CausalSentinel

Protein Dossier — TREM2 (Triggering receptor expressed on myeloid cells 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
Non-cancer illness code self-reported: pernicious anaemia 0.642 0.216 0.00295 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.252 0.113 0.0258 Wald ratio 1 cis NA
Systolic blood pressure automated reading -0.0406 0.0216 0.06 Wald ratio 1 cis NA
Weight -0.0337 0.0186 0.07 Wald ratio 1 cis NA
Body mass index (BMI) -0.0381 0.0211 0.0705 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.126 0.077 0.103 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.062 0.0388 0.109 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb -0.426 0.267 0.111 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol -0.0943 0.0629 0.134 Wald ratio 1 cis NA
Eye problems or disorders: Cataract -0.212 0.145 0.143 Wald ratio 1 cis NA
Diagnoses - main ICD10: D25 Leiomyoma of uterus 0.222 0.153 0.147 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma 0.0764 0.0549 0.164 Wald ratio 1 cis NA
…and 39 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

51 association rows across 26 traits (39 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
TREM2 protein levels 3e-113 rs75932628 2 GCST90470960 no MR -> candidate analysis
Triggering receptor expressed on myeloid cells 2 levels 2e-96 rs143332484 1 GCST90249970 no MR -> candidate analysis
Circulating TREML2 levels 2e-44 rs62396354 1 GCST90859936 no MR -> candidate analysis
TREML2 protein levels 3e-42 rs113582625 5 GCST90470962 no MR -> candidate analysis
Alzheimer’s disease, proxy Alzheimer’s disease or related de 3e-38 rs75932628 6 GCST90704646 no MR -> candidate analysis
Alzheimer’s disease 3e-37 rs75932628 10 GCST90027158 no MR -> candidate analysis
Alzheimer’s disease or related dementias 7e-33 rs75932628 2 GCST90704647 no MR -> candidate analysis
Triggering receptor expressed on myeloid cells 2 level in Ch 7e-30 rs73427270 1 GCST90234514 no MR -> candidate analysis
Triggering receptor expressed on myeloid cells 2 (analyte X1 1e-25 rs143332484 1 GCST90422809 no MR -> candidate analysis
Alzheimer’s disease (late onset) 5e-24 rs75932628 3 GCST005549 no MR -> candidate analysis
Cerebrospinal fluid soluble TREM2 levels 7e-19 rs75932628 2 GCST90454420 no MR -> candidate analysis
Alzheimer’s disease (age of onset) 8e-17 rs75932628 2 GCST90093287 no MR -> candidate analysis
…and 14 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 611 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
Nasu-Hakola disease 0.887 established (curated) no MR -> candidate analysis
Alzheimer disease 0.858 common-variant locus no MR -> candidate analysis
frontotemporal dementia 0.666 established (curated) no MR -> candidate analysis
hereditary disease 0.672 established (curated) no MR -> candidate analysis
neurodegenerative disease 0.551 common-variant locus no MR -> candidate analysis
dementia 0.546 common-variant locus no MR -> candidate analysis
polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly 0.559 established (curated) no MR -> candidate analysis
late-onset Alzheimers disease 0.551 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.159 common-variant locus no MR -> candidate analysis
stroke disorder 0.057 common-variant locus no MR -> candidate analysis

Of the 10 rows above, 10 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 (Triggering receptor expressed on myeloid cells 2)
gnomAD constraint pLI=7.9e-07, LOEUF=1.27 — LoF-tolerant
GWAS Catalog 70 unique SNPs / 140 rows
ClinVar 202 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance