CausalSentinel

Protein Dossier — LCT (Lactase/phlorizin hydrolase)

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
Total cholesterol -0.0397 0.00516 1.36e-14 Wald ratio 1 cis 0.998
LDL cholesterol -0.0358 0.00541 3.62e-11 Wald ratio 1 cis 0.998
Forced vital capacity (FVC) -0.0191 0.003 2.27e-10 Wald ratio 1 cis 0.813
Body mass index (BMI) 0.0204 0.00366 2.59e-08 Wald ratio 1 cis 0.998
Forced expiratory volume in 1-second (FEV1) -0.0174 0.00317 4.22e-08 Wald ratio 1 cis 0.288
Height 0.0232 0.00438 1.20e-07 Wald ratio 1 cis 0.0218
Sleep duration 0.0137 0.00286 1.57e-06 Wald ratio 1 cis NA
Weight 0.0153 0.00323 2.29e-06 Wald ratio 1 cis NA
Potassium in urine 0.0171 0.00372 4.35e-06 Wald ratio 1 cis NA
Fasting insulin 0.0168 0.00438 1.32e-04 Wald ratio 1 cis NA
Body fat 0.0245 0.0067 2.58e-04 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0131 0.00374 4.66e-04 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

27 association rows across 22 traits (25 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
Lactase-phlorizin hydrolase levels (LCT.9017.58.3) 2e-69 rs1030766 1 GCST90241728 no MR -> candidate analysis
white blood cell count (WBC, maximum, inv-norm transformed) 9e-36 rs35940156 1 GCST90480723 no MR -> candidate analysis
DARS1 protein levels 7e-20 rs2304371 1 GCST90468947 no MR -> candidate analysis
Aspartate–tRNA ligase, cytoplasmic levels 8e-19 rs2304371 1 GCST90246480 no MR -> candidate analysis
Neutrophil count 1e-15 rs370868556 2 GCST90002398 no MR -> candidate analysis
Cholesterol esters in very large HDL 6e-14 rs3769012 1 GCST90501296 no MR -> candidate analysis
Physical function (baseline) 9e-14 rs56064699 1 GCST90565837 no MR -> candidate analysis
Cholesterol levels in very large HDL 2e-13 rs3769012 1 GCST90501294 no MR -> candidate analysis
Plasmacytoid Dendritic Cell Absolute Count 2e-13 rs2164210 1 GCST90001460 no MR -> candidate analysis
Cholesterol in Large HDL 6e-13 rs767569332 1 GCST90501134 no MR -> candidate analysis
Cholesteryl Esters in Large HDL 8e-13 rs767569332 1 GCST90501136 no MR -> candidate analysis
White blood cell count 2e-12 rs35837297 5 GCST009683 no MR -> candidate analysis
…and 10 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 846 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 lactase deficiency 0.805 established (curated) no MR -> candidate analysis
obesity disorder 0.587 common-variant locus no MR -> candidate analysis
lactose intolerance 0.512 common-variant locus no MR -> candidate analysis
morbid obesity 0.494 common-variant locus no MR -> candidate analysis
sleep disorder 0.435 common-variant locus MR: beta=0.052, p=0.252 (cis)
Sjogren syndrome 0.427 common-variant locus no MR -> candidate analysis
metabolic syndrome 0.413 common-variant locus no MR -> candidate analysis
cutaneous lupus erythematosus 0.409 common-variant locus no MR -> candidate analysis
nervous system disorder 0.385 common-variant locus no MR -> candidate analysis
polycystic ovary syndrome 0.363 common-variant locus no MR -> candidate analysis
hereditary disease 0.319 established (curated) no MR -> candidate analysis
essential tremor 0.306 common-variant locus no MR -> candidate analysis
Menorrhagia 0.251 common-variant locus no MR -> candidate analysis
Oligomenorrhea 0.251 common-variant locus no MR -> candidate analysis
Polymenorrhea 0.251 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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 (Lactase/phlorizin hydrolase)
gnomAD constraint pLI=1.8e-11, LOEUF=0.62 — LoF-tolerant
GWAS Catalog 64 unique SNPs / 128 rows
ClinVar 1007 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance