CausalSentinel

Protein Dossier — DLK1 (Protein delta homolog 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
Age at menarche -0.0635 0.0119 9.00e-08 Wald ratio 1 cis 0.858
Weight -0.0222 0.00423 1.55e-07 Wald ratio 1 cis 0.0065
Body mass index (BMI) -0.0188 0.00479 8.63e-05 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis -0.0646 0.0171 1.59e-04 Wald ratio 1 cis NA
Ovarian cancer 0.0941 0.0266 3.95e-04 Wald ratio 1 cis NA
Serum cystatin C (eGFRcys) -0.0138 0.00392 4.25e-04 Wald ratio 1 cis NA
High grade serous ovarian cancer 0.0911 0.0316 0.00394 Wald ratio 1 cis NA
Small vessel disease 0.212 0.0743 0.00435 Wald ratio 1 cis NA
Total cholesterol -0.0301 0.0106 0.00473 Wald ratio 1 cis NA
Pulse rate -0.0235 0.00845 0.00541 Wald ratio 1 cis NA
HDL cholesterol -0.0261 0.0099 0.00825 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine -0.0117 0.00459 0.011 Wald ratio 1 cis NA
…and 84 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

228 association rows across 124 traits (210 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
Circulating DLK1 levels 6e-1789 rs12881760 5 GCST90859946 no MR -> candidate analysis
DLK1/RGMB protein level ratio 9e-629 rs17577580 1 GCST90314493 no MR -> candidate analysis
DLK1/PIK3IP1 protein level ratio 4e-582 rs17577580 1 GCST90314492 no MR -> candidate analysis
DLK1/FAP protein level ratio 4e-576 rs17577580 1 GCST90314491 no MR -> candidate analysis
Protein delta homolog 1 levels 3e-362 rs12881545 4 GCST90248914 no MR -> candidate analysis
Platelet crit (UKB data field 30090) 2e-163 rs1555405 2 GCST90468096 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 2e-163 rs1555405 1 GCST90838671 no MR -> candidate analysis
Platelet count 4e-132 rs10873520 14 GCST90662907 no MR -> candidate analysis
DLK1 protein levels 1e-116 rs72698724 9 GCST90469003 no MR -> candidate analysis
Serum levels of protein SEMG2 4e-115 rs12881760 2 GCST90089376 no MR -> candidate analysis
platelet count (minimum, inv-norm transformed) 1e-112 rs12881545 3 GCST90476302 no MR -> candidate analysis
Serum levels of protein DLK1 3e-108 rs12881760 2 GCST90089461 no MR -> candidate analysis
…and 112 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 640 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
Abnormality of the skeletal system 0.703 common-variant locus no MR -> candidate analysis
osteoarthritis 0.618 common-variant locus MR: beta=-0.0646, p=1.59e-04 (cis)
type 2 diabetes mellitus 0.576 common-variant locus no MR -> candidate analysis
paternal uniparental disomy of chromosome 14 0.547 established (curated) no MR -> candidate analysis
Abnormality of refraction 0.514 common-variant locus no MR -> candidate analysis
central precocious puberty 0.471 established (curated) no MR -> candidate analysis
clonal hematopoiesis 0.451 common-variant locus no MR -> candidate analysis
myeloproliferative disorder 0.424 common-variant locus no MR -> candidate analysis
Hodgkins lymphoma 0.423 common-variant locus no MR -> candidate analysis
Abnormal nasolacrimal system morphology 0.364 common-variant locus no MR -> candidate analysis
hereditary disease 0.316 established (curated) no MR -> candidate analysis
cleft palate 0.3 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.224 common-variant locus no MR -> candidate analysis
Silver-Russell syndrome 0.228 established (curated) no MR -> candidate analysis
smoking initiation 0.23 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 (Protein delta homolog 1)
gnomAD constraint pLI=1, LOEUF=0.447 — LoF-INTOLERANT
GWAS Catalog 109 unique SNPs / 238 rows
ClinVar 135 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance