CausalSentinel

Protein Dossier — NEGR1 (Neuronal growth regulator 1)

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
Body mass index (BMI) -0.102 0.0163 3.92e-10 Wald ratio 1 cis NA
Sodium in urine 0.0901 0.016 1.88e-08 Wald ratio 1 cis NA
Weight -0.0759 0.0144 1.30e-07 Wald ratio 1 cis NA
Triglycerides -0.0791 0.0223 3.92e-04 Wald ratio 1 cis NA
Years of schooling -0.0878 0.027 0.00115 Wald ratio 1 cis NA
Body fat -0.1 0.0311 0.00129 Wald ratio 1 cis NA
Lung adenocarcinoma 0.538 0.175 0.00211 Wald ratio 1 cis NA
Age at menarche 0.115 0.0381 0.0026 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine 0.044 0.0156 0.00476 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.107 0.0419 0.0103 Wald ratio 1 cis NA
Alcohol intake frequency -0.0572 0.0241 0.0176 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.138 0.0586 0.019 Wald ratio 1 cis NA
…and 107 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

258 association rows across 133 traits (215 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
Educational attainment 2e-71 rs34305371 11 GCST90105038 no MR -> candidate analysis
Principal component-derived dietary pattern 1 3e-48 rs66495454 1 GCST90133006 no MR -> candidate analysis
Smoking initiation 1e-47 rs12737564 1 GCST90243985 no MR -> candidate analysis
Neuronal growth regulator 1 levels 2e-45 rs1194278 3 GCST90248636 no MR -> candidate analysis
Educational attainment (MTAG) 8e-41 rs34305371 3 GCST006571 no MR -> candidate analysis
Educational attainment (years of education) 1e-39 rs34305371 6 GCST006442 no MR -> candidate analysis
Insomnia 1e-31 rs1620977 21 GCST90131901 no MR -> candidate analysis
CAMSIS occupational score (MTAG) 9e-28 rs34305371 3 GCST90492678 no MR -> candidate analysis
Cognitive performance (MTAG) 5e-27 rs12128707 2 GCST006570 no MR -> candidate analysis
SIOPS occupational score (MTAG) 2e-26 rs34305371 3 GCST90492679 no MR -> candidate analysis
ISEI occupational score (MTAG) 2e-26 rs34305371 3 GCST90492677 no MR -> candidate analysis
Frailty (Factor 5 - Poorer Cognition) 3e-25 rs12128707 1 GCST90624051 no MR -> candidate analysis
…and 121 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 229 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
major depressive disorder 0.848 common-variant locus MR: beta=-0.215, p=0.141 (cis)
intelligence 0.865 common-variant locus MR: beta=-0.174, p=0.0438 (cis)
Abnormality of the skeletal system 0.855 common-variant locus no MR -> candidate analysis
obesity disorder 0.828 common-variant locus no MR -> candidate analysis
autism spectrum disorder 0.757 common-variant locus no MR -> candidate analysis
attention deficit-hyperactivity disorder 0.759 common-variant locus no MR -> candidate analysis
hair color 0.748 common-variant locus no MR -> candidate analysis
bipolar disorder 0.732 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.718 common-variant locus no MR -> candidate analysis
mathematical ability 0.725 common-variant locus no MR -> candidate analysis
schizophrenia 0.709 common-variant locus MR: beta=-0.1, p=0.167 (cis)
overnutrition 0.721 common-variant locus no MR -> candidate analysis
smoking initiation 0.685 common-variant locus no MR -> candidate analysis
smoking behavior 0.66 common-variant locus no MR -> candidate analysis
insomnia 0.66 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 12 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=1, LOEUF=0.415 — LoF-INTOLERANT
GWAS Catalog 182 unique SNPs / 446 rows
ClinVar 105 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance