CausalSentinel

Protein Dossier — APOA1 (Apolipoprotein A-I)

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: hypothyroidism or myxoedema 0.107 0.0425 0.0118 Wald ratio 1 cis NA
Forearm bone mineral density -0.154 0.0705 0.0285 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis 0.132 0.0605 0.0289 Wald ratio 1 cis NA
Diagnoses - main ICD10: K20 Oesophagitis -0.27 0.144 0.061 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bladder problem (not cancer) 0.203 0.116 0.0785 Wald ratio 1 cis NA
LDL cholesterol -0.0445 0.0267 0.0956 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression 0.0661 0.0411 0.108 Wald ratio 1 cis NA
Alzheimer’s disease 0.197 0.123 0.108 Wald ratio 1 cis NA
Non-cancer illness code self-reported: mania or bipolar disorder or manic depression 0.264 0.166 0.111 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hiatus hernia -0.123 0.0796 0.121 Wald ratio 1 cis NA
Hippocampus volume -35.2 22.8 0.122 Wald ratio 1 cis NA
Femoral neck bone mineral density -0.0534 0.0352 0.13 Wald ratio 1 cis NA
…and 57 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

453 association rows across 261 traits (450 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
Phospholipids in small HDL 4e-419 rs525028 3 GCST90501242 no MR -> candidate analysis
Total lipids in small HDL 3e-407 rs525028 3 GCST90501240 no MR -> candidate analysis
Free cholesterol in small HDL 3e-402 rs525028 5 GCST90501238 no MR -> candidate analysis
Apolipoprotein A1 levels 7e-331 rs613808 6 GCST010241 no MR -> candidate analysis
Triglyceride levels (MTAG) 6e-304 rs2070665 1 GCST90179149 no MR -> candidate analysis
Apolipoprotein A levels (UKB data field 30630) 3e-295 rs613808 1 GCST90468061 no MR -> candidate analysis
Concentration of small HDL particles 9e-277 rs525028 4 GCST90501241 no MR -> candidate analysis
Phosphoglycerides levels 1e-257 rs525028 5 GCST90501228 no MR -> candidate analysis
Phosphatidylcholine levels 2e-256 rs525028 5 GCST90501227 no MR -> candidate analysis
Cholesterol in Small HDL 1e-221 rs613808 2 GCST90501234 no MR -> candidate analysis
Concentration of HDL particles 2e-221 rs12721030 1 GCST90501116 no MR -> candidate analysis
Polyunsaturated fatty acids 1e-206 rs525028 2 GCST90499302 no MR -> candidate analysis
…and 249 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 1225 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
hypoalphalipoproteinemia, primary, 2 0.856 established (curated) no MR -> candidate analysis
familial visceral amyloidosis 0.792 established (curated) no MR -> candidate analysis
Familial renal amyloidosis 0.792 established (curated) no MR -> candidate analysis
hypoalphalipoproteinemia, primary, 2, intermediate 0.849 established (curated) no MR -> candidate analysis
apolipoprotein A-I deficiency 0.79 established (curated) no MR -> candidate analysis
Abnormality of the cardiovascular system 0.649 established (curated) no MR -> candidate analysis
AApoAI amyloidosis 0.608 established (curated) no MR -> candidate analysis
Familial renal amyloidosis due to Apolipoprotein AI variant 0.608 established (curated) no MR -> candidate analysis
Severe intellectual disability and progressive spastic paraplegia 0.547 established (curated) no MR -> candidate analysis
Spastic paraplegia 0.547 established (curated) no MR -> candidate analysis
Hypercholesterolemia 0.488 common-variant locus MR: beta=-0.0445, p=0.0956 (cis)
metabolic disease 0.489 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.347 common-variant locus no MR -> candidate analysis
hypoalphalipoproteinemia, primary, 1 0.298 established (curated) no MR -> candidate analysis
metabolic syndrome 0.269 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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 0 known modulators (Apolipoprotein A-I)
gnomAD constraint pLI=3.2e-07, LOEUF=1.21 — LoF-tolerant
GWAS Catalog 289 unique SNPs / 742 rows
ClinVar 427 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx 2 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance