CausalSentinel

Protein Dossier — CFHR1 (Complement factor H-related protein 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
Forearm bone mineral density 0.0496 0.0173 0.00406 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma -0.0658 0.0252 0.00908 Wald ratio 1 cis NA
Diagnoses - main ICD10: B37 Candidiasis 0.271 0.105 0.0095 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis -0.0599 0.0242 0.0135 Wald ratio 1 cis NA
IgA nephropathy 0.228 0.0982 0.0202 Wald ratio 1 cis NA
Clear cell ovarian cancer 0.108 0.0466 0.0205 Wald ratio 1 cis NA
Lung adenocarcinoma 0.0649 0.0282 0.0214 Wald ratio 1 cis NA
Systemic lupus erythematosus 0.118 0.0519 0.0232 Wald ratio 1 cis NA
Alzheimer’s disease 0.0422 0.0186 0.0235 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.00523 0.00233 0.025 Wald ratio 1 cis NA
Fractured bone site(s): Wrist -0.0474 0.0213 0.026 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia -0.0399 0.0181 0.0275 Wald ratio 1 cis NA
…and 95 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

148 association rows across 93 traits (144 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
Complement factor H-related protein 1 levels 4e-993 rs67908756 4 GCST90246993 no MR -> candidate analysis
Alpha-N-acetylglucosaminidase levels 2e-428 rs67908756 1 GCST90248587 no MR -> candidate analysis
Age-related macular degeneration (MTAG) 6e-414 rs7542235 1 GCST010284 no MR -> candidate analysis
CFHR5 plasma levels 3e-396 rs10737681 1 GCST90244658 no MR -> candidate analysis
Blood protein levels 7e-381 rs57809726 30 GCST006585 no MR -> candidate analysis
Leucine-rich repeat-containing protein 19 levels (LRRC19.701 1e-307 rs7519758 2 GCST90241776 no MR -> candidate analysis
Age-related macular degeneration or COVID-19 critical illnes 4e-291 rs60642321 1 GCST90250832 no MR -> candidate analysis
Age-related macular degeneration or COVID-19 infection (MTAG 8e-291 rs60642321 1 GCST90250834 no MR -> candidate analysis
Age-related macular degeneration or COVID-19 hospitalization 9e-291 rs60642321 1 GCST90250833 no MR -> candidate analysis
CFHR4 protein levels 3e-268 rs184080912 4 GCST90468727 no MR -> candidate analysis
Serum levels of protein CFHR4 2e-246 rs7413610 1 GCST90089450 no MR -> candidate analysis
Serum levels of protein HPX 4e-228 rs6679884 1 GCST90088060 no MR -> candidate analysis
…and 81 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 301 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
age-related macular degeneration 0.426 established (curated) no MR -> candidate analysis
C3 glomerulonephritis 0.608 established (curated) no MR -> candidate analysis
dense deposit disease 0.608 established (curated) no MR -> candidate analysis
atypical hemolytic-uremic syndrome with I factor anomaly 0.559 established (curated) no MR -> candidate analysis
degeneration of macula and posterior pole 0.575 common-variant locus no MR -> candidate analysis
macular degeneration 0.553 common-variant locus no MR -> candidate analysis
COVID-19 0.345 common-variant locus no MR -> candidate analysis
chronic kidney disease 0.265 established (curated) no MR -> candidate analysis
meningococcal infection 0.252 common-variant locus no MR -> candidate analysis
retinal disorder 0.24 common-variant locus no MR -> candidate analysis
wet macular degeneration 0.193 common-variant locus no MR -> candidate analysis
cerebral amyloid angiopathy, APP-related 0.195 established (curated) no MR -> candidate analysis
IgA glomerulonephritis 0.105 common-variant locus no MR -> candidate analysis
kidney disorder 0.066 established (curated) no MR -> candidate analysis

Of the 14 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=3.6e-06, LOEUF=1.03 — LoF-tolerant
GWAS Catalog 136 unique SNPs / 328 rows
ClinVar 189 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance