CausalSentinel

Protein Dossier — ITIH3 (Inter-alpha-trypsin inhibitor heavy chain H3)

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
Schizophrenia -0.192 0.029 3.53e-11 Wald ratio 1 cis NA
PGC cross-disorder traits -0.221 0.0336 5.13e-11 Wald ratio 1 cis NA
Body mass index (BMI) 0.0374 0.0066 1.44e-08 Wald ratio 1 cis NA
Bipolar disorder -0.322 0.0678 1.96e-06 Wald ratio 1 cis NA
Height -0.0383 0.0082 3.06e-06 Wald ratio 1 cis NA
Knee and hip osteoarthritis 0.26 0.0568 4.55e-06 Wald ratio 1 cis NA
Hip osteoarthritis 0.334 0.0799 2.94e-05 Wald ratio 1 cis NA
Pulse rate -0.0465 0.0116 6.47e-05 Wald ratio 1 cis NA
Weight 0.0211 0.00583 2.90e-04 Wald ratio 1 cis NA
Autism -0.257 0.0784 0.00104 Wald ratio 1 cis NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] -0.224 0.0692 0.00121 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb -0.189 0.0609 0.00195 Wald ratio 1 cis NA
…and 123 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

190 association rows across 140 traits (180 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
ITIH3/VCAM1 protein level ratio 1e-540 rs736408 1 GCST90315236 no MR -> candidate analysis
Inter-alpha-trypsin inhibitor heavy chain H3 levels 6e-463 rs2535629 3 GCST90247970 no MR -> candidate analysis
ITIH4 protein levels 1e-276 rs4687552 3 GCST90469651 no MR -> candidate analysis
Retinoblastoma-like protein 2 levels 1e-273 rs736408 3 GCST90249250 no MR -> candidate analysis
Height 4e-269 rs2535629 5 GCST90245848 MR: beta=-0.0383, p=3.06e-06 (cis)
Blood protein levels 1e-195 rs2535627 8 GCST006585 no MR -> candidate analysis
Circulating BLMH levels 8e-142 rs2710338 1 GCST90859929 no MR -> candidate analysis
Serum levels of protein ITIH3 2e-89 rs2535627 1 GCST90089692 no MR -> candidate analysis
Serum levels of protein RBL2 1e-82 rs736408 1 GCST90087529 no MR -> candidate analysis
ITIH3 protein levels 4e-71 rs736408 2 GCST90453267 no MR -> candidate analysis
Circulating PTS levels 7e-35 rs2710335 1 GCST90860729 no MR -> candidate analysis
Height (maximum, inv-normal transformed) 2e-34 rs4687552 1 GCST90479634 no MR -> candidate analysis
…and 128 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 181 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
Abnormality of the skeletal system 0.81 common-variant locus no MR -> candidate analysis
schizophrenia 0.708 common-variant locus MR: beta=-0.192, p=3.53e-11 (cis)
major depressive disorder 0.664 common-variant locus MR: beta=-0.131, p=0.0268 (cis)
bipolar disorder 0.666 common-variant locus MR: beta=-0.322, p=1.96e-06 (cis)
autism spectrum disorder 0.638 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.603 common-variant locus no MR -> candidate analysis
smoking initiation 0.472 common-variant locus no MR -> candidate analysis
risk-taking behaviour 0.469 common-variant locus no MR -> candidate analysis
obsessive-compulsive disorder 0.444 common-variant locus no MR -> candidate analysis
anorexia nervosa 0.444 common-variant locus no MR -> candidate analysis
Tourette syndrome 0.444 common-variant locus no MR -> candidate analysis
mental disorder 0.398 common-variant locus no MR -> candidate analysis
carpal tunnel syndrome 0.358 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.299 common-variant locus MR: beta=0.26, p=4.55e-06 (cis)
anxiety disorder 0.297 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 11 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=2.3e-23, LOEUF=1.01 — LoF-tolerant
GWAS Catalog 171 unique SNPs / 421 rows
ClinVar 165 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance