CausalSentinel

Protein Dossier — GDF15 (Growth/differentiation factor 15)

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
Body mass index (BMI) 0.0243 0.00486 5.71e-07 Wald ratio 1 cis NA
Weight 0.0194 0.00429 5.89e-06 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.15 0.0487 0.00203 Wald ratio 1 cis NA
Low grade serous ovarian cancer -0.273 0.0991 0.00584 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.0108 0.00399 0.00671 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol 0.0344 0.0127 0.00682 Wald ratio 1 cis NA
Fractured bone site(s): Wrist 0.0822 0.032 0.0101 Wald ratio 1 cis NA
Non-cancer illness code self-reported: chronic obstructive airways disease or copd 0.176 0.0702 0.0123 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pernicious anaemia 0.18 0.0752 0.0167 Wald ratio 1 cis NA
Cough on most days -0.0618 0.0264 0.0191 Wald ratio 1 cis NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis -0.0751 0.0339 0.0268 Wald ratio 1 cis NA
Alcohol intake frequency 0.0159 0.00718 0.0271 Wald ratio 1 cis NA
…and 71 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

48 association rows across 28 traits (43 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 GDF15 levels 1e-851 rs1054221 3 GCST90859943 no MR -> candidate analysis
Growth differentiation factor-15 levels 3e-250 rs1227734 5 GCST90011998 no MR -> candidate analysis
Growth/differentiation factor 15 levels 3e-175 rs75347775 7 GCST90247708 no MR -> candidate analysis
Serum levels of protein GDF15 1e-102 rs1058587 2 GCST90088672 no MR -> candidate analysis
GDF15 protein levels 2e-54 rs113700483 5 GCST90469321 no MR -> candidate analysis
Severity of nausea and vomiting of pregnancy 2e-41 rs16982345 1 GCST005929 no MR -> candidate analysis
Growth/differentiation factor 15 levels (GDF15.4374.45.2) 1e-34 rs1227734 1 GCST90241351 no MR -> candidate analysis
Cerebrospinal fluid protein GDF15 levels 3e-27 rs62122429 1 GCST90944768 no MR -> candidate analysis
Growth differentiation factor-15 levels (conditioned on rs88 1e-22 rs1059519 2 GCST005712 no MR -> candidate analysis
LRRC25 protein levels 7e-22 rs62122428 1 GCST90469801 no MR -> candidate analysis
Hyperemesis gravidarum 2e-19 rs16982345 1 GCST005930 no MR -> candidate analysis
mean corpuscular volume (MCV, minimum, inv-norm transformed) 4e-15 rs8110358 1 GCST90479677 no MR -> candidate analysis
…and 16 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 1595 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
hyperemesis gravidarum 0.703 established (curated) no MR -> candidate analysis
coffee consumption 0.678 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.251 common-variant locus no MR -> candidate analysis
obesity disorder 0.079 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.037 common-variant locus no MR -> candidate analysis
systemic lupus erythematosus 0.048 common-variant locus no MR -> candidate analysis

Of the 6 rows above, 6 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 (Growth/differentiation factor 15)
gnomAD constraint pLI=0.00013, LOEUF=1.9 — LoF-tolerant
GWAS Catalog 189 unique SNPs / 505 rows
ClinVar 71 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance