CausalSentinel

Protein Dossier — NR1D2 (Nuclear receptor subfamily 1 group D member 2)

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
Diagnoses - main ICD10: K80 Cholelithiasis 0.285 0.0736 1.09e-04 Wald ratio 1 trans NA
Total cholesterol -0.107 0.0283 1.61e-04 Wald ratio 1 trans NA
Bipolar disorder 0.454 0.133 6.66e-04 Wald ratio 1 trans NA
LDL cholesterol -0.0971 0.0293 9.36e-04 Wald ratio 1 trans NA
Systemic lupus erythematosus 0.837 0.266 0.00168 Wald ratio 1 trans NA
Vascular or heart problems diagnosed by doctor: Angina 0.175 0.066 0.00803 Wald ratio 1 trans NA
Serum creatinine (eGFRcrea) -0.0128 0.00491 0.00909 Wald ratio 1 trans NA
Diagnoses - main ICD10: I30 Acute pericarditis 0.94 0.36 0.00909 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.138 0.0542 0.0108 Wald ratio 1 trans NA
Fractured bone site(s): Arm 0.264 0.109 0.0157 Wald ratio 1 trans NA
Knee osteoarthritis 0.361 0.153 0.0182 Wald ratio 1 trans NA
Diagnoses - main ICD10: B37 Candidiasis 0.8 0.342 0.0192 Wald ratio 1 trans NA
…and 109 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

57 association rows across 39 traits (49 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
Height 2e-51 rs1112195 4 GCST90245848 no MR -> candidate analysis
Intelligence 2e-17 rs6550835 7 GCST006250 MR: beta=-0.11, p=0.133 (trans)
Fluid intelligence score (baseline) 3e-17 rs10865793 1 GCST90565842 no MR -> candidate analysis
Attention deficit hyperactivity disorder or autism spectrum 6e-17 rs6550835 2 GCST90134330 no MR -> candidate analysis
Cognitive performance 4e-16 rs6550835 1 GCST006572 no MR -> candidate analysis
Personality traits or cognitive traits (multivariate analysi 7e-16 rs954734 1 GCST90270074 no MR -> candidate analysis
Cognitive aspects of educational attainment 8e-16 rs6550835 1 GCST90011875 no MR -> candidate analysis
Intelligence (MTAG) 2e-15 rs7431278 3 GCST005316 no MR -> candidate analysis
KLRB1 protein levels 1e-14 rs4619736 1 GCST90469709 no MR -> candidate analysis
Fluid intelligence 3e-14 rs6550835 3 GCST90832687 no MR -> candidate analysis
Highest math class taken (MTAG) 9e-13 rs5001573 1 GCST006568 no MR -> candidate analysis
General cognitive ability 1e-12 rs954734 2 GCST006269 no MR -> candidate analysis
…and 27 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 737 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
mathematical ability 0.62 common-variant locus no MR -> candidate analysis
intelligence 0.469 common-variant locus MR: beta=-0.11, p=0.133 (trans)
escherichia coli infection 0.462 common-variant locus no MR -> candidate analysis
familial atrioventricular septal defect 0.426 established (curated) no MR -> candidate analysis
pneumonia 0.425 common-variant locus no MR -> candidate analysis
fungal lung infectious disease 0.425 common-variant locus no MR -> candidate analysis
allergic asthma 0.395 common-variant locus no MR -> candidate analysis
liver disorder 0.339 common-variant locus no MR -> candidate analysis
schizophrenia 0.313 common-variant locus no MR -> candidate analysis
smoking initiation 0.238 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.199 common-variant locus no MR -> candidate analysis
autism spectrum disorder 0.199 common-variant locus no MR -> candidate analysis
uterine corpus leiomyoma 0.137 common-variant locus no MR -> candidate analysis
placenta praevia 0.12 common-variant locus no MR -> candidate analysis
Uterine leiomyoma 0.117 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 (Nuclear receptor subfamily 1 group D member 2)
gnomAD constraint pLI=0.0052, LOEUF=0.668 — LoF-tolerant
GWAS Catalog 58 unique SNPs / 116 rows
ClinVar 111 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance