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 |
| Diagnoses - main ICD10: I83 Varicose veins of lower extremities |
0.335 |
0.0817 |
4.19e-05 |
Wald ratio |
1 |
cis |
NA |
| Depressive symptoms |
0.0964 |
0.0301 |
0.00137 |
Wald ratio |
1 |
cis |
NA |
| Neuroticism |
0.0663 |
0.0241 |
0.00596 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: muscle or soft tissue injuries |
0.361 |
0.137 |
0.00828 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages |
0.395 |
0.156 |
0.0116 |
Wald ratio |
1 |
cis |
NA |
| Triglycerides |
0.0753 |
0.0307 |
0.0142 |
Wald ratio |
1 |
cis |
NA |
| Eye problems or disorders: Cataract |
0.179 |
0.0746 |
0.0162 |
Wald ratio |
1 |
cis |
NA |
| Sodium in urine |
0.038 |
0.016 |
0.0174 |
Wald ratio |
1 |
cis |
NA |
| Creatinine (enzymatic) in urine |
0.036 |
0.0155 |
0.0203 |
Wald ratio |
1 |
cis |
NA |
| Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis |
2.02 |
0.889 |
0.023 |
Wald ratio |
1 |
cis |
NA |
| Hearing difficulty or problems: Yes |
0.06 |
0.0264 |
0.0231 |
Wald ratio |
1 |
cis |
NA |
| Clear cell ovarian cancer |
-0.608 |
0.271 |
0.0248 |
Wald ratio |
1 |
cis |
NA |
| …and 107 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3323_37_1 |
LRP8 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
60 association rows across 53 traits (48 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 |
| Selenoprotein W levels |
1e-133 |
rs5177 |
2 |
GCST90249482 |
no MR -> candidate analysis |
| Cerebellar grey matter morphology (MOSTest) |
2e-72 |
rs11206127 |
1 |
GCST90728589 |
no MR -> candidate analysis |
| Low-density lipoprotein receptor-related protein 8 levels |
5e-48 |
rs2297663 |
4 |
GCST90248266 |
no MR -> candidate analysis |
| Vertex-wise cortical thickness |
1e-28 |
rs5174 |
1 |
GCST90095131 |
no MR -> candidate analysis |
| Whole brain restricted directional diffusion (multivariate a |
1e-26 |
rs5174 |
1 |
GCST90131905 |
no MR -> candidate analysis |
| Vertex-wise sulcal depth |
3e-26 |
rs5174 |
1 |
GCST90095129 |
no MR -> candidate analysis |
| Whole brain free water diffusion (multivariate analysis) |
3e-24 |
rs11206127 |
1 |
GCST90131906 |
no MR -> candidate analysis |
| Whole brain restricted isotropic diffusion (multivariate ana |
7e-21 |
rs3737983 |
1 |
GCST90131904 |
no MR -> candidate analysis |
| Educational attainment |
2e-20 |
rs10788951 |
1 |
GCST90105038 |
no MR -> candidate analysis |
| Cortical thickness |
1e-17 |
rs5174 |
1 |
GCST90091061 |
no MR -> candidate analysis |
| Serum levels of protein LRP8 |
4e-16 |
rs3737984 |
1 |
GCST90088315 |
no MR -> candidate analysis |
| Brain morphology (MOSTest) |
9e-15 |
rs5174 |
2 |
GCST90239729 |
no MR -> candidate analysis |
| …and 41 more traits (see JSON) |
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|
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 509 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 |
| myocardial infarction |
0.304 |
— |
established (curated) |
MR: beta=0.149, p=0.0301 (cis) |
| irritable bowel syndrome |
0.415 |
— |
common-variant locus |
no MR -> candidate analysis |
| risk-taking behaviour |
0.38 |
— |
common-variant locus |
no MR -> candidate analysis |
| schizophrenia |
0.267 |
— |
common-variant locus |
MR: beta=0.0964, p=0.179 (cis) |
| response to statin |
0.134 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 5 rows above, 3 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=0.2, LOEUF=0.527 — LoF-tolerant |
| GWAS Catalog |
64 unique SNPs / 128 rows |
| ClinVar |
175 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 509 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — No ChEMBL target for ‘LRP8’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 175 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 53 traits by best p-value, aggregated from 60 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/Q14114 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000157193/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/LRP8 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/LRP8 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=LRP8%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/LRP8 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:37:40 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none