CausalSentinel

Protein Dossier — LHB (Lutropin subunit beta)

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
Creatinine (enzymatic) in urine 0.0322 0.00991 0.00117 Wald ratio 1 cis NA
Fractured or broken bones in last 5 years 0.0921 0.0295 0.00179 Wald ratio 1 cis NA
Age at menarche 0.0783 0.0258 0.0024 Wald ratio 1 cis NA
Alcohol intake frequency -0.0463 0.0153 0.0025 Wald ratio 1 cis NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone 0.271 0.0901 0.00266 Wald ratio 1 cis NA
Cancer code self-reported: prostate cancer 0.263 0.0941 0.00519 Wald ratio 1 cis NA
Fractured bone site(s): Other bones 0.105 0.0406 0.00957 Wald ratio 1 cis NA
Potassium in urine 0.027 0.0105 0.0103 Wald ratio 1 cis NA
Weight 0.0229 0.00914 0.0121 Wald ratio 1 cis NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate 0.25 0.1 0.0123 Wald ratio 1 cis NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms -0.26 0.111 0.019 Wald ratio 1 cis NA
Low grade serous ovarian cancer 0.516 0.224 0.021 Wald ratio 1 cis NA
…and 93 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

10 association rows across 9 traits (10 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
Luteinizing hormone levels 2e-187 rs3795052 1 GCST90248348 no MR -> candidate analysis
Human Chorionic Gonadotropin levels 2e-167 rs113572723 1 GCST90162185 no MR -> candidate analysis
Human Chorionic Gonadotropin levels (CGA.CGB.4914.10.1) 7e-100 rs3795047 2 GCST90241456 no MR -> candidate analysis
Lutropin subunit beta levels 2e-67 rs144948359 1 GCST90248342 no MR -> candidate analysis
Luteinizing hormone levels (CGA.LHB.2953.31.2) 7e-43 rs3795047 1 GCST90241825 no MR -> candidate analysis
LHB protein levels 9e-17 rs3795050 1 GCST90469767 no MR -> candidate analysis
Circulating LHB levels 7e-15 rs3795051 1 GCST90860326 no MR -> candidate analysis
Bioavailable testosterone levels 1e-10 rs6521 1 GCST90012103 no MR -> candidate analysis
Free testosterone levels 2e-8 rs3795047 1 GCST90239826 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 467 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
hypogonadotropic hypogonadism 23 with or without anosmia 0.779 established (curated) no MR -> candidate analysis
Leydig cell hypoplasia due to LHB deficiency 0.779 established (curated) no MR -> candidate analysis
hypogonadotropic hypogonadism 0.195 established (curated) no MR -> candidate analysis
uterine disorder 0.14 common-variant locus no MR -> candidate analysis

Of the 4 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 3 known modulators (Large envelope protein)
gnomAD constraint pLI=9e-05, LOEUF=1.72 — LoF-tolerant
GWAS Catalog 79 unique SNPs / 156 rows
ClinVar 109 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance