CausalSentinel

Protein Dossier — GRID2 (Glutamate receptor ionotropic, delta-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
Rheumatoid arthritis 0.181 0.0541 8.20e-04 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.117 0.0358 0.00102 Wald ratio 1 trans NA
Diagnoses - main ICD10: R35 Polyuria 0.303 0.108 0.00511 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.0933 0.0339 0.00593 Wald ratio 1 trans NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.138 0.0502 0.0061 Wald ratio 1 trans NA
Non-cancer illness code self-reported: bladder problem (not cancer) 0.225 0.0957 0.0186 Wald ratio 1 trans NA
Fractured bone site(s): Wrist -0.182 0.0779 0.0196 Wald ratio 1 trans NA
Diagnoses - main ICD10: I48 Atrial fibrillation and flutter 0.164 0.0731 0.0247 Wald ratio 1 trans NA
Weight 0.0174 0.00798 0.0297 Wald ratio 1 trans NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.133 0.0621 0.0324 Wald ratio 1 trans NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0461 0.0227 0.0425 Inverse variance weighted 2 trans NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.0461 0.0227 0.0425 Inverse variance weighted 2 trans NA
…and 103 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

103 association rows across 67 traits (64 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
Bone mineral density mean 5e-34 rs62311172 2 GCST90321120 no MR -> candidate analysis
CCER2 protein levels 8e-29 rs17021163 1 GCST90468563 no MR -> candidate analysis
Height 9e-28 rs1503211 2 GCST90245848 MR: beta=0.0174, p=0.129 (trans)
Smoking initiation 9e-25 rs1503212 9 GCST90243985 no MR -> candidate analysis
Body mass index 4e-19 rs6532412 9 GCST90662912 MR: beta=0.00729, p=0.42 (trans)
Educational attainment 9e-17 rs1972863 4 GCST90105038 no MR -> candidate analysis
Weight 7e-16 rs6532412 2 GCST90662910 MR: beta=0.0174, p=0.0297 (trans)
HPGDS protein levels 2e-14 rs10022274 2 GCST90469472 no MR -> candidate analysis
Educational attainment (MTAG) 4e-14 rs12503522 2 GCST006571 no MR -> candidate analysis
Educational attainment (years of education) 4e-13 rs12503522 2 GCST006442 no MR -> candidate analysis
Gut microbial network clusters (Salmon (at 1 year) x Any Bre 4e-13 rs74450133 1 GCST90569450 no MR -> candidate analysis
Smoking initiation (ever regular vs never regular) (MTAG) 6e-13 rs1160685 2 GCST007468 no MR -> candidate analysis
…and 55 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 2155 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
autosomal recessive spinocerebellar ataxia 18 0.845 established (curated) no MR -> candidate analysis
Autosomal recessive congenital cerebellar ataxia due to GRID2 deficiency 0.73 established (curated) no MR -> candidate analysis
hereditary disease 0.774 established (curated) no MR -> candidate analysis
diabetes mellitus 0.576 common-variant locus no MR -> candidate analysis
facial pain 0.562 common-variant locus no MR -> candidate analysis
obesity disorder 0.516 common-variant locus no MR -> candidate analysis
dementia 0.503 common-variant locus no MR -> candidate analysis
eye disorder 0.485 common-variant locus no MR -> candidate analysis
polyp of colon 0.485 common-variant locus no MR -> candidate analysis
smoking initiation 0.483 common-variant locus no MR -> candidate analysis
stricture 0.479 common-variant locus no MR -> candidate analysis
smoking cessation 0.477 common-variant locus no MR -> candidate analysis
intelligence 0.471 common-variant locus MR: beta=-0.0389, p=0.419 (trans)
colorectal carcinoma 0.406 common-variant locus no MR -> candidate analysis
alcohol drinking 0.406 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 (Glutamate (NMDA/AMPA/Kainate))
gnomAD constraint pLI=1, LOEUF=0.384 — LoF-INTOLERANT
GWAS Catalog 94 unique SNPs / 188 rows
ClinVar 408 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance