CausalSentinel

Protein Dossier — PARP16 (Protein mono-ADP-ribosyltransferase PARP16)

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
Serum creatinine (eGFRcrea) -0.00647 0.00139 3.44e-06 Wald ratio 1 trans NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.171 0.0475 3.19e-04 Wald ratio 1 trans NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt -0.13 0.0481 0.00666 Wald ratio 1 trans NA
Type 2 diabetes -0.0485 0.0193 0.0121 Wald ratio 1 trans NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.071 0.0288 0.0137 Wald ratio 1 trans NA
Fracture resulting from simple fall -0.0245 0.0103 0.018 Wald ratio 1 trans NA
Fractured or broken bones in last 5 years -0.0259 0.0122 0.033 Wald ratio 1 trans NA
Diagnoses - main ICD10: N20 Calculus of kidney and ureter 0.0814 0.0417 0.0512 Wald ratio 1 trans NA
Caudate volume 14.8 7.58 0.0515 Wald ratio 1 trans NA
Eye problems or disorders: Glaucoma 0.0576 0.03 0.0551 Wald ratio 1 trans NA
Neo-openness to experience -0.198 0.104 0.0559 Wald ratio 1 trans NA
Haemoglobin concentration -0.0185 0.00985 0.0603 Wald ratio 1 trans NA
…and 103 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

4 association rows across 4 traits (2 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
IGDCC4 protein levels 3e-20 rs56275228 1 GCST90469523 no MR -> candidate analysis
Left ventricular end systole inferoseptal wall thickness 1e-8 rs202032902 1 GCST90278508 no MR -> candidate analysis
Adolescent idiopathic scoliosis 9e-8 rs8027881 1 GCST006287 no MR -> candidate analysis
Left ventricular mass indexed by body surface area 6e-7 rs73468773 1 GCST90244710 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 45 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
Genu varum 0.351 common-variant locus no MR -> candidate analysis
Genu valgum 0.351 common-variant locus no MR -> candidate analysis
placental abruption 0.291 common-variant locus no MR -> candidate analysis
alcohol drinking 0.065 common-variant locus no MR -> candidate analysis
nephrotic syndrome 0.062 common-variant locus no MR -> candidate analysis
infectious meningitis 0.053 common-variant locus no MR -> candidate analysis
spondylolisthesis 0.053 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 0 known modulators (Protein mono-ADP-ribosyltransferase PARP16)
gnomAD constraint pLI=4.3e-10, LOEUF=1.19 — LoF-tolerant
GWAS Catalog 26 unique SNPs / 51 rows
ClinVar 77 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance