CausalSentinel

Protein Dossier — DHX8 (ATP-dependent RNA helicase DHX8)

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
Diastolic blood pressure automated reading -0.0135 0.0035 1.20e-04 Wald ratio 1 trans NA
Non-cancer illness code self-reported: osteoporosis 0.0895 0.0251 3.62e-04 Wald ratio 1 trans NA
Sleep duration 0.00904 0.00267 7.11e-04 Wald ratio 1 trans NA
Height -0.0108 0.00417 0.00949 Wald ratio 1 trans NA
Total cholesterol 0.0164 0.00678 0.0154 Wald ratio 1 trans NA
Percent emphysema 0.0329 0.0138 0.0174 Wald ratio 1 trans NA
Urate 0.0183 0.0077 0.0176 Wald ratio 1 trans NA
LDL cholesterol 0.0168 0.00717 0.019 Wald ratio 1 trans NA
Lumbar spine bone mineral density -0.0289 0.0124 0.0196 Wald ratio 1 trans NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal -0.0718 0.031 0.0208 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis -0.101 0.044 0.022 Wald ratio 1 trans NA
Ferritin 0.0284 0.0133 0.0326 Wald ratio 1 trans NA
…and 88 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

31 association rows across 26 traits (27 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 CD300LG levels 2e-53 rs573043394 1 GCST90860606 no MR -> candidate analysis
LRRC37A2 protein levels 2e-19 rs191524289 1 GCST90469802 no MR -> candidate analysis
Hip shape mode 9 2e-15 rs2343132 1 GCST90482712 no MR -> candidate analysis
Standing height (UKB data field 50) 4e-14 rs4371196 1 GCST90468178 no MR -> candidate analysis
Aortic stenosis 5e-14 rs59386234 2 GCST90837546 no MR -> candidate analysis
HDL cholesterol levels x long total sleep time interaction ( 1e-13 rs75543966 1 GCST009368 no MR -> candidate analysis
Height (baseline) 8e-12 rs4371196 2 GCST90565843 no MR -> candidate analysis
Core binding factor acute myeloid leukemia 1e-11 rs12603053; rs3826413; rs9748005; rs11650719; rs7223638; rs4792997; rs7217897; rs12941944; rs7210301; rs1317254; rs1316956; rs4792900; rs7208294; rs4793000 2 GCST008413 no MR -> candidate analysis
Estimated glomerular filtration rate (creatinine, cystatin c 2e-11 rs34182830 1 GCST90428446 no MR -> candidate analysis
Alzheimer’s disease or family history of Alzheimer’s disease 9e-11 rs530555010 1 GCST90624094 no MR -> candidate analysis
Body mass index 3e-10 rs1728182 2 GCST90255621 no MR -> candidate analysis
Height 3e-10 rs9897859 2 GCST90245848 MR: beta=-0.0108, p=0.00949 (trans)
…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 294 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
congenital anomaly of kidney and urinary tract 0.426 established (curated) no MR -> candidate analysis
lens disorder 0.214 common-variant locus no MR -> candidate analysis
upper extremity fracture 0.21 common-variant locus no MR -> candidate analysis
duodenitis 0.187 common-variant locus MR: beta=0.0201, p=0.353 (trans)
high grade ovarian serous adenocarcinoma 0.117 common-variant locus no MR -> candidate analysis

Of the 5 rows above, 4 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 (ATP-dependent RNA helicase DHX8)
gnomAD constraint pLI=3.2e-06, LOEUF=0.584 — LoF-tolerant
GWAS Catalog 59 unique SNPs / 106 rows
ClinVar 240 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance