CausalSentinel

Protein Dossier — CHRDL2 (Chordin-like 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
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal 0.267 0.0607 1.06e-05 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.234 0.0704 8.93e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.19 0.0632 0.00273 Wald ratio 1 cis NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.151 0.0631 0.0168 Wald ratio 1 cis NA
Red blood cell count 0.0241 0.0103 0.0188 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0625 0.0273 0.0219 Wald ratio 1 cis NA
Mean cell haemoglobin concentration -0.034 0.015 0.0232 Wald ratio 1 cis NA
Mean cell volume -0.268 0.12 0.0257 Wald ratio 1 cis NA
Non-cancer illness code self-reported: enlarged prostate -0.212 0.1 0.0343 Wald ratio 1 cis NA
Small vessel disease 0.39 0.191 0.0406 Wald ratio 1 cis NA
Age at menopause 0.187 0.0935 0.0455 Wald ratio 1 cis NA
Diagnoses - main ICD10: K80 Cholelithiasis 0.109 0.0586 0.0633 Wald ratio 1 cis NA
…and 83 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 26 traits (35 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 CHRDL2 levels 6e-382 rs574672574 1 GCST90860378 no MR -> candidate analysis
Circulating BMP4 levels 8e-113 rs574672574 2 GCST90859714 no MR -> candidate analysis
BMP4 protein levels 1e-109 rs574672574 1 GCST90468453 no MR -> candidate analysis
Height 9e-93 rs2000924 1 GCST90245848 no MR -> candidate analysis
Chordin-like protein 2 levels 6e-86 rs551789974 1 GCST90247151 no MR -> candidate analysis
Serum levels of protein CHRDL2 1e-85 rs61389091 1 GCST90089279 no MR -> candidate analysis
Blood protein levels 1e-47 rs11236228 2 GCST006585 no MR -> candidate analysis
Bone morphogenetic protein 4 levels 1e-35 rs551789974 1 GCST90246719 no MR -> candidate analysis
Bone morphogenetic protein 6 levels 6e-34 rs535025308 1 GCST90246720 no MR -> candidate analysis
Serum levels of protein BMP6 6e-34 rs76136269 1 GCST90090203 no MR -> candidate analysis
BMP6 protein levels 6e-32 rs11607100 1 GCST90468454 no MR -> candidate analysis
Circulating BMP6 levels 8e-32 rs11607100 1 GCST90859741 no MR -> candidate analysis
…and 14 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 86 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
colonic neoplasm 0.711 common-variant locus no MR -> candidate analysis
polyp of colon 0.712 common-variant locus no MR -> candidate analysis
colorectal cancer 0.68 common-variant locus no MR -> candidate analysis
benign colon neoplasm 0.625 common-variant locus MR: beta=0.267, p=1.06e-05 (cis)
uterine prolapse 0.596 common-variant locus no MR -> candidate analysis
anus neoplasm 0.579 common-variant locus MR: beta=0.267, p=1.06e-05 (cis)
rectal neoplasm 0.579 common-variant locus no MR -> candidate analysis
pernicious anemia 0.39 common-variant locus no MR -> candidate analysis
contracture 0.389 common-variant locus no MR -> candidate analysis
Hallux valgus 0.365 common-variant locus no MR -> candidate analysis
alcohol drinking 0.101 common-variant locus no MR -> candidate analysis
pelvic organ prolapse 0.1 common-variant locus no MR -> candidate analysis
atrial fibrillation 0.065 common-variant locus no MR -> candidate analysis
prolapse of female genital organ 0.05 common-variant locus no MR -> candidate analysis

Of the 14 rows above, 12 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=4.1e-11, LOEUF=0.98 — LoF-tolerant
GWAS Catalog 68 unique SNPs / 136 rows
ClinVar 77 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance