CausalSentinel

Protein Dossier — DKK2 (Dickkopf-related protein 2)

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
Ovarian cancer 0.117 0.0369 0.00146 Wald ratio 1 cis NA
Birth weight -0.0289 0.0102 0.00446 Wald ratio 1 cis NA
High grade serous ovarian cancer 0.124 0.0443 0.00493 Wald ratio 1 cis NA
Weight -0.0139 0.00553 0.0118 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0379 0.0168 0.0243 Wald ratio 1 cis NA
Body mass index (BMI) -0.0137 0.00626 0.029 Wald ratio 1 cis NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus -0.133 0.0634 0.0356 Wald ratio 1 cis NA
Eczema 0.104 0.0521 0.0458 Wald ratio 1 cis NA
Cough on most days -0.0642 0.0341 0.0598 Wald ratio 1 cis NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.123 0.0662 0.0625 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis -0.123 0.067 0.0668 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis 0.0836 0.0463 0.0709 Wald ratio 1 cis NA
…and 64 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

40 association rows across 29 traits (20 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
Serum levels of protein DKK2 1e-164 rs114497723 1 GCST90089488 no MR -> candidate analysis
Blood protein levels 2e-83 rs77571736 1 GCST006585 no MR -> candidate analysis
Male-pattern baldness 2e-33 rs76067940 7 GCST007020 no MR -> candidate analysis
Balding type 1 2e-25 rs76067940 2 GCST007038 no MR -> candidate analysis
Circulating CST6 levels 3e-19 rs7663915 2 GCST90860620 no MR -> candidate analysis
CST6 protein levels 5e-19 rs7663915 1 GCST90468896 no MR -> candidate analysis
Circulating DSG4 levels 3e-11 rs10023574 1 GCST90860253 no MR -> candidate analysis
Vertex-wise sulcal depth 6e-11 rs76067940 1 GCST90095129 no MR -> candidate analysis
Vaginal microbiome relative abundance (s_Lactobacillus mulie 3e-10 rs75042393 2 GCST90027014 no MR -> candidate analysis
Total PHF-tau (SNP x SNP interaction) 3e-10 rs979775 x rs11933230 1 GCST010340 no MR -> candidate analysis
Anxiety x Caesarean-section interaction 1e-9 rs13137764 1 GCST90275370 no MR -> candidate analysis
Cortical surface area 2e-8 rs76067940 1 GCST90091060 no MR -> candidate analysis
…and 17 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 783 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
androgenetic alopecia 0.747 common-variant locus no MR -> candidate analysis
alopecia 0.64 common-variant locus no MR -> candidate analysis
benign prostatic hyperplasia 0.523 common-variant locus no MR -> candidate analysis
Abnormal nasolacrimal system morphology 0.52 common-variant locus no MR -> candidate analysis
intestinal obstruction 0.52 common-variant locus no MR -> candidate analysis
Hyperhidrosis 0.51 common-variant locus no MR -> candidate analysis
Anxiety 0.501 common-variant locus MR: beta=-0.0847, p=0.151 (cis)
cesarean section 0.501 common-variant locus no MR -> candidate analysis
respiratory tract infectious disorder 0.405 common-variant locus no MR -> candidate analysis
asthma 0.405 common-variant locus no MR -> candidate analysis
poisoning 0.393 common-variant locus no MR -> candidate analysis
vitiligo 0.346 common-variant locus no MR -> candidate analysis
multiple sclerosis 0.311 common-variant locus no MR -> candidate analysis
placenta praevia 0.246 common-variant locus no MR -> candidate analysis
benign neoplasm of eye 0.221 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=0.47, LOEUF=0.648 — LoF-tolerant
GWAS Catalog 33 unique SNPs / 51 rows
ClinVar 50 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance