CausalSentinel

Protein Dossier — APOA5 (Apolipoprotein A-V)

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
Non-cancer illness code self-reported: high cholesterol -1.11 0.113 6.33e-23 Wald ratio 1 cis 1
Coronary heart disease -0.19 0.0472 5.60e-05 Wald ratio 1 cis NA
Ulcerative colitis 0.262 0.0717 2.56e-04 Wald ratio 1 cis NA
Myocardial infarction -0.186 0.0528 4.39e-04 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina -0.375 0.112 8.04e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bladder problem (not cancer) 0.38 0.123 0.0021 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension -0.0723 0.0248 0.00353 Wald ratio 1 cis NA
Inflammatory bowel disease 0.158 0.0566 0.00514 Wald ratio 1 cis NA
Fasting glucose 0.0457 0.0168 0.00639 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gout -0.555 0.208 0.00762 Wald ratio 1 cis NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.103 0.0408 0.0113 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.287 0.123 0.0198 Wald ratio 1 cis NA
…and 81 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

1587 association rows across 618 traits (1554 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
Apolipoprotein A-V levels 1e-942 rs3135506 2 GCST90246544 no MR -> candidate analysis
Triglyceride levels 9e-814 rs651821 39 GCST90278645 no MR -> candidate analysis
Triglycerides 3e-611 rs651821 26 GCST90018755 no MR -> candidate analysis
Triglyceride to HDL cholesterol ratio 3e-326 rs6589567 5 GCST90295949 no MR -> candidate analysis
High density lipoprotein cholesterol levels 2e-317 rs651821 35 GCST90278635 no MR -> candidate analysis
Triglyceride levels (UKB data field 30870) 3e-302 rs45611741 3 GCST90468106 no MR -> candidate analysis
HDL cholesterol 6e-293 rs651821 5 GCST90018956 no MR -> candidate analysis
Monounsaturated fatty acid levels 9e-265 rs3135506 27 GCST90502030 no MR -> candidate analysis
HDL cholesterol levels 3e-247 rs651821 14 GCST90134519 no MR -> candidate analysis
Hypertriglyceridemia 5e-228 rs651821 11 GCST90244626 no MR -> candidate analysis
Metabolic syndrome cluster 4 (lipodystrophy-like endotype) 3e-210 rs662799 18 GCST90860771 no MR -> candidate analysis
Hypo-HDL-cholesterolemia 4e-164 rs2075291 9 GCST90244635 no MR -> candidate analysis
…and 606 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 287 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
hyperlipoproteinemia type V 0.83 established (curated) no MR -> candidate analysis
Hyperlipoproteinemia type 4 0.842 established (curated) no MR -> candidate analysis
hypertriglyceridemia 0.858 established (curated) no MR -> candidate analysis
metabolic syndrome 0.946 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.936 common-variant locus no MR -> candidate analysis
hyperlipidemia 0.929 common-variant locus no MR -> candidate analysis
metabolic disease 0.918 common-variant locus no MR -> candidate analysis
Hypercholesterolemia 0.917 common-variant locus MR: beta=-1.11, p=6.33e-23 (cis)
Abnormality of the cardiovascular system 0.904 established (curated) no MR -> candidate analysis
familial lipoprotein lipase deficiency 0.708 established (curated) no MR -> candidate analysis
familial hyperlipidemia 0.857 common-variant locus no MR -> candidate analysis
Decreased HDL cholesterol concentration 0.854 common-variant locus no MR -> candidate analysis
myocardial infarction 0.837 common-variant locus MR: beta=-0.186, p=4.39e-04 (cis)
small intestine neoplasm 0.842 0.842 exploratory rare-variant signal no MR -> candidate analysis
abdominal aortic aneurysm 0.833 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: 1 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=4.7e-08, LOEUF=1.13 — LoF-tolerant
GWAS Catalog 317 unique SNPs / 816 rows
ClinVar 375 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx 2 clinical annotations across 4 drugs

Caveats declared by the tools

Sources

Provenance