CausalSentinel

Protein Dossier — LPA (Apolipoprotein(a))

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 0.114 0.00844 1.09e-41 Wald ratio 1 cis NA
Coronary heart disease 0.252 0.0193 5.39e-39 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina 0.205 0.016 9.99e-38 Wald ratio 1 cis NA
Myocardial infarction 0.224 0.0211 2.37e-26 Wald ratio 1 cis NA
Total cholesterol 0.0986 0.0112 9.33e-19 Wald ratio 1 cis NA
LDL cholesterol 0.0935 0.0114 2.22e-16 Wald ratio 1 cis NA
Diagnoses - main ICD10: R07 Pain in throat and chest 0.0665 0.0146 5.29e-06 Wald ratio 1 cis NA
Serum creatinine (eGFRcrea) -0.00797 0.00183 1.37e-05 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.0681 0.023 0.0031 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0169 0.00587 0.00404 Wald ratio 1 cis NA
Large vessel disease 0.181 0.0722 0.0122 Wald ratio 1 cis NA
Diagnoses - main ICD10: R35 Polyuria 0.121 0.0498 0.0154 Wald ratio 1 cis NA
…and 99 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

2538 association rows across 929 traits (2489 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
Lipoprotein (a) levels 6e-22136 rs10455872 61 GCST011087 no MR -> candidate analysis
Triglyceride levels in chylomicrons and extremely large VLDL 8e-1032 rs10455872 6 GCST90501340 no MR -> candidate analysis
Total lipid levels in chylomicrons and extremely large VLDL 8e-929 rs10455872 6 GCST90501336 no MR -> candidate analysis
Cholesterol to Total Lipids in Chylomicrons and Extremely La 1e-891 rs10455872 3 GCST90501331 no MR -> candidate analysis
Triglycerides to Total Lipids in Chylomicrons and Extremely 1e-814 rs10455872 3 GCST90501341 no MR -> candidate analysis
Concentration of chylomicrons and extremely large VLDL parti 1e-813 rs10455872 7 GCST90501337 no MR -> candidate analysis
Phospholipid levels in chylomicrons and extremely large VLDL 1e-808 rs10455872 5 GCST90501338 no MR -> candidate analysis
Free cholesterol levels in chylomicrons and extremely large 1e-789 rs10455872 5 GCST90501334 no MR -> candidate analysis
Free Cholesterol to Total Lipids in Chylomicrons and Extreme 5e-750 rs10455872 3 GCST90501335 no MR -> candidate analysis
Cholesteryl Esters to Total Lipids in Chylomicrons and Extre 6e-722 rs10455872 3 GCST90501333 no MR -> candidate analysis
Cholesterol levels in chylomicrons and extremely large VLDL 2e-710 rs10455872 4 GCST90501330 no MR -> candidate analysis
Average diameter for VLDL particles 2e-649 rs10455872 5 GCST90501292 no MR -> candidate analysis
…and 917 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 576 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
cardiovascular disorder 0.909 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.894 common-variant locus no MR -> candidate analysis
myocardial infarction 0.879 common-variant locus MR: beta=0.224, p=2.37e-26 (cis)
heart disorder 0.899 common-variant locus no MR -> candidate analysis
Hypercholesterolemia 0.888 common-variant locus MR: beta=0.114, p=1.09e-41 (cis)
atherosclerosis 0.849 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.865 common-variant locus no MR -> candidate analysis
angina pectoris 0.868 common-variant locus no MR -> candidate analysis
myocardial ischemia 0.848 common-variant locus no MR -> candidate analysis
coronary atherosclerosis 0.85 common-variant locus no MR -> candidate analysis
peripheral vascular disease 0.851 common-variant locus no MR -> candidate analysis
metabolic disease 0.847 common-variant locus no MR -> candidate analysis
hyperlipidemia 0.84 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.801 common-variant locus no MR -> candidate analysis
congestive heart failure 0.839 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 2 known modulators (LPA mRNA)
gnomAD constraint pLI=2.1e-68, LOEUF=1.13 — LoF-tolerant
GWAS Catalog 271 unique SNPs / 690 rows
ClinVar 365 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx 3 clinical annotations across 2 drugs

Caveats declared by the tools

Sources

Provenance