CausalSentinel

Protein Dossier — CRELD1 (Protein disulfide isomerase CRELD1)

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
Weight -0.0119 0.00225 1.17e-07 Wald ratio 1 cis 0.8
Height -0.011 0.00357 0.00209 Wald ratio 1 cis NA
Birth weight -0.0123 0.00402 0.00215 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.00603 0.00209 0.00395 Wald ratio 1 cis NA
Body mass index (BMI) -0.00722 0.00255 0.00466 Wald ratio 1 cis NA
Hip osteoarthritis -0.0762 0.0305 0.0123 Wald ratio 1 cis NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.0492 0.0198 0.0127 Wald ratio 1 cis NA
PGC cross-disorder traits 0.0315 0.013 0.0154 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.0231 0.0102 0.0244 Wald ratio 1 cis NA
Age at menopause 0.0823 0.0366 0.0244 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0283 0.0126 0.0251 Wald ratio 1 cis NA
Alcohol intake frequency -0.00761 0.00377 0.0434 Wald ratio 1 cis NA
…and 114 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

45 association rows across 29 traits (45 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
Cysteine-rich with EGF-like domain protein 1 levels 2e-1815 rs7650290 4 GCST90247154 no MR -> candidate analysis
Cysteine-rich with EGF-like domain protein 1 levels (CRELD1. 2e-556 rs7627326 2 GCST90240843 no MR -> candidate analysis
Serum levels of protein CRELD1 4e-267 rs2270894 1 GCST90089777 no MR -> candidate analysis
height (mean, inv-normal transformed) 5e-157 rs2270894 2 GCST90475362 no MR -> candidate analysis
Height (maximum, inv-normal transformed) 3e-148 rs2270894 2 GCST90475359 no MR -> candidate analysis
height (minimum, inv-normal transformed) 2e-126 rs2270894 2 GCST90475365 no MR -> candidate analysis
Cysteine-rich with EGF-like domain protein 1 level in Chroni 7e-94 rs73118372 1 GCST90238582 no MR -> candidate analysis
Height 2e-85 rs2270894 7 GCST90662911 MR: beta=-0.011, p=0.00209 (cis)
What is your height? (cm, inv-normal transformed) 4e-78 rs2270894 2 GCST90475368 no MR -> candidate analysis
Height (baseline) 2e-60 rs2270894 1 GCST90565843 no MR -> candidate analysis
Appendicular lean mass 1e-42 rs2270894 1 GCST90000025 no MR -> candidate analysis
Weight (mean, inv-normal transformed) 5e-40 rs2270894 2 GCST90476463 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 85 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
Jeffries-Lakhani neurodevelopmental syndrome 0.761 established (curated) no MR -> candidate analysis
hereditary disease 0.799 established (curated) no MR -> candidate analysis
ventricular septal defect 1 0.684 established (curated) no MR -> candidate analysis
congenital heart defects, multiple types, 4 0.684 established (curated) no MR -> candidate analysis
congenital heart disease 0.195 established (curated) no MR -> candidate analysis
Tetralogy of Fallot 0.195 established (curated) no MR -> candidate analysis
small cell lung carcinoma 0.05 common-variant locus no MR -> candidate analysis

Of the 7 rows above, 7 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=8.6e-11, LOEUF=0.934 — LoF-tolerant
GWAS Catalog 62 unique SNPs / 124 rows
ClinVar 313 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance