00486 Wald ratio 1 cis NA
Systemic lupus erythematosus -0.475 0.177 0.00739 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis 0.189 0.0732 0.00989 Wald ratio 1 cis NA
Sodium in urine -0.0233 0.00918 0.0113 Wald ratio 1 cis NA
Fractured bone site(s): Wrist 0.146 0.0578 0.0113 Wald ratio 1 cis NA
Height -0.0289 0.0115 0.0119 Wald ratio 1 cis NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal 0.15 0.0682 0.0276 Wald ratio 1 cis NA
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.225 0.103 0.0284 Wald ratio 1 cis NA
Neo-neuroticism 0.749 0.371 0.0433 Wald ratio 1 cis NA
…and 90 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

31 association rows across 23 traits (25 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
Gamma glutamyl transpeptidase 6e-44 rs11066453 1 GCST001234 no MR -> candidate analysis
2’-5’-oligoadenylate synthase 1 levels (OAS1.10361.25.3) 6e-26 rs4767027 1 GCST90240130 no MR -> candidate analysis
Urate levels 5e-19 rs11066453 1 GCST008972 no MR -> candidate analysis
ENDOU protein levels 7e-18 rs2660 1 GCST90469107 no MR -> candidate analysis
COVID-19 (hospitalized covid vs population) 3e-17 rs2660 3 GCST90270935 no MR -> candidate analysis
Height 2e-15 rs11066453 2 GCST90833050 MR: beta=-0.0289, p=0.0119 (cis)
COVID-19 (critical illness vs population) 3e-15 rs2660 4 GCST90270934 no MR -> candidate analysis
COVID-19 severity 1e-13 rs10774671 1 GCST90274862 no MR -> candidate analysis
COVID-19 (hospitalized vs population) 7e-13 rs10774679 2 GCST90134597 no MR -> candidate analysis
2’-5’-oligoadenylate synthase 1 levels 1e-12 rs1131454 1 GCST90421088 no MR -> candidate analysis
Alcoholic liver damage (PheCode 317.11) 1e-11 rs11066453 1 GCST90651116 no MR -> candidate analysis
SARS-CoV-2 infection 2e-11 rs10774671 2 GCST90095125 no MR -> candidate analysis
…and 11 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 375 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
pulmonary alveolar proteinosis with hypogammaglobulinemia 0.738 established (curated) no MR -> candidate analysis
COVID-19 0.889 common-variant locus no MR -> candidate analysis
respiratory failure 0.537 common-variant locus no MR -> candidate analysis
middle ear disorder 0.485 common-variant locus no MR -> candidate analysis
Abnormal mastoid morphology 0.485 common-variant locus no MR -> candidate analysis
spinal cord injury 0.472 common-variant locus no MR -> candidate analysis
age-related macular degeneration 0.464 common-variant locus no MR -> candidate analysis
systemic lupus erythematosus 0.407 common-variant locus MR: beta=-0.475, p=0.00739 (cis)
osteoarthritis 0.409 common-variant locus MR: beta=-0.0266, p=0.407 (cis)
alcohol drinking 0.244 common-variant locus no MR -> candidate analysis
gout 0.225 common-variant locus no MR -> candidate analysis
alcoholic liver diseases 0.208 common-variant locus no MR -> candidate analysis
major depressive disorder 0.189 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.038 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.114 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 13 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-05, LOEUF=0.876 — LoF-tolerant
GWAS Catalog 83 unique SNPs / 166 rows
ClinVar 404 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance